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Handbook for young people with diabetes

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What is <strong>diabetes</strong>?<br />

Self-monitoring<br />

of blood glucose<br />

Insulin therapy<br />

General principles<br />

<strong>for</strong> changing doses<br />

Injection areas<br />

and methods<br />

Nutrition<br />

Physical exercise<br />

Hypoglycaemia<br />

and ketoacidosis<br />

<strong>Handbook</strong><br />

<strong>for</strong> <strong>young</strong> <strong>people</strong><br />

<strong>with</strong> <strong>diabetes</strong><br />

edited by Riccardo Bonfanti, Andrea Rigamonti and Giulio Frontino<br />

<strong>with</strong> the coordination of Franco Meschi<br />

Long-term<br />

complications<br />

Insulin pump<br />

Facing or clashing<br />

<strong>with</strong> <strong>diabetes</strong><br />

Special situations<br />

The future of <strong>people</strong> <strong>with</strong><br />

<strong>diabetes</strong><br />

Glossary


<strong>Handbook</strong><br />

<strong>for</strong> <strong>young</strong> <strong>people</strong><br />

<strong>with</strong> <strong>diabetes</strong><br />

edited by Riccardo Bonfanti, Andrea Rigamonti and Giulio Frontino<br />

<strong>with</strong> the coordination of Franco Meschi


With the contribution of:<br />

Roseila Battaglino, Clara Bonura e Valeria Favalli


Index<br />

Preface 5<br />

Introduction 7<br />

What is <strong>diabetes</strong>? 9<br />

Self-monitoring of blood glucose 19<br />

Insulin therapy 26<br />

Injection areas and methods 37<br />

Nutrition 42<br />

Physical exercise 52<br />

Hypoglycaemia and ketoacidosis 55<br />

Long-term complications 66<br />

Insulin pump 72<br />

Facing or clashing <strong>with</strong> <strong>diabetes</strong> 95<br />

Particular situations 98<br />

The future of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong> 106<br />

Index


Preface<br />

The “SOStegno 70” Association was established in December<br />

of 2001 by a group of parents of children and <strong>young</strong> <strong>people</strong><br />

<strong>with</strong> <strong>diabetes</strong> who felt the need <strong>for</strong> a point of reference and an<br />

opportunity to exchange in<strong>for</strong>mation and experiences.<br />

When you receive a diagnosis of <strong>diabetes</strong> <strong>for</strong> your child, you<br />

feel lost, helpless, and unjustified guilt often arises. However,<br />

you immediately realise that there is no time to give in to your<br />

anxieties and insecurities because this would affect the child<br />

you have to protect and safeguard. It is a difficult time from<br />

a psychological point of view, and being able to rely on other<br />

<strong>people</strong> who are going through a similar experience is of great<br />

help. In fact, parents <strong>with</strong> a high level of experience may, <strong>with</strong>out<br />

in any way substituting the indispensable contribution of their<br />

diabetologist, provide valuable suggestions <strong>for</strong> the daily practical<br />

management of the disease.<br />

For <strong>people</strong> involved in different activities, beginning to live <strong>with</strong><br />

<strong>diabetes</strong> means quickly acquiring a number of medical skills which<br />

are essential to ensure optimal glycaemic control and to help the<br />

child to become independent in the management of the disease.<br />

This handbook was there<strong>for</strong>e created as a reference tool <strong>for</strong> <strong>young</strong><br />

<strong>people</strong> <strong>with</strong> <strong>diabetes</strong>.<br />

One of the main purposes of SOStegno 70 to give support to<br />

<strong>young</strong> <strong>people</strong> <strong>with</strong> <strong>diabetes</strong> and their families in any <strong>diabetes</strong><br />

centre in the country, through continuous practical training and<br />

in<strong>for</strong>mation to ensure an ever improving quality of life and care.<br />

These activities are provided in collaboration <strong>with</strong> the Doctors of<br />

the Paediatric Clinics in Milan in which the Association has its<br />

offices – at the Pediatric Endocrinology and Diabetology Clinic at<br />

the San Raffaele Scientific Institute of Milano (a regional centre of<br />

reference in the field), and at its offices in Brescia at the “Spedali<br />

Civili” Hospital.


Preface<br />

The Association carries out general activities, such as the purchase<br />

of innovative monitoring and therapeutic devices, the organisation<br />

of age-specific <strong>diabetes</strong> camps – <strong>with</strong> the aim to provide education<br />

regarding an independent and aware management of their therapy<br />

– the establishment of scholarships <strong>for</strong> promising <strong>young</strong> doctors,<br />

public and institutional awareness in regard to this condition, and<br />

local activities specifically focused on the territory’s needs.<br />

All these initiatives are not only possible thanks to the funds<br />

raised, but above all because of the involvement and commitment<br />

of the Association’s volunteers.<br />

It is they, the volunteers, who are the backbone of SOStegno 70,<br />

<strong>with</strong> their constant presence in the hospitals, alongside families<br />

suffering the impact of the disease, and through their relationships<br />

<strong>with</strong> Doctors. They organise side events, providing effective<br />

operational support.<br />

In<strong>for</strong>mation, responsibility and therapeutic quality – <strong>with</strong> the<br />

children and their families at the heart of the matter: this is<br />

SOStegno 70.<br />

Patrizia Pappini<br />

SOStegno 70<br />

Insieme ai ragazzi diabetici Onlus<br />

www.sostegno70.org<br />

70 because this is the ideal blood glucose value of a healthy person.<br />

70 like hope, as a value that parents also wish <strong>for</strong> their children, in<br />

the not too distant future.


Introduction<br />

“When I was a child I became diabetic. I would take the<br />

urine glucose test 2-3 times a day and, occasionally, I would<br />

measure my blood sugar level at <strong>diabetes</strong> check-ups. By<br />

doing this I was considered a good boy <strong>with</strong> well-controlled<br />

<strong>diabetes</strong>. But now, if I test my blood glucose 5-6 times a day<br />

and the inject insulin 4-5 times a day, I am not considered a<br />

good patient.” This is what one of our diabetic “<strong>for</strong>mer child<br />

patients” told us. He is now a <strong>young</strong> adult <strong>with</strong> a good career,<br />

<strong>with</strong> a good position in society.<br />

Looking back at the previous edition of this handbook, I<br />

realise that it is true; we ask more and more from our <strong>young</strong><br />

patients, but <strong>for</strong>tunately, technology has allowed us to make<br />

ever increasing progress in relation to the difficulties they face<br />

on a daily basis.<br />

Without doubt we require a lot of blood glucose tests, often<br />

too many, but the technical quality of blood glucose monitors<br />

and their multiple benefits have enabled us to achieve a<br />

precision and accuracy that was unthinkable a few years ago.<br />

More and more frequently the use of glucose sensors allows<br />

us to identify and resolve situations that are often difficult.<br />

The use of new types of insulin, and especially the<br />

increasingly widespread use of insulin pumps, are<br />

revolutionising the approach towards <strong>diabetes</strong>, allowing us to<br />

nearly simulate the physiological secretion of insulin.<br />

Recent improvements in <strong>diabetes</strong> management have been<br />

instrumental in getting decreasing values of HbA1c.<br />

Furthermore, <strong>diabetes</strong> complications have become almost an<br />

exceptional event in the lives of our <strong>young</strong> adults, even after<br />

many years of suffering from the disease.


Introduzione<br />

Introduction<br />

A more scientific approach to nutrition and the invaluable<br />

contributions of psychologists have proven to be fundamental<br />

in a challenging period such as the of adolescence.<br />

In recent years, many <strong>young</strong> doctors have achieved their<br />

specialisations in our group. They are now operating<br />

throughout the country <strong>with</strong> extreme competence, allowing<br />

close cooperation, there<strong>for</strong>e providing significant benefits <strong>for</strong><br />

their patients.<br />

This presentation allows me to once again thank the youths<br />

and their parents. Their daily activities have allowed us to<br />

accomplish achievements that our group feels very proud of.<br />

We know that the sacrifices we ask <strong>for</strong> means securing their<br />

future.<br />

Giuseppe Chiumello<br />

Paediatric Endocrinology and Diabetes Centre<br />

San Raffaele Scientific Institute<br />

Milano, Italy


What is <strong>diabetes</strong>?<br />

What is <strong>diabetes</strong>?<br />

( 9


What is <strong>diabetes</strong>?<br />

The purpose of this handbook is to provide useful in<strong>for</strong>mation<br />

to <strong>young</strong> <strong>people</strong> <strong>with</strong> <strong>diabetes</strong> and their families, in order to<br />

promote proper <strong>diabetes</strong> self-management<br />

Diabetes is in your hands!<br />

A history of <strong>diabetes</strong><br />

10 )<br />

Diabetes mellitus is an ancient disease. It was already known about thirty-five<br />

centuries ago, and traces have been found in the history of medicine.<br />

The words “<strong>diabetes</strong> mellitus” derive from Greek and mean “siphon” or<br />

“fountain” and “sweet as honey” respectively, referring to the presence of sugar in<br />

the large quantities of urine. The Egyptians mentioned <strong>diabetes</strong> in a papyrus dating<br />

back to 1550 BC. Traditional Indian medicine, which dates back to the fifth century<br />

AD, mentions two types of <strong>diabetes</strong>, one that occurs in underweight <strong>people</strong> of all<br />

ages and the other that is common in overweight <strong>people</strong>. For a long time in the history<br />

of medicine it was thought that <strong>diabetes</strong> was a disease of the kidneys – in 1679, an<br />

English physician called Thomas Willis described the urine of patients <strong>with</strong> <strong>diabetes</strong> as<br />

“beautifully sweet”. About a hundred years later, a physician from Ox<strong>for</strong>d first observed<br />

that there were high levels of sugar in the blood of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong>. This led<br />

him to suppose that the sugar was lost in the urine be<strong>for</strong>e being used.<br />

The key to understanding the real cause of <strong>diabetes</strong> was only discovered in 1889.<br />

In that year, Paul Langerhans discovered that there were groups of cells that were not<br />

associated <strong>with</strong> other pancreatic digestive processes <strong>with</strong>in the pancreatic tissue. He<br />

also noticed that if these cells were damaged, a situation similar to <strong>diabetes</strong> developed.<br />

These cells have since been called “Islets of Langerhans” and it led to the opinion<br />

that they were able to produce a chemical (hormone) capable of preventing <strong>diabetes</strong>.<br />

These studies were confirmed by Josef Von Mering and Oskar Minkoswki, who<br />

discovered that it was possible to cause <strong>diabetes</strong> in an experimental animal by removing<br />

its pancreas.<br />

Since then all the ef<strong>for</strong>ts of researchers where focused on identifying the pancreatic<br />

extract that was able to cure <strong>diabetes</strong>. In 1921 the Canadians Frederick Grant<br />

Banting and Charles Herbert Best isolated insulin and used it in the famous experiment<br />

involving the dog named arjorie. In 1922, the <strong>young</strong> Leonard Thomson was the<br />

first child <strong>with</strong> <strong>diabetes</strong> in history to be treated <strong>with</strong> insulin. A few years later<br />

insulin was placed commercialized and millions of <strong>people</strong> now owe their lives to it.


What is <strong>diabetes</strong>?<br />

What does having <strong>diabetes</strong> mean?<br />

In order to produce any kind of activity, whether mental or physical, the body<br />

needs energy. This energy is supplied from the cells through the combustion of a first<br />

choice “fuel” named glucose. Glucose is a simple sugar of vital importance, serving as<br />

a source of energy <strong>for</strong> all cells, especially those of the brain and muscles.<br />

At every meal we ingest a number of foods, such as bread, pasta, potatoes and<br />

fruit that contain sugar. During digestion, all of this sugar is converted into glucose,<br />

which is absorbed in the intestine and enters the bloodstream. Glucose needs insulin<br />

to be used by the cells. Like a key, insulin opens the doors of the cells, allowing the<br />

entrance of glucose. Furthermore, through insulin’s action, excess sugar is deposited<br />

in the liver as glycogen, and in adipose cells in the <strong>for</strong>m of triglycerides. Glycogen and<br />

triglycerides represent the fuel reserves to draw from while fasting. They are reconverted<br />

to glucose through the action of glucagon, a hormone which works in an opposite<br />

manner to insulin.<br />

Insulin produced by the pancreas thus regulates the levels of glucose (sugar) in<br />

the blood. In fact, the pancreas of a person who does not have <strong>diabetes</strong> produces insulin<br />

day and night to keep adequate blood glucose. In children and adolescents<br />

<strong>with</strong> <strong>diabetes</strong>, insulin is not produced in a sufficient quantity to meet the body’s<br />

needs and there<strong>for</strong>e the levels of blood glucose rise.<br />

Classification<br />

Different types of <strong>diabetes</strong> mellitus may be develop in children.<br />

Diabetes mellitus Type I<br />

It may affect <strong>people</strong> of any age, but mostly appears in the ages between 0 and<br />

30 years, <strong>with</strong> two peaks of incidence around one to five years of age and 10 and 12<br />

years of age.<br />

In Italy, the annual incidence (number of new cases in a year) differs from region<br />

to region. In England the incidence is 10-12 cases per 100,000 inhabitants/year, while<br />

in Sardinia it is approximately five times as much.<br />

The incidence of childhood <strong>diabetes</strong> seems to be steadily increasing particularly<br />

in children <strong>young</strong>er than 5 years of age.<br />

( 11


What is <strong>diabetes</strong>?<br />

Type 1 <strong>diabetes</strong> mellitus is a disease characterised by the<br />

inability of cells to use glucose – which then accumulates in<br />

the blood – due to the lack of insulin production by the ß-cells<br />

of the pancreas, secondary to their destruction by the immune<br />

system.<br />

12 )<br />

Causes of <strong>diabetes</strong><br />

Type 1 <strong>diabetes</strong> mellitus is caused by the destruction of insulin-producing ß-cells,<br />

which are present in the Islets of Langerhans of the pancreas. This leads to a progressive<br />

decrease in the production of insulin, resulting in increased blood glucose levels.<br />

It is an autoimmune disease. The immune system of <strong>people</strong> <strong>with</strong> type 1 <strong>diabetes</strong>,<br />

which is designed to defend the body from <strong>for</strong>eign agents, such as bacteria and viruses,<br />

is altered, thereby producing antibodies that destroy beta cells. This process is very<br />

slow and may take several years to be completed.<br />

In this period it is possible to look <strong>for</strong> autoantibodies to identify individuals at risk of<br />

developing <strong>diabetes</strong> <strong>with</strong> a simple blood test. Researchers are currently focusing their<br />

interest on these subjects at risk in the hope of identifying a drug or a vaccine that<br />

could stop the autoimmune mechanism and block or delay the development of <strong>diabetes</strong>.<br />

To date, however, only experimental protocols are possible, the effectiveness of<br />

which has yet to be demonstrated.<br />

At the San Raffaele Hospital, you can join one of the largest and most well-known<br />

studies in the world, which is called TrialNet, and which is coordinated by the American<br />

National Institutes of Health. The San Raffaele Hospital is the only Italian centre<br />

admitted to this programme and it is regularly assessed <strong>for</strong> conducting such studies.<br />

It is estimated that the symptoms of the disease arise when around 80% of the<br />

ß-cells have been destroyed. There<strong>for</strong>e at clinical onset there may still be a certain proportion<br />

of cells that produce insulin. For this reason, during the first year of disease<br />

the insulin requirements may be low, and in some cases may remain reduced and suspended<br />

– the so-called “honeymoon” period. However, it is unlikely that this situation<br />

lasts <strong>for</strong> more than a year from onset as all the ß-cells are progressively and irreversibly<br />

destroyed.<br />

Why does the immune system attack the ß-cells? To date there are no known causes<br />

that trigger this destructive mechanism, or its behaviour. What makes the<br />

study of <strong>diabetes</strong> even more troublesome is that the pancreas is a difficult organ to<br />

evaluate because of its anatomical. It is known, however, that there is no single cause:<br />

the disease depends on the interaction between a genetic predisposition and one<br />

or more external (“environmental”) causes.


What is <strong>diabetes</strong>?<br />

Genetic predisposition<br />

Some genes (probably more than 10-15) are responsible <strong>for</strong> increasing the risk<br />

of developing type 1 <strong>diabetes</strong>. However, possessing these genes does not mean that<br />

<strong>diabetes</strong> will surely manifest (as is the case <strong>for</strong> hereditary diseases). The vast majority<br />

of “predisposed” <strong>people</strong> <strong>with</strong> a will never develop <strong>diabetes</strong> because they do not encounter<br />

the environmental “triggering” agent.<br />

For example: in our department about one baby in ten possesses predisposing genes,<br />

but only one in a thousand of these will develop type 1 <strong>diabetes</strong>.<br />

It is known that part of this predisposition is determined by histocompatibility<br />

(HLA) antigens, which are molecules that regulate the immune system. Statistical<br />

analysis has established that <strong>diabetes</strong> is associated mainly <strong>with</strong> HLA DR3, DR4, DQ2 and<br />

DQ8 present in most of the children <strong>with</strong> <strong>diabetes</strong> but also in 20-60% of those <strong>with</strong>out<br />

<strong>diabetes</strong>. Genetic predisposition is supported by the fact that 40% of identical twins<br />

develop <strong>diabetes</strong> and the fact that about 5% of first-degree relatives (parents, siblings<br />

and children) of a person <strong>with</strong> type 1 <strong>diabetes</strong> develop this type of <strong>diabetes</strong>. It is very likely<br />

that there is a certain “dysregulation” of the immune system at the basis of type 1<br />

<strong>diabetes</strong>. This would not allow to limit the destructive process involving ß-cells, which<br />

ultimately determines insulin dependence. It is thought that an initial ß-cell aggression<br />

occurs <strong>with</strong> reasonable frequency, but normally the process is controlled by regulatory<br />

T-cells thereby preventing type 1 <strong>diabetes</strong>. Children <strong>with</strong> <strong>diabetes</strong> have an increased risk<br />

of developing other organ-specific autoimmune diseases such as hypothyroidism and<br />

celiac disease. It is important to emphasise that the immune system of a child <strong>with</strong> <strong>diabetes</strong><br />

is normal and does determine an increased risk of infection.<br />

Environmental factors<br />

It is assumed that one or more environmental triggers may acrivate the immune<br />

response that triggers Type 1 <strong>diabetes</strong> in in a predisposed individuals. Un<strong>for</strong>tunately, to<br />

date there are only hypotheses (infections? diet? other?) and no specific factor has yet<br />

been identified. Finding e trigger is essential as it would allow to create a foundation <strong>for</strong><br />

future prevention. The so-called “environmental” (meaning “non- genetic” in a broad<br />

sense) trigger is definitely very important and responsible <strong>for</strong> the increasing incidence of<br />

<strong>diabetes</strong> that is found nowadays.<br />

Another environmental factor to take into consideration is that the prevalence of<br />

overweight and obese children is rising in several countries including Italy. This probably<br />

does not have a direct effect in the induction of the disease but may highlight earlier<br />

the presence of an ongoing autoimmune ß-cell destruction. It may there<strong>for</strong>e be considered<br />

an anticipatory factor.<br />

Another recently discussed environmental factor involves the gastrointestinal environment,<br />

as many of the immune system’s regulatory cells are generated in the intestine.<br />

The mechanism that correlates the intestinal flora and type 1 <strong>diabetes</strong> is not yet clear,<br />

but this is an area of on-going research.<br />

( 13


What is <strong>diabetes</strong>?<br />

Maturity Onset Diabetes of the Young (MODY)<br />

This is a rare <strong>for</strong>m of <strong>diabetes</strong> that usually manifests in <strong>people</strong> up to 25 years of age.<br />

It is a genetically determined type of <strong>diabetes</strong> (i.e. transmitted in a hereditary manner<br />

from parent to child <strong>with</strong> a very high frequency), and it is there<strong>for</strong>e characterised by<br />

the absence of autoantibodies and not associated <strong>with</strong> obesity. It is caused by a genetic<br />

defect in ß-cell function. In many cases, the diagnosis is carried out by the occasional<br />

identification of hyperglycaemia during routing blood tests. The diagnosis may be confirmed<br />

by genetic testing <strong>for</strong> determined genetic mutations. A number of MODY types<br />

are know: the most common <strong>for</strong>m in Italy is MODY2, which usually does not require<br />

treatment and rarely causes complications. In some cases, however, it may require treatment<br />

<strong>with</strong> oral hypoglycaemic drugs or insulin.<br />

14 )<br />

Neonatal <strong>diabetes</strong><br />

Neonatal <strong>diabetes</strong> is a rare disease which affects about one out of 120,000 babies,<br />

and is characterised hyperglycaemia requiring insulin treatment in the first 6<br />

months of life. It is a disease that may be caused by a wide variety of genetic mutations<br />

that act through different mechanisms. It is not an autoimmune disease such as<br />

type 1 Diabetes.<br />

There are two <strong>for</strong>ms of Neonatal Diabetes: the first and most common is Transient<br />

Neonatal Diabetes Mellitus (TNDM) which develops <strong>with</strong>in the first six weeks of<br />

life and goes into remission <strong>with</strong>in 18 months. In some cases it may recur later in life<br />

(typically during puberty). In more than 80% of cases, TNDM is caused by genetic alterations<br />

involving chromosome 6. Approximately 30% of the remaining cases of TNDM<br />

is instead linked to mutations in the KCNJ11 gene, which also causes Permanent Neonatal<br />

Diabetes (PNDM). The other <strong>for</strong>ms of PNDM identified so far are related to other<br />

mutations: ACCD8, INS, IPF -1, GCK , FOXP3 and EIF2AK3.<br />

The diagnosis of the different <strong>for</strong>ms of neonatal <strong>diabetes</strong> by identifying specific<br />

genetic mutations allows to define specific therapies, in some cases <strong>with</strong> orally taken<br />

hypoglycaemic agents rather than <strong>with</strong> insulin.<br />

Secondary <strong>diabetes</strong><br />

There are other very rare <strong>for</strong>ms of <strong>diabetes</strong> that are considered “secondary” (in the<br />

sense of being “caused by”) to different specific causes: pancreatic, liver, metabolic or<br />

hereditary diseases, or drugs that determine ß-cells damage.<br />

Diabetes Mellitus Type 2<br />

The first reports of cases of Type 2 <strong>diabetes</strong> in children, which appeared in the<br />

1970s, regarded obese adolescents of American Indian origin among Pima Indians in<br />

Arizona. Since the 1990s an increasing incidence of Type 2 <strong>diabetes</strong> has been reported<br />

in the United States, even in adolescents of African-American and Hispanic-American<br />

origins.


What is <strong>diabetes</strong>?<br />

More recently, the phenomenon appeared to also affect the Caucasian population.<br />

In Europe and particularly in Italy, cases of type 2 <strong>diabetes</strong> are not currently numerous<br />

but their frequency is increasing. It is likely that the real extent of the problem<br />

is underestimated because the disease may manifests few symptoms <strong>for</strong> a long period<br />

of time. This <strong>for</strong>m of <strong>diabetes</strong> mostly affects <strong>people</strong> above 40-50 years of age and is<br />

associated <strong>with</strong> overweight. These patients currently represent the majority of the diabetic<br />

population (90 %).<br />

It is not an autoimmune, but it has a significant hereditary component: in fact,<br />

about 90% of identical twins show this <strong>for</strong>m of <strong>diabetes</strong>. A person <strong>with</strong> type 2 <strong>diabetes</strong><br />

produces insufficient quantities of insulin to control blood glucose levels. This is<br />

due to the presence of insulin resistance, which makes insulin ineffective. It is there<strong>for</strong>e<br />

easy to understand why these individuals, unlike those <strong>with</strong> type 1 <strong>diabetes</strong>, may<br />

be treated <strong>with</strong> lifestyle changes (diet and regular exercise), or <strong>with</strong> the use of drugs<br />

that are able to stimulate insulin action and/or secretion (oral hypoglycaemic agents).<br />

In America, Asia and Australia, there have recently been an increasing number of<br />

cases of this type of <strong>diabetes</strong> in children and adolescents. This phenomenon is correlated<br />

to the high frequency of childhood obesity (which involves as much as 40% American<br />

children/adolescents), and ethnic minorities (particularly those of immigrant origins<br />

such as Mexicans, Asians, Indians) because of genetic predisposition.<br />

Risk factors<br />

Obesity. This is the most important risk factor <strong>for</strong> type 2 <strong>diabetes</strong>: more than 85% of<br />

children and adolescents are overweight at disease onset. Obesity may be considered<br />

a worldwide epidemic, especially in children. An important role in the pathogenesis<br />

of the disease is especially attributed to abdominal fat. Obesity in children and adolescents<br />

also causes a reduced sensitivity of peripheral tissues to the action of insulin.<br />

The pancreas tries to overcome this situation by increasing the secretion of insulin<br />

which in some cases may reache high concentrations in the blood (hyperinsulinemia).<br />

This balance may eventually break, resulting in an increase in blood glucose values. In<br />

a minority of cases this condition evolves, already in childhood, into overt <strong>diabetes</strong>.<br />

Genetics. Many genetic factors underlie the susceptibility of the disease by influencing<br />

insulin-resistance. Genetic predisposition is influenced by environmental factors<br />

and lifestyle.<br />

Family history. 45-80% of children <strong>with</strong> Type 2 <strong>diabetes</strong> have at least one parent<br />

<strong>with</strong> <strong>diabetes</strong> and 74-100% have a first and second degree relative <strong>with</strong> Type 2 Diabetes.<br />

Lifestyle. The role of nutrition in the pathogenesis of obesity and type 2 <strong>diabetes</strong> has<br />

been known <strong>for</strong> years, as is the role of a sedentary lifestyle. Physical activity is one of<br />

the factors that may improve glucose tolerance and insulin sensitivity.<br />

Gender and puberty. In the adult population the frequency of <strong>diabetes</strong> mellitus type<br />

2 is slightly higher in females: this phenomenon is much more marked in the paedia-<br />

( 15


What is <strong>diabetes</strong>?<br />

tric population. The risk of developing type 2 <strong>diabetes</strong> is 1.7 times higher in female<br />

adolescents compared to male peers. Diabetes almost always manifests during or after<br />

puberty.<br />

Clinical manifestations<br />

Type 2 <strong>diabetes</strong> may also manifest <strong>with</strong> polyuria, polydipsia, and weight loss. However,<br />

unlike in type 1 <strong>diabetes</strong>, these symptoms are usually modest or absent. In some<br />

cases there may be an acute onset <strong>with</strong> ketoacidosis, although most patients are in<br />

good general conditions. Laboratory tests may show variable levels of blood glucose<br />

and glycosuria <strong>with</strong>out ketonuria.<br />

From now on we will only be discussing type 1 Diabetes, which is the most<br />

common <strong>for</strong>m in children and adolescents.<br />

Diagnostic criteria<br />

Diabetes is diagnosed by measuring the blood glucose levels and the presences of<br />

classic symptoms such as polyuria (frequent urination), polydipsia (constant unquenchable<br />

thirst) and weight loss (due to consumption of fat and muscle mass).<br />

16 )<br />

Classic symptoms of <strong>diabetes</strong> or hyperglycemic crisis, <strong>with</strong> plasma glucose concentration<br />

200 mg/dL,<br />

or<br />

Fasting plasma glucose ≥126 mg/dL. Fasting is defined as no caloric intake <strong>for</strong> at<br />

least 8 h<br />

or<br />

Two hour postload glucose (≥200 mg/dL) during an OGTT


What is <strong>diabetes</strong>?<br />

How it manifests<br />

In type 1 <strong>diabetes</strong>, blood glucose levels progressively increase due to an insufficient<br />

insulin production. This situation determines the onset of a number of evident clinical<br />

manifestations.<br />

The body is equipped <strong>with</strong> a range of alarm systems: one of them is activated when<br />

blood glucose levels exceeds the value of 180 mg/dL, and results in the elimination of<br />

excess glucose in urine.<br />

Since glucose needs a lot of water to be diluted, polyuria i.e. the emission of large<br />

quantities of urine frequently appears as the first symptom. When blood glucose<br />

levels are very high, waking up at night to urinate may become necessary: this<br />

symptom is called nocturia.<br />

Plenty of fluids are lost <strong>with</strong> urine, and there<strong>for</strong>e they must be replaced. This situation<br />

determines what is called polydipsia – intense thirst. As significant amounts<br />

of fluids are lost in urine, there is a progressive dehydration which may present <strong>with</strong><br />

dryness of the skin and mucosal membranes. Moreover, the very “sugary” urine becomes<br />

a great breeding ground <strong>for</strong> bacteria or fungi which may cause urinary tract infections<br />

and vaginal discharge.<br />

Weight loss. Although there are high levels of glucose in the blood, it cannot be<br />

used to the lack of insulin. The body’s cells there<strong>for</strong>e exploit second choice energy<br />

sources such as stored fat and muscle proteins. In addition to losing weight, the body<br />

responds <strong>with</strong> an intense hunger called polyphagia to try to replenish the body<br />

<strong>with</strong> energy. Due to this metabolic derangement, also intense fatigue may progressively<br />

develop.<br />

Fats used as “second choice” fuel also produce waste such as ketones, which are<br />

eliminated in urine (ketonuria or acetonuria) and in exhaled air (acetone smelling breath<br />

<strong>with</strong> the characteristic odour of rotten fruit). If this process is not interrupted,<br />

the blodd’s acidity progressively drops eventually causing ketoacidosis, a serious<br />

acute situation that requires emergency hospitalization.<br />

( 17


What is <strong>diabetes</strong>?<br />

Therapy<br />

When type 1 <strong>diabetes</strong> is diagnosed, the patient should be hospitalized in a paediatric<br />

ward in which there is a team (doctors, nurses, dietitians, psychologists - educators)<br />

specifically qualified to take care of children <strong>with</strong> <strong>diabetes</strong>. This group of specialists also<br />

monitors the child in outpatient check-ups.<br />

The treatment of <strong>diabetes</strong> does not end <strong>with</strong> the hospitalization of the patient<br />

but must be continued in in everyday life. The child and his/her family are there<strong>for</strong>e<br />

key players in the management of <strong>diabetes</strong>.<br />

Diabetes care is based on four cornerstones:<br />

self-control education<br />

insulin “replacement” therapy<br />

adequate nutrition<br />

regular physical activity<br />

The aim is to try to achieve the full psychological and physical well-being of the<br />

child and effective prevention of <strong>diabetes</strong> complications secondary to and adequate<br />

metabolic control.<br />

Prevention means avoiding the onset or slowing the progression of macrovascular<br />

and microvascular complications that could lead to a deterioration in the quality of<br />

life of a person suffering from <strong>diabetes</strong>.<br />

In other words, implementing prevention means avoiding damage to the eye’s<br />

retina, kidney, nervous system and circulation at especially <strong>for</strong> what concerns the heart<br />

and lower limbs. To implement an effective prevention strategy, all the therapeutic<br />

options in our possession should be used: insulin therapy, which has changed the natural<br />

history of insulin-dependent patients, remains the fundamental therapeutic tool.<br />

18 )<br />

It is important <strong>for</strong> a child <strong>with</strong> <strong>diabetes</strong> and his/her family to<br />

learn how to manage themselves correctly in all the situations<br />

that life may present.


Self-monitoring<br />

of blood glucose


Self-monitoring of blood glucose<br />

Doctors and other specialists are experts that provide the instructions, but it is the family<br />

that has to adapt the in<strong>for</strong>mation to the needs of everyday life. Diabetes self-management<br />

may carried out by using specific tools, mainly blood glucose and ketone<br />

measurements, which allow to quickly identify glucose oscillations. Frequent testing,<br />

defined as “self-monitoring”, allows a child/<strong>young</strong> adult <strong>with</strong> <strong>diabetes</strong>, who is properly<br />

instructed by a health care team, to manage his/her own insulin therapy.<br />

It is important to note that only by carrying out these allows us to understand<br />

how blood glucose levels vary throughout the day. This means taking about 5 to 7 blood<br />

glucose values per day.<br />

It is absolutely impossible to rely on symptoms to determine your blood<br />

sugar level.<br />

A person who does not have <strong>diabetes</strong> has blood glucose levels that roughly vary<br />

between 65 and 126 mg/dL throughout the day.<br />

A <strong>young</strong>ster <strong>with</strong> <strong>diabetes</strong> should have the following reference values<br />

(reference values may be individually determined <strong>with</strong> a specialist):<br />

between 80 and 120 mg/dL when fasting<br />

between 90 and 180 mg/dL after meals<br />

between 120 and 180 mg/dL be<strong>for</strong>e bedtime<br />

Hyperglycaemia there<strong>for</strong>e means having a value greater than 120 mg/dL when<br />

fasting and 180 mg/dL after meals. These are reference values which children/adolescents<br />

<strong>with</strong> <strong>diabetes</strong> should aim <strong>for</strong>. It is impossible <strong>for</strong> a child <strong>with</strong> <strong>diabetes</strong> to<br />

never have hyper- or hypoglycaemia. Blood glucose oscillations should not raise<br />

concerns if they remain occasional. In preschool children (who are particularly sensitive<br />

to insulin) it may be necessary to increase the blood glucose reference ranges reduce<br />

the risk of hypoglycaemia.<br />

20 )<br />

Where to per<strong>for</strong>m blood glucose measurements<br />

Fingers are a particularly adequate site <strong>for</strong> blood glucose testing as they a richly vascularized.<br />

Small pricks can be per<strong>for</strong>med, generating a small amount of blood which<br />

is sufficient <strong>for</strong> testing.<br />

Each finger may be pricked on the tip or on the side. It is important to use all<br />

the fingers in rotation to avoid the hardening of the skin and a reduction in sensitivity.<br />

Newer blood glucose meters use smaller blood samples (0.2-0.5 microlitres) and allow<br />

testing on alternative sites (palm of your hands and <strong>for</strong>earms). By using the <strong>for</strong>earm<br />

blood glucose variations may be observed <strong>with</strong> a delay of 15 minutes compared<br />

to the fingertip/hand. There<strong>for</strong>e, alternative sites such as the <strong>for</strong>earm should be used<br />

only <strong>for</strong> fasting blood glucose determinations.


Self-monitoring of blood glucose<br />

How the test<br />

The measurement of blood glucose at home is per<strong>for</strong>med by taking a drop of blood<br />

from a small prick on the fingertips <strong>with</strong> a special calibrated lancing device, which makes<br />

it almost painless.<br />

If the temperature is low, warm your hands to increase the flow of blood. Generally,<br />

it is not necessary to disinfect where you prick the skin (washing hands <strong>with</strong> soap<br />

and water may be enough), but if you do make sure the finger is completely dry be<strong>for</strong>e<br />

proceeding. For hand washing we recommend using warm water: warm hands<br />

allow a better flow of blood.<br />

Place the drop of blood in contact <strong>with</strong> the test strip inserted in the instrument, and<br />

in a few seconds a blood glucose value will appear on the display.<br />

The devices are equipped <strong>with</strong> memory that can record the results obtained in previous<br />

weeks and allow you to check your average blood glucose level.<br />

It is also possible to connect the instrument to a personal computer, thereby obtaining<br />

statistics and graphs regarding your blood glucose values that are useful in the<br />

evaluation of glucose oscillations in specific tiems of the day. These data may be<br />

sent and/or discussed <strong>with</strong> your <strong>diabetes</strong> specialist.<br />

Each instrument has its own specific calibration: there<strong>for</strong>e it is neither recommended<br />

to frequently change the one you use, nor to compare the results obtained <strong>with</strong><br />

two different instruments.<br />

Each meter has a margin of error of about 10-15%: there<strong>for</strong>e, by repeating the test<br />

multiple times <strong>with</strong>in a few minutes you may get slightly different results (the higher<br />

the blood glucose value, the higher the difference) but which are still representative<br />

of the same blood glucose value at that moment.<br />

The meter must not be exposed to extremely high or low temperatures.<br />

Some older meters require verification of the code that appears on the strips that<br />

are used <strong>for</strong> dosage. A mismatch between the instrument’s code and the strips may<br />

lead to significant errors. Newer instruments do not require coding (“no-code” instruments).<br />

Certain substances may interfere <strong>with</strong> the per<strong>for</strong>mance of the test, such as certain<br />

medications (ie. Acetamol).<br />

( 21<br />

Possible errors when per<strong>for</strong>ming the test:<br />

it is necessary to dry your finger be<strong>for</strong>e pricking it, otherwise blood will be diluted,<br />

and the blood glucose value will be altered.<br />

be careful to temperature:<br />

> If it is less than 10°C, the measured values are lower than the actual values<br />

> If it is above 35°C, the measured values are higher than the actual values


Self-monitoring of blood glucose<br />

When you per<strong>for</strong>m the test<br />

The purpose of blood glucose monitoring is to determine whether or not insulin doses<br />

are adequate. In particular, it is important to know that:<br />

after meals (ie. breakfast, lunch and dinner) the blood glucose value depends on rapid-acting<br />

insulin administered be<strong>for</strong>e the meals;<br />

fasting blood glucose values (upon awakening, be<strong>for</strong>e meals, and at night) mainly<br />

depend on the long-acting insulin administered in the morning or at bedtime.<br />

How often to test your blood glucose<br />

The blood glucose test must be per<strong>for</strong>med at different times of the day in order to<br />

obtain in<strong>for</strong>mation in all time frames. In particular, we recommend and average of 5-7<br />

blood glucose measurements a day.<br />

You should measure your blood glucose levels often to adjust insulin doses according<br />

to your own needs, to assess the effect different activities and meals, and above<br />

all to have all the in<strong>for</strong>mation you need to independently and safely change insulin<br />

doses.<br />

Patients who use insulin pumps usually check their blood sugar more frequently<br />

(8-10 times a day) to prevent possible hypoglycaemia and promptly and accurately<br />

adjust the dose of insulin (fine-tuning).<br />

Urine Dipstick Tests<br />

22 )<br />

Urine dipstick tests complement the in<strong>for</strong>mation provided by glucose measurements.<br />

Per<strong>for</strong>ming these tests is simple: dip the strips in urine, and the reactive squares will<br />

start progressively change color in a few seconds. You may obtain the result by comparing<br />

the colors on the strip <strong>with</strong> the reference table on the strip container.<br />

Glycosuria<br />

If your blood glucose is less than 160-180 mg/dL (renal threshold value) glucose will<br />

not be appear in urine. There<strong>for</strong>e, a non-diabetic whose blood glucose rarely exceeds<br />

120 mg/dL, will never have sugar in his/her urine.<br />

However, if the blood glucose level exceeds this threshold, glucose will pass into the<br />

urine. The higher the blood glucose value the more glucose in urine there will be.<br />

This is why the amount of sugar in urine, also called glycosuria, may indirectly<br />

provide in<strong>for</strong>mation on blood glucose levels. For example, if in the morning when you<br />

wake up the test shows a urine glucose level of 5 g/l, this means that during the night<br />

the blood sugar level was greater than 180 mg/dL, there<strong>for</strong>e providing an important<br />

in<strong>for</strong>mation that would have otherwise been overlooked. Unlike blood glucose mea-


Self-monitoring of blood glucose<br />

surements, glycosuria provides in<strong>for</strong>mation that relates to a time interval; it does not<br />

detect the blood sugar level at the time, but its trend since the last time the bladder<br />

was emptied.<br />

Currently, the determination of glycosuria is of minor importance <strong>for</strong> those who<br />

regularly and frequently per<strong>for</strong>m blood glucose tests.<br />

Sugar<br />

Blood<br />

Glycaemia<br />

180<br />

mg/dl<br />

Urine<br />

Urinary ketones<br />

It is also possible to determine acetone or ketones (ketonuria or acetonuria) in urine.<br />

Ketones are produced by the liver when fats and proteins are used to produce<br />

energy. If it is not possible to use glucose, the body will then rely on fat<br />

to produce energy. However, this also determines the production of waste material<br />

such ketones. Beyond a certain value, ketones accumulate in the blood and are then<br />

subsequently eliminated in urine and exhaled air.<br />

There<strong>for</strong>e, when ketones appear in urine, it means that the cells were not able<br />

to use glucose but drew energy from fat. This may happen in two distinct situations:<br />

During prolonged hypoglycaemia, in other words when there is short supply of first<br />

choice fuel (glucose).<br />

In case of lack of insulin (and there<strong>for</strong>e hyperglycaemia), which prevents glucose<br />

from entering the cells. This may occur <strong>diabetes</strong> onset or <strong>with</strong> poorly controlled <strong>diabetes</strong>.<br />

These two situations can easily be distinguished by measuring blood glucose. The<br />

urine ketone test is of fundamental importance during in case of prolonged hyperglycaemia<br />

and during intermittent illnesses (ie. flu). A person <strong>with</strong> <strong>diabetes</strong> must<br />

never have ketones in his/her urine.<br />

( 23<br />

Interpretation of the tests<br />

A person <strong>with</strong> <strong>diabetes</strong> <strong>with</strong> good metabolic control will always have negative urine<br />

tests. The examples below refer, <strong>for</strong> purposes of convenience, to morning urine.


Self-monitoring of blood glucose<br />

If neither glucose or ketones are found in morning urine<br />

this means that blood glucose was less than 180 mg/dL during the night; the possibility<br />

of hypoglycaemia cannot be excluded; a blood sugar level test in the night<br />

is necessary to check this.<br />

Glycosuria<br />

Acetonuria<br />

If only glucose is found in morning urine<br />

this result tells us that blood glucose exceeded the threshold of 180 mg/dL during<br />

the night. To determine the precise time and level it is necessary to check your blood<br />

sugar level several times during the night.<br />

If only ketones are found in morning urine<br />

hypoglycaemia probably occurred at night. Glucose is not present in urine as the<br />

180 mg/dL threshold has not been surpassed, however fat tissue had to be used there<strong>for</strong>e<br />

producing energy and ketones.<br />

24 )<br />

If both glucose and ketones are found in morning urine<br />

the blood sugar level exceeded 180 mg/dL at night and fats were also used <strong>for</strong> energy.<br />

There are two possibilities:<br />

hypoglycaemia occurred followed by a significant rise in blood glucose, caused<br />

by the activation of counter regulatory mechanisms (hormones that release sugar<br />

stored in the liver). This phenomenon is called “rebound effect” and is the most<br />

likely hypothesis if it appears to be an isolated event and does not follow a period<br />

of poor control. To verify this hypothesis it is necessary to measure nigh-time blood<br />

glucose to prove the presence of nocturnal hypoglycaemia;<br />

there was a prolonged episode of hyperglycaemia caused by an insufficient dose<br />

of insulin. It is there<strong>for</strong>e necessary to measure your blood sugar immediately because<br />

this may be warning sign that the body is in a state of poor metabolic equilibrium<br />

and needs more insulin. Rapid-acting insulin must be administered and blood glucose<br />

must be checked every 2-3 hours. If blood glucose does not normalize <strong>with</strong>in<br />

6 hours, it is better to contact your doctor immediately or go to the emergency department.<br />

This situation may also occur during acute illnesses.<br />

Capillary blood ketones<br />

Some devices, by using ketone-specific strips, can measure ketone concentrations<br />

from a drop of capillary blood, in the same way blood glucose is measured. In this<br />

way it is also possible to monitor blood ketone – which is very useful in case of poor<br />

metabolic control. With these meters, accurate measurements (values > 0.6 mmol/l<br />

are considered positive) allow to observe a rise in ketones long be<strong>for</strong>e the their presence<br />

in urine.


Self-monitoring of blood glucose<br />

Blood ketone measurement are very important <strong>for</strong> the following patients:<br />

newborns or toddlers who use a diaper, making it difficult to test <strong>for</strong> ketones in urine;<br />

during infectious diseases;<br />

in all cases where diabetic ketoacidosis needs to be prevented;<br />

patients using insulin pumps,<br />

Monitoring <strong>for</strong> the presence of ketone must be carried out immediately in the presence<br />

of persistently elevated blood glucose and during any type of intercurrent illness<br />

(fever, diarrhoea, vomiting). The presence of ketone is an alarm signal that requires<br />

immediate action.<br />

The Glucose Diary<br />

Keeping a glucose diary <strong>with</strong> blood glucose values helps the self-management <strong>diabetes</strong><br />

and helps caregivers evaluated glucose control more effectively. It is important record<br />

the following data in the diary: any change in weight, intercurrent illness (fever,<br />

infections, colds, etc.), menses, and physical activities. Statistical assessment of glucose<br />

values (e.g. monthly averages and variability indices) can be obtained using computers.<br />

Spreadsheets may can also be used record blood sugar levels.<br />

Pre-school children (under 6 years of age) require a lot of blood glucose level<br />

tests (up to 12 per day) because of the extensive variability in nutrition and physical<br />

activity and because they are not able to identify the symptoms of hypoglycaemia on<br />

their own.<br />

Day<br />

morning<br />

BG<br />

insulin<br />

BG after<br />

breakfast<br />

BG be<strong>for</strong>e<br />

lunch<br />

insulin<br />

BG after<br />

lunch<br />

BG be<strong>for</strong>e<br />

snack<br />

insulin<br />

BG be<strong>for</strong>e<br />

dinner<br />

insulin<br />

BG after<br />

dinner<br />

insulin<br />

bedtime<br />

BG<br />

nighttime<br />

BG<br />

( 25<br />

1<br />

2<br />

3<br />

4<br />

Morning<br />

Lunch<br />

Snack<br />

Dinner<br />

Night<br />

5<br />

6<br />

7


Insulin therapy


Insulin therapy<br />

What is insulin?<br />

Insulin is a hormone produced by ß-cells harvested in the Islets of Langerhans in the<br />

pancreas: its main function is to maintain normal blood glucose levels.<br />

The pancreas is an organ located deep in the abdomen which per<strong>for</strong>ms two important<br />

functions:<br />

Exocrine: through the release of pancreatic enzymes, it allows the digestion of food<br />

(fat, sugar, protein) in the intestine<br />

Endocrine: through the release of hormones such as insulin, glucagon, and somatostatin<br />

into the bloodstream, which are essential <strong>for</strong> proper glucose metabolism.<br />

Except <strong>for</strong> the secretion of insulin, endocrine and exocrine functions are substantially<br />

normal in diabetics.<br />

The release of insulin from the pancreas is regulated by blood glucose levels: the<br />

pancreas of a person <strong>with</strong>out <strong>diabetes</strong> secretes a small amount of insulin in a continuous<br />

manner, allowing the body to use blood glucose in order to produce energy<br />

<strong>for</strong> the body’s needs. This is called the basal insulin requirement. However, the insulin<br />

requirement and there<strong>for</strong>e its concentration in the blood does not remain constant<br />

during they day due to many influencing factors such as physical activity or an<br />

intercurrent illness.<br />

After having consumed a meal or beverage containing carbohydrates,<br />

blood glucose increases. In <strong>people</strong> <strong>with</strong>out <strong>diabetes</strong>, the pancreas “automatically”<br />

detects a rise in blood sugar and secretes adequate amounts of insulin in a short time<br />

to prevent blood glucose from exceeding the normal levels.<br />

If the pancreas is unable to do this, blood glucose is not used by the body’s cells<br />

and there<strong>for</strong>e it increases (except in brain and muscle cells, in which sugar can enter<br />

regardless of insulin action).<br />

( 27


Insulin therapy<br />

Insulin therapy<br />

Type 1 Diabetes is treated via a “substitution” process: the insulin that the pancreas<br />

no longer produces is provided by an external administration. Many advances have<br />

been made since the discovery of insulin in 1922: it was initially, extracted from the<br />

pancreas of animals and then synthetically produced in laboratories. Human insulin<br />

obtained <strong>with</strong> molecular biology has been available <strong>for</strong> many years.<br />

Insulin is measured in units (abbreviation U) which can be dosed <strong>with</strong> a syringe,<br />

pen or insulin pump; in Italy the concentration is always 100 U/ml.<br />

The main purpose of the administration of insulin is, of course, to achieve the<br />

best possible glycaemic control throughout the day. Several studies have shown that<br />

insulin treatment <strong>with</strong> multiple injections (>4 per day) allows a better glycaemic homeostasis.<br />

By increasing the number of doses, the insulin secretion in the pancreas of<br />

a non-diabetic person is mimicked.<br />

There are currently various insulin <strong>for</strong>mulations <strong>with</strong> different durations of action:<br />

regular or rapid-acting, rapid-acting insulin analogs, intermediate-acting insulin,<br />

long-acting insulin analogs, and premixed insulins.<br />

The possibility to use different types of insulin makes it easier to achieve optimal<br />

glycaemic control. Rapid-acting insulin are used be<strong>for</strong>e meals and long-acting insulins<br />

are used to cover the 24 h basal insulin requirement.<br />

28 )<br />

However, obtaining an adequate glycaemic profile is not always simple.<br />

Numerous factors related to the mode of administration, absorption and action of<br />

counter-regulatory hormones, such as growth hormone which has a hyperglycaemic<br />

action, may make it difficult to achieve glucose control.<br />

In <strong>young</strong>er children it is also difficult to plan physical activity (often sudden,<br />

intense and unpredictable). During adolescence, a period characterised by the desire<br />

<strong>for</strong> freedom from constraints), the commitment to self-control is sometimes lacking.


Insulin therapy<br />

Rapid-acting insulin<br />

This insulin is identical in structure to human insulin. It has a clear and transparent appearance<br />

and is also called “regular” insulin. It is used to cover postprandial needs. It is<br />

rarely prescribed in current practice, because rapid-acting insulin analogs are preferred.<br />

Mode of action:<br />

onset of action: 30 minutes after an injection<br />

peak action: after 2-3 hours<br />

total duration of action: 5-6 hours<br />

2h<br />

6h<br />

0 2 4 6 8 10 12<br />

p<br />

Example: insulin administered at 7 a.m. in the<br />

morning starts to act at 7:30 a.m., has its maximum effectat 9 to 10 a.m., and<br />

its effect ends at about 12 to 1 p.m.<br />

Monitoring blood glucose: 2 hours after a meal<br />

Administration method:<br />

if your blood sugar is in the normal range you have to start eating your<br />

meal 30 minutes after an injection<br />

in the event of hypoglycaemia (values less than 60 mg/dL) we recommend<br />

correcting the hypoglycaemia and taking the injection 15 minutes be<strong>for</strong>e<br />

meals<br />

when blood glucose is above 300 mg/dL, you can anticipate the<br />

administration by 40-45 minutes be<strong>for</strong>e the meal<br />

Fast-acting insulin analog<br />

This insulin, also called ultra-rapid insulin, is obtained by modifying the structure of<br />

human insulin in order to obtain a higher absorption rate than traditional rapid-acting<br />

insulin, <strong>with</strong> a mechanism of action that is closer to the postprandial insulin production<br />

of non-diabetics.<br />

It is an aqueous, sterile, clear and colourless solution. Formulations are available <strong>for</strong><br />

syringe and pen administration.<br />

( 29<br />

Mode of action:<br />

onset of action: 10-20 minutes after the injection<br />

peak action: after 1-3 hours<br />

total duration: 3-5 hours<br />

1h<br />

3h<br />

0 2 4 6 8 10 12


Insulin therapy<br />

EXAMPLE: ultrafast insulin injected at 1 p.m. starts to act at 1.10 p.m., has its<br />

maximum effectiveness at 2 p.m. and its effect ends at about 4 – 6 p.m.<br />

The duration depends on the total dose. In <strong>people</strong> who take more than 0.3<br />

units/kg of weight (<strong>for</strong> example, weighing 40 kg and take more than 12 units)<br />

the effect of ultrafast insulin can last up to six hours after the injection.<br />

Monitoring of blood glucose: 1-2 hours after a meal<br />

Administration method:<br />

if your blood sugar is in the normal range you should wait 10-15 minutes<br />

after an injection to start eating<br />

in the presence of hypoglycaemia we recommend to first correct the<br />

low blood sugar as shown in the diagram. After the blood glucose has<br />

returned in the normal range, administer the dose of insulin right be<strong>for</strong>e<br />

consuming the meal.<br />

in case of hyperglycaemia a correction dose is added to the meal dose<br />

30 )<br />

By using a rapid-acting insulin analog, the time between injection and meal is reduced.<br />

You do not have to wait 30 minutes between an injection and a meal like traditional<br />

insulin as 15 minutes may suffice.<br />

In some situations it is not possible to predict the patient’s eating habits (because<br />

he/she has a variable appetite or because of illnesses that result in the loss of appetite,<br />

nausea or vomiting). In these cases it is possible to administer ultrafast insulin after<br />

meals, so that the injected dose is adequate in proportion to the amount of consumed<br />

carbohydrates. Ultrafast insulin must always be used <strong>for</strong> the administration of<br />

an extra- dose in the presence of occasional hyperglycaemia or snacks eaten between<br />

meals. The absorption rapidity reduces postprandial hyperglycaemia.<br />

As a result of the shorter duration of action, ultrafast insulin also reduces the risk<br />

of delayed hypoglycaemia. For these reasons it allows the elimination of “mandatory”<br />

snacks between meals. Ultrafast insulin must always be used alongside a daily dose<br />

of long-acting insulin.<br />

Intermediate-acting insulin<br />

Because of the presence of protamine (NPH), this insulin has a slower absorption from<br />

the injection area. It has a milky appearance.<br />

Mode of action:<br />

onset of action: 1-2 hours after an injection<br />

peak action: after 5-6 hours<br />

total duration:10-12 hours<br />

5h<br />

12h<br />

0 2 4 6 8 10 12


Insulin therapy<br />

EXAMPLE: intermediate-acting insulin administered at 7a.m. starts working<br />

at 8 – 9 a.m. , has its maximum effectiveness at 1 p.m. to 3 p.m. and its effect<br />

ends around 7 p.m.<br />

Monitoring of blood glucose levels: while fasting, be<strong>for</strong>e meals<br />

Administration method<br />

Since the function of this type of insulin is to maintain the blood glucose level between<br />

meals through a slow and continuous release into the bloodstream, it is generally<br />

administered twice a day: in the morning in association <strong>with</strong> a rapid-acting insulin<br />

and in the evening be<strong>for</strong>e dinner or be<strong>for</strong>e bedtime. Being a suspension liquid it is necessary<br />

to shake it delicately by turning it upside down at least 10 times be<strong>for</strong>e use.<br />

Premixed insulin<br />

This is a type of insulin containing both ultrafast and intermediate-acting insulin<br />

(NPH). The proportion of rapid-acting and intermediate insulin varies depending on<br />

the type of premixed insulin; you can find the following proportions on the market:<br />

25/75, 30/70, 50/50, 70/30. The first number represents the percentage of rapid acting<br />

insulin and the second the percentage of intermediate-acting insulin.<br />

The use of pre-mixed insulins in children is strictly dependent on the stability of<br />

the blood glucose values as it is impossible to change only the rapid-acting proportion<br />

<strong>with</strong>out affecting the intermediate dose. It is there<strong>for</strong>e a less “flexible” kind of insulin<br />

to use in children especially in case of unpredictable eating habits and physical activity.<br />

Mode of action:<br />

onset of action: 30 minutes after an injection<br />

peak action: after 2-3 hours<br />

total duration: 10-12 hours<br />

2h<br />

10h<br />

( 31<br />

0 2 4 6 8 10 12<br />

EXAMPLE: premixed insulin administered at 7<br />

a.m. in the morning starts to work at 7:30 a.m.,<br />

has its maximum effect at 9 to 10 a.m. and its effect ends at around 5 to 7<br />

p.m.<br />

Monitoring blood glucose levels: 2 hours after a meal and be<strong>for</strong>e the next meal<br />

Administration method: see those <strong>for</strong> the administration of rapid-acting insulin


Insulin therapy<br />

Long-acting insulin analogs<br />

Long-acting insulin analogs ensure ‘baseline’ insulinization – the minimum insulin required<br />

between meals and rest. There are two types of similar long-acting insulins<br />

which are obtained by modifying the insulin molecule in order to obtain a slow absorption<br />

and there<strong>for</strong>e a long mechanism of action.<br />

Lantus (glargine). Lantus is an insulin whose effectiveness is maintained, in most<br />

cases, <strong>for</strong> 20-24 hours.<br />

Mode of action:<br />

onset of action: 2 hours after an<br />

injection<br />

peak action: it has no peaks, its action<br />

is homogenous<br />

total duration: 18-20 hours<br />

h<br />

0 2 4 6 8 10 12 14 16 18 20 22 24<br />

EXAMPLE: if you inject it at 10 p.m. it will begin to work at midnight and last<br />

until 10 p.m. the next day.<br />

It is preferable to inject Lantus in the buttocks where the absorption is slower.<br />

Levemir (Detemir). Levemir is another long-acting insulin <strong>with</strong> a different mechanism<br />

of action compared to Lantus. This is also a transparent insulin and binds to circulating<br />

albumin once it has entered the bloodstream. It is then slowly released in order<br />

to obtain a prolonged effect.<br />

32 )<br />

Mode of action:<br />

onset of action: 2 hours from injection<br />

peak action: while a dose of 0.2/0.3<br />

U/kg does not have a peak, a higher<br />

dose determines a peak after about<br />

6-9 hours.<br />

total duration: 12-16 hours<br />

h<br />

0 2 4 6 8 10 12 14 16 18 20 22 24<br />

Levemir is normally injected twice a day.


Insulin therapy<br />

How to store insulin<br />

To address this issue it is necessary to distinguish between insulin currently in use and<br />

unused insulin.<br />

Unused insulin should be stored in a refrigerator at a temperature between +2°C<br />

and +8°C.<br />

Insulin vials or pens which are being used are to be kept at room temperature<br />

(below 25°C) <strong>for</strong> a maximum period of one month. It must not be frozen, or exposed<br />

to excessive heat or direct sunlight. It may also be stored in the fridge – remember to<br />

bring it to room temperature at least 20 minutes prior to administration since refrigerated<br />

insulin may cause pain in the injection site. Insulin that is currently in use and<br />

stored in a refrigerator should be discarded 2 months after it’s first use.<br />

It is advisable to mark the date of first use in order to calculate the expiration date.<br />

Insulin therapy schedule<br />

By using different types of insulins it is possible to develop a daily administration schedule<br />

or ‘tailor-made’ insulin administration schedule <strong>for</strong> each child <strong>with</strong> <strong>diabetes</strong>, according<br />

to their individual needs. Different daily habits and individual insulin sensitivity<br />

make it impossible to determine standard insulin doses that are common to everyone.<br />

However, there has now been an acceptance of the theory that a greater number<br />

of boluses gives better control of blood sugar levels and there<strong>for</strong>e a lower risk of<br />

complications. However, we must not <strong>for</strong>get that only the patient’s cooperation and<br />

education in self-management, appropriate dietary education and regular physical activity,<br />

aid in achieving optimal control.<br />

The guiding principle of modern insulin therapy is to try to develop an insulin administration<br />

that mimics as much as possible that of physiological pancreas <strong>with</strong> working<br />

ß-cells. A normal pancreas continuously secretes a small amount of insulin (basal<br />

insulin) and then precisely increases/decreases insulin administration according to<br />

increasing (<strong>for</strong> example during a meal) or decreasing (<strong>for</strong> example during physical activity)<br />

blood glucose.<br />

This is the concept by which basal/bolus insulin regimens are considered the main<br />

mode of insulin replacement therapy.<br />

An overall daily dose of insulin of up to 1-1.3 units per kilogram of body weight<br />

is normal, especially during adolescence.<br />

When choosing a therapeutic regimen, one must take into account the habits<br />

and meal times of the child and his/her family: insulin use must be adapted to the<br />

needs of the person <strong>with</strong> <strong>diabetes</strong> and not vice versa.<br />

There are several possible regimens <strong>with</strong> at least 3 insulin injections per day.<br />

Schedules that are now considered effective involve the administration of rapid insu-<br />

( 33


Insulin therapy<br />

lin analogs be<strong>for</strong>e meals and snacks and long acting insulin analogs in a single dose<br />

(usually at bedtime) or two doses at bedtime and in the morning. The use of premixed<br />

insulin is limited, particularly in children.<br />

Due to the scarsity of data present in literature regarding the use of long acting<br />

insulin analgos in children under 2 years of age, it’s prescription in this age group is<br />

very limited. There<strong>for</strong>e, a schedule <strong>with</strong> intermediate acting insulin (NPH) and rapid<br />

acting insulin analogs is usually proposed. Intermediate acting insulin and rapid acting<br />

analogs may be mixed, allowing <strong>for</strong> a reduction in the number of injections. This schedule<br />

is an alternative to the use of an insulin pump, which is probably the best therapeutic<br />

option in this age group.<br />

Examples of insulin regimens<br />

The insulin regimen that is by far the most used in patients of all ages is the so-called<br />

basal-bolus regimen. It consists of an injection of rapid-acting insulin analog be<strong>for</strong>e<br />

each meal and and usually on injection of log acting insulin analog (usually glargine)<br />

at bedtime.<br />

Basal bolus regimen<br />

chedule<br />

Be<strong>for</strong>e breakfast: rapid acting insulin analog<br />

Be<strong>for</strong>e lunch: rapid acting insulin analog<br />

Be<strong>for</strong>e dinner: rapid acting insulin analog<br />

Be<strong>for</strong>e going to sleep: long acting insulin analog<br />

Another common regimen involves two injections of rapid acting insulin analog<br />

alone be<strong>for</strong>e breakfast and dinner, an injection of rapid acting insulin analog mixed<br />

<strong>with</strong> NPH be<strong>for</strong>e lunch, and NPH insulin at bedtime.<br />

chedule<br />

34 )<br />

Schedule<br />

Be<strong>for</strong>e breakfast: rapid acting insulin analog<br />

Be<strong>for</strong>e lunch: rapid acting insulin analog + NPH<br />

Be<strong>for</strong>e dinner: rapid acting insulin analog<br />

Be<strong>for</strong>e going to bed: NPH<br />

The latter regimen is may be an alternative <strong>for</strong> <strong>young</strong> children of up to 6 years of<br />

age as the bedtime NPH profile may better satisfy the insulin requirements of a preschool<br />

child.<br />

Type 1 <strong>diabetes</strong> may be considered well-controlled when the blood sugar level<br />

values are optimal (HbA1C < 7.5% or 52 mmol/mol) regardless of the type of schedule,<br />

the number of injections or the daily insulin requirement.


Insulin therapy<br />

General principles <strong>for</strong> changing doses<br />

How and when to change an insulin dose depends on the type of insulin regimen, however<br />

there are certain ‘golden rules’ that on has to keep in mind.<br />

After meals, blood sugar values mainly depend on rapid-acting insulin, while fasting<br />

blood sugar levels usually depend on the activity of delayed insulin.<br />

In the presence of a single high blood glucose value (hyperglycaemia) it is wise to<br />

check your blood glucose level in the following days in a that same time-frame, in order<br />

to see whether or not it is a sporadic event.<br />

If blood glucose is still high <strong>for</strong> 2 or 3 consecutive days in the same time frame,<br />

and no specific causes may be identified (ie. diet and/or exercise), it is necessary to<br />

increase the dose of insulin acting at that time by 10% (usually 0.5-1 U). In the following<br />

days you should check your blood glucose in the same time period to evaluate<br />

the adequacy of the insulin dose modification. If blood glucose is still elevated, one<br />

can repeat the 10% increase.<br />

If an unexplained hypoglycaemia occurs, the dose of insulin acting in that timeframe<br />

should be reduced by 10% (0.5-1 U) the following day.<br />

There are many factors that affect blood glucose levels (diet, exercise, illnesses,<br />

menstrual cycle, etc), and insulin is only one of them. Thus, be<strong>for</strong>e deciding on changing<br />

your insulin dose it is always important to ask yourself the following questions:<br />

At what time is your blood glucose too high or too low?<br />

Are there any identifiable reasons (exercise, diet, illness or other)?<br />

Which type of insulin is acting in that time period?<br />

How much do you need to increase the dose?<br />

Insulin-to-carbohydrate (IC) ratio<br />

The IC ratio expressesas the amount of carbohydrates (in grams) that is metabolized<br />

by one unit of rapid acting insulin. For example, a ratio of 1/15 means that 15 g of<br />

carbohydrates are metabolized by 1 unit of insulin.<br />

( 35<br />

EXAMPLE: A person <strong>with</strong> a IC ratio of 15 decides to eat 75 grams of<br />

carbohydrates. 75:15 = 5. He/she must there<strong>for</strong>e plan a preprandial bolus of<br />

5 units.<br />

The IC ratio is generally calculated by dieticians on the basis of a careful analysis<br />

of the dietary records kept by the person <strong>with</strong> <strong>diabetes</strong>. The latter should, at least <strong>for</strong><br />

a few weeks, record the blood sugar level be<strong>for</strong>e each meal or snack or drink containing<br />

carbohydrates, as well as the blood glucose level afterwards and the carbohydrate<br />

content of the meal (or weight or type of food <strong>with</strong> the ingredients).<br />

The IC ratio may vary considerably during the day. For example, those who exer-


Insulin therapy<br />

cise in the afternoon and have a sedentary morning find that their insulin ‘works better’<br />

- and there<strong>for</strong>e ‘burns’ more carbohydrates - at dinner rather than at lunch. The<br />

same is true in the summer compared to winter.<br />

36 )<br />

Correction factor<br />

Each person has ‘his/her’ correction or insulin sensitivity factor (ISF). To calculate it you<br />

have to add all the units of insulin administered in a day (consider only insulin administered<br />

ad main meals and bedtime) and divide the constant 1800 by the total number<br />

of units. For example, if the sum of the units of insulin taken during the day is 90,<br />

1800:90 is 20, which is the correction factor. In this case, in the event of hyperglycaemia,<br />

each unit of insulin lowers the blood glucose by 20 mg/dL.<br />

Insulin sensitivity varies over time, <strong>for</strong> example during puberty, or when exercising<br />

or during the menstrual cycle. The insulin sensitivity variances are important and<br />

are taken into account by Doctors in determining the standard doses of injections, but<br />

generally they do not deteremine a significant change in the ISF. In <strong>young</strong>er children<br />

(as well as <strong>people</strong> who are more sensitive to insulin than on average), the ISF may be<br />

different at different times of the day.<br />

The correction factor allows to determine the amount of insulin required to return<br />

to normal glucose levels in case of hyperglycaemia. In order to calculate the<br />

amount of insulin required you have to subtract your target glucose value (ie. 120-<br />

150 mg/dL) from the measured value (ie. 240 mg/dL) to obtain the desired decrease<br />

in blood glucose. Assuming an ISF of 20 , the difference between the measured blood<br />

glucose level (240 mg/dL) and the acceptable level (120 mg/dL) will be divided by<br />

20 to obtain the number of units to be injected as an ‘extra dose’.<br />

The ISF is also useful in cases where the blood sugar level is less than the target<br />

value be<strong>for</strong>e meals, <strong>for</strong> example, 70 instead of 90 mg/dL. In this case, one may subtract<br />

the ‘food’ bolus by the number of units required to bring the blood glucose level<br />

to the target value. Since 90-70 is equal to 20 and the correction factor is 20, it<br />

will be sufficient to reduce by one bolus of insulin to ‘cover’ the meal and reduce the<br />

risk of hypoglycemia.


Injection areas<br />

and methods


Injection areas and methods<br />

The only minimally invasive means of administering insulin a regular and relatively<br />

unaltered absorption is by injecting it in the subcutaneous tissue <strong>with</strong> an insulin pen,<br />

syringe, of insulin pump. It is there<strong>for</strong>e fundamental to learn correct insulin preparation<br />

and injection techniques. An error in this practice may determine inadequate glucose<br />

control.<br />

Available injection devices<br />

Syringes <strong>for</strong> U-100 insulin:<br />

0.3 ml (30 U) <strong>with</strong> increments of 0.5 to 1 U, 8 mm and 30 G calibre needles.<br />

0.5 ml (50 U) <strong>with</strong> increments of 1 U, 8 mm to 12.7 mm length and 29 to 30 G calibre<br />

needles<br />

1 ml (100 U) <strong>with</strong> increments of 2 U, 8 mm to 12.7mm and 29 to 30 G calibre<br />

needles<br />

Tools<br />

U100 insulin pens (prefilled or reusable pens):<br />

<strong>with</strong> 3 ml cartridges<br />

<strong>with</strong> 4 mm, 5 mm, 6 mm, 8mm, 12.7 mm length neelds, and 28 to 33 G calibre<br />

needles<br />

<strong>with</strong> increments of 0.5, 1, and 2 U.<br />

38 )<br />

Drawing insulin <strong>with</strong> a syringe<br />

Firstly, disinfect the vial cap.<br />

Draw the desired units of air (corresponding to the amount of insulin to be injected)<br />

into the syringe.<br />

Inject the units of air into the insulin vial.<br />

Without <strong>with</strong>drawing the needle, invert the bottle and draw the units of insulin you<br />

need. At this stage it is important that there are no air bubbles in the syringe to<br />

avoid injecting air and there<strong>for</strong>e fewer units. The bubbles can be eliminated repeating<br />

the procedure or by ‘tapping’ the syringe <strong>with</strong> your finger and eliminating air<br />

by injecting out of the syringe.<br />

Cover the needle <strong>with</strong> the specific cap, being careful not to touch it <strong>with</strong> your fingers<br />

because it is sterile.<br />

Mixing two types of insulin in the syringe<br />

It is sometimes necessary to mix rapid acting <strong>with</strong> intermediate acting insulin.<br />

Firstly, sanitize the caps of both bottles.<br />

Draw a number of units of air into the syringe equal to the units of required delayed<br />

insulin.


Injection areas and methods<br />

Inject the unit of air into the delayed insulin vial.<br />

Pull the needle out and draw a number of units of air into the syringe equal to units<br />

of regular insulin requirements.<br />

Inject the unit of air into the rapid-acting insulin vial.<br />

With the needle still in the vial, turn the rapid-acting insulin vial upside down and<br />

draw the amount required, ensuring you eliminate any air bubbles in the syringe.<br />

Insert the needle into the vial of delayed insulin and draw the required units, being<br />

careful to not inject insulin back into the vial.<br />

If an excessive amount of intermediate acting insulin is drawn, the syringe must be<br />

thrown away and the procedure must be repeated <strong>with</strong> a new syringe.<br />

Cover the needle <strong>with</strong> the specific cap.<br />

If you draw the insulin from a pen cartridge (penfill) it is not necessary to inject air.<br />

The sequence described above is the correct one; the procedure must be per<strong>for</strong>med<br />

<strong>with</strong>out reversing the order in which you draw different types of insulin: first<br />

draw rapid-acting insulin, then intermediate-acting insulin.<br />

If the intermediate acting insulin is drawn first, and a small amount should be<br />

injected into the rapid-acting insulin vial, the latter would be altered and must there<strong>for</strong>e<br />

be disposed of.<br />

Injecting technique <strong>with</strong> a syringe<br />

derma<br />

subcutaneous fat<br />

( 39<br />

muscle<br />

Disinfect the area of the body you will be injecting.<br />

Remove the syringe’s cap.<br />

Softly pinch and lift the skin and subcutaneous tissue <strong>with</strong> your thumb and index.<br />

Hold the syringe like a pencil and firmly insert the needle into the skin at an angle<br />

of between 45° and 90°:<br />

injecting at 45° is recommended where there is a normal or low amount of subcutaneous<br />

tissue;


Injection areas and methods<br />

injecting at 90° is recommended where there is an abundant amount of subcutaneous<br />

tissue.<br />

Release the skin fold and draw slightly be<strong>for</strong>e injecting the insulin. This prevents you<br />

from accidentally administering insulin into a blood vessel. If blood should enter the<br />

syringe during aspiration, the syringe should be discarded and a new insulin syringe<br />

and administration area should be prepared<br />

Wait a few seconds after injecting insulin, then remove the needle and gently dab<br />

the place where the needle was inserted <strong>with</strong> a cotton swab. Do not be alarmed if<br />

a small amount of blood should appear after the needle is removed: the rupture of<br />

capillaries during needles insertion is quite common. A small bruise may also appear<br />

and is due to the presence of capillary blood in the subcutaneous tissue.<br />

40 )<br />

Injection technique <strong>with</strong> a pen<br />

Insulin pens are easy to use. They have a pen-like shape, a needle-mount, a n insulin<br />

reservoir, and a dose selector which can dial a dose <strong>with</strong> 0.5-1 Unit increments. Once<br />

the dose is selected and the injection is per<strong>for</strong>med, insulin is administerd by pressing<br />

the plunger.<br />

Injection procedure <strong>with</strong> a pen is similar to that of syringes. However, there are<br />

certain things to keep in mind:<br />

ensure there is enough insulin in the cartridge;<br />

when the cartridge (or pen) is replaced, prime the needle <strong>with</strong> a couple units (repeat<br />

until insulin exits the needle);<br />

if you are using an intermediate-acting insulin pen, turn the pen upside down 4-5<br />

times be<strong>for</strong>e using it (remember it is an insulin suspension);<br />

after pressing the plunger, wait 10 seconds be<strong>for</strong>e <strong>with</strong>drawing the needle;<br />

always change the needle after each injection;<br />

always inject at an angle of 90° when using a short 4-6 mm needle.<br />

All types of insulin are available in <strong>for</strong>mats <strong>for</strong> use in pen (pen cartridges or disposable<br />

pens). There<strong>for</strong>e, in the case of co-administration of rapid- and intermediate-<br />

acting insulin you should have either two separate pens or, if the doses are adequate,<br />

a pre-mixed pen.


Injection areas and methods<br />

Injection areas<br />

The subcutaneous tissue is placed between the skin and muscle and has the most appropriate<br />

characteristics than any other superficial tissue <strong>for</strong> the regular and consistent<br />

absorption of insulin. It also allows the administration of insulin in an almost<br />

painless procedure.<br />

Insulin can be injected in almost all areas where there is a sufficient layer of<br />

subcutaneous tissue. The following areas are particularly recommended:<br />

the abdomen, excluding the circular area (2 cm radius) around the navel;<br />

the supero-lateral quadrant of the buttocks;<br />

the anterolateral surface of the thighs;<br />

the anterolateral surface of the arms.<br />

Nel ragazzo con diabete<br />

i valori di riferimento sono i seguen<br />

tra 80 e 120 mg/dL a digiuno<br />

tra 100 e 160 mg/dL dopo i pas<br />

tra 90 e 150 mg/dL prima di corica<br />

The absorption of insulin varies from area to area (it is fastest in the abdomen<br />

and slower in the limbs and buttocks). It is there<strong>for</strong>e appropriate to use one area <strong>for</strong><br />

a specific tiem of the day to reduce variability.<br />

The injection area should be rotated on a daily basis. This is necessary to<br />

avoid the <strong>for</strong>mation of lipodystrophies, an alteration of the subcutaneous tissue induced<br />

by the repeated injection of insulin in the same area which may cause a local<br />

thickening (hypertrophy) or depressions (atrophy) of the involved subcutis. In addition<br />

to being aesthetically unpleasant, lipodystrophies cause an inadequate and irregular<br />

insulin absorption. The suspension of insulin delivery in these areas usually deteremines<br />

a full recovery of the affected area, although it might take more or less time<br />

(usually months) according to the entity of the subcutaneous alteration.<br />

Lipohypotrophies, which are essentially the loss of adipose tissue, are usually less<br />

common then hypertrophies. Lipohpotrophies are believed to be due to an immune<br />

reaction to the specific type of insulin used. There<strong>for</strong>e, switching to another insulin<br />

analog nay be useful to prevent the <strong>for</strong>mation of new lesions.<br />

( 41


Nutrition


Nutrition<br />

Nutrients<br />

The word ‘diet’ may commonly be associated to the concept sof “deprivation”, “restriction”<br />

and “sacrifice”. However, in the case of type 1 <strong>diabetes</strong>, it often simply refers<br />

to the normalization of a diet that is often unbalanced. A dietary consult <strong>with</strong> a registered<br />

dietitian may provide the necessary in<strong>for</strong>mation to set up a balanced diet, which<br />

is essential <strong>for</strong> obtaining and maintaining the psychological and physical well-being of<br />

any individual (not only <strong>people</strong> <strong>with</strong> <strong>diabetes</strong>). A regular diet should not be mistaken<br />

as a means of setting rigid rules may be hard to comply <strong>with</strong>. A regular diet must there<strong>for</strong>e<br />

be customized according to certain individual characteristics<br />

(age, weight, height, sex), work habits, physical<br />

activity and food preferences, in order to make it adequate<br />

and to satisfy individual needs. These characteristics allow<br />

you to precisely determine the energy expenditure and thus<br />

your individual caloric needs.<br />

A calorie is a unit of heat used to indicate the amount<br />

of energy that foods will produce in the human body. The<br />

amount of calories produced from food varies according<br />

to their nutrient composition. A healthy diet involves the<br />

carbohydrates 55%<br />

consumptions of adequate proportions of all nutrients. Nutrients<br />

are classified as follows:<br />

lipids 25%<br />

proteins 20%<br />

Organic substances: proteins, lipids, carbohydrates and vitamins<br />

Inorganic substances: minerals and water<br />

Proteins<br />

Proteins are used by the body <strong>for</strong> tissue repair and body mass growth. They are mainly<br />

found in foods of animal origin such as meat, fish, eggs, cheese and some vegetables<br />

such as legumes (peas, lentils, chick peas, broad beans and soybeans, etc). While it<br />

is true that these substances are essential to the body it is also true that an excessive<br />

consumption may be unhealthy.<br />

In modern day diets, in which the priority is to quickly and easily prepare a meal, there<br />

is an increased consumption of meats (especially cold cuts) and dairy products: this represents<br />

a prototype of a high-protein diet. To avoid an unbalanced diet, it is important to<br />

control the amount of protein-rich foods in main meals and snacks. Snacks do not only have<br />

the function of reducing the feeling of hunger between meals, but may also be used to<br />

prevent low blood glucose values. In this case they must provide energy that can be readily<br />

available: these include foods that are rich in carbohydrates such as fruit, bread sticks,<br />

crackers and biscuits. Foods containing high amounts of protein and fat (<strong>for</strong> example sandwiches<br />

made <strong>with</strong> cold-cut meat and cheese) require very long digestion times and there<strong>for</strong>e<br />

are not adequate in treating or preventing low blood glucose levels during the day.<br />

( 43


Nutrition<br />

Lipids<br />

Lipids or fats are the nutrients <strong>with</strong> the highest amount of calories: at the weight<br />

they provide twice as many calories as protein and carbohydrates. The dietary intake<br />

of fat is strongly linked to the use of fat as seasoning in cooking and food packaging<br />

(<strong>for</strong> example oils, butter, margarine, mayonnaise and bacon). In addition to<br />

these ‘visible’ fats we must consider the amount of those contained in foods, especially<br />

dairy products and meat. It is important to consider the percentage of saturated<br />

or unsaturated fatty acids contained in lipids. Food <strong>with</strong> a high content of saturated<br />

fatty acids are those of animal origin (butter, lard, etc.), which are difficult<br />

to digest and facilitate the deposit of fatty substances in the arteries. Lard, which is<br />

now rarely used at home, is widely used in the manufacturing of industrial products,<br />

and considerably increases the fat content of a diet. For this reason it is important<br />

to reduce the consumption of packaged products such as cakes and pizzas, replacing<br />

them <strong>with</strong> other similar home-prepared food <strong>with</strong> better quality ingredients.<br />

The fats we most recommend are those containing unsaturated fatty acids of vegetable<br />

origin (olive oil, seed oil).<br />

Carbohydrates<br />

Carbohydrates (or carbs) function as a supply of energy and are the most representative<br />

nutrient in a diets even <strong>for</strong> diabetics (about 50-60% of the total caloric intake). There<br />

is no need to reduce the total intake of carbohydrates in general except <strong>for</strong> one type:<br />

simple carbs (ex. sugar). There are in fact two types of sugar:<br />

Complex: mainly in pasta, rice, bread, breadsticks and biscuits<br />

Simple: mainly in table sugar, honey, jam, fruit, milk<br />

44 )<br />

The first group includes carbohydrates that have a complex chemical structure<br />

which require longer digestion times and do not cause quick increases in blood glucose<br />

levels. They must be consumed daily in the prescribed quantities: starting a meal<br />

<strong>with</strong> a proper portion of pasta allows you to take the amount of complex carbohydrates<br />

required to satisfy the sense of hunger and to control it <strong>for</strong> hours afterwards. Extra<br />

care must be taken regarding the intake of simple types of sugar which are responsible<br />

<strong>for</strong> rapid changes in blood glucose levels. With the exception of milk and fruit,<br />

which are recommended in a daily diet, other foods that contain high amounts of simple<br />

sugars should be avoided and their consumption must be calculated in advance.<br />

The different carbohydrate-rich foods have a wide range of absorption time. An<br />

indicator of these characteristics is called the glycaemic index (see following table).<br />

It should be emphasised that this index does not provide absolute indications since<br />

the values may be affected by cooking methods or combination <strong>with</strong> other nutrients.


Nutrition<br />

FOOD glycaemic index (%)<br />

glycaemic<br />

index<br />

glucose 100<br />

Boiled potatoes, honey 80/90<br />

Boiled rice, potatoes 70/80<br />

Brown rice, beets, bananas, raisins 60/70<br />

Oatmeal cookies, frozen peas, french fries 50/60<br />

Canned beans, peas, oranges, orange juice 40/50<br />

Chick peas, apples, yogurt 30/40<br />

Beans, lentils 20/30<br />

Soybeans, peanuts 10/20<br />

Vitamins<br />

Vitamins are a homogeneous group of substances that have the same function in<br />

terms of nutrition. The amount of vitamins that must be included in a diet varies<br />

from a few micrograms to a few milligrams. In fact, they do not have a role in processes<br />

involving energy but in bio-regulation of important chemical and hormonal<br />

processes in the body. They are classified as follows:<br />

Fat-soluble vitamins A, D, E and K<br />

Water-soluble vitamins: C and B-complex vitamins<br />

The <strong>for</strong>mer dissolve in lipids: they are in fact contained in milk, fish, egg yolk and<br />

butter. Water-soluble vitamins are found in fruit and vegetables, legumes and cereals.<br />

Vitamins are substances that are particularly delicate and to preserve them it is necessary<br />

to adequately manipulate foods that contain them. They are especially denatured<br />

by the action of light and heat, and significant mechanical processes. For this reason<br />

it is usually better to avoid juicing or cutting fruit and vegetables several hours be<strong>for</strong>e<br />

consumption, or cooking them at high temperatures <strong>for</strong> a long time.<br />

Minerals<br />

Minerals, like vitamins, are substances <strong>with</strong> a bio-regulatory function. The recommended<br />

daily amounts ranges from 100 milligrams to 1 gram <strong>for</strong> those defined as macro<br />

elements (calcium, phosphorus and sodium), and a few milligrams <strong>for</strong> those defined as<br />

trace elements (iron, zinc and iodine). A balanced and varied diet that includes fresh<br />

produce ensures an adequate intake of these substances, as well as vitamins.<br />

( 45<br />

Water<br />

Water is an essential element <strong>for</strong> life and may be drunk essentially <strong>with</strong>out limitations<br />

in the various <strong>for</strong>mulations currently on the market: natural or carbonated.


Nutrition<br />

Fibre<br />

Fibre is not considered a nutrient because it is an indigestible substance that cannot be<br />

used by the body. However, it does have important functions:<br />

it helps reduce the calorie intake resulting in an early sense of satiety;<br />

it increases the volume of intestinal contents, and there<strong>for</strong>e stimulates bowel movements<br />

and eases the elimination of digestion residues;<br />

it reduces or in any case slows down the absorption of nutrients such as sugars and<br />

cholesterol.<br />

It is contained in food of plant origin such as fruit, vegetables, legumes and whole<br />

grains. Its mechanical action is greatly reduced if the food in which it is contained<br />

is liquidized. There<strong>for</strong>e, it is advisable to consume vegetables and include wholegrain<br />

products in the diet.<br />

Classification of foods<br />

In relation to the content of nutrients, foods are classified into six basic groups<br />

<strong>with</strong> specific functions. Food substitution is necessary in relation to food belonging to<br />

the same group or food belonging to groups <strong>with</strong> similar characteristics. The six food<br />

groups are:<br />

46 )<br />

Foods<br />

dressing fats: they provide lipids<br />

meat, fish and eggs: they provide protein and vitamin B<br />

milk and dairy products: they provide protein, calcium and vitamin B<br />

cereals: they provide carbohydrates and B vitamins<br />

legumes: they provide protein, iron and vitamins<br />

vegetables and fruit: they provide sugar and pro-vitamin A, vitamin C, minerals<br />

and fibre<br />

Meat and fish<br />

Meat may be eaten daily. The so-called white meats (chicken, rabbit, turkey) have a lower<br />

fat content. Twice a week they can be replaced <strong>with</strong> beef or horse meat. Cold-cut<br />

meats should only be eaten twice a week, from among the following: cooked ham,<br />

parma ham, speck (bacon), dried beef, trimmed of visible fat.<br />

Eating fish gives the advantage of providing high-quality protein and less fat and<br />

calories than meat. The following should be avoided: salmon, eel, sardines and mackerel,<br />

since they contain more fat.


Nutrition<br />

Eggs<br />

Eggs are rich in protein and are a good substitute <strong>for</strong> meat or fish, despite having a high<br />

cholesterol content. They can be eaten twice a week.<br />

Milk and dairy products<br />

In addition to providing protein and vitamins, they are essential <strong>for</strong> calcium intake.<br />

Milk may be consumed daily, remembering that it is a food, not a beverage. Among<br />

the commercially available products you should prefer semi-skimmed milk which, while<br />

preserving the content of calcium, is less rich in fat and calories.<br />

Cheese has more fat, protein and salt than milk. There<strong>for</strong>e, it must be consumed<br />

in the right amounts two or three times a week.<br />

It is often regarded as light food to be consumed at the end of a meal but in<br />

reality its nutrient intake is high and it should be considered a real main course food.<br />

The types of cheese we most recommend are fresh and semi-fat cheeses such as: crescenza,<br />

mozzarella, quartirolo, certosina, cottage cheese, low-fat cottage cheese and<br />

smoked cheese. The ones to be avoided are those that are particularly fat or fermented<br />

such as gorgonzola, mascarpone, fontina, parmesan, Swiss cheese, taleggio, etc.<br />

FOOD PROTEIN (g) Lipids (g) Calories (kcal)<br />

Mozzarella light 20 10 172<br />

Crescenza light<br />

cheese<br />

19,4 10,3 176<br />

Mozzarella 19,9 16,1 224<br />

Caciotta 19,3 27,2 322<br />

Parmesan 27,5 28,1 363<br />

Emmenthal 29 30 386<br />

Cereals<br />

Cereals are particularly rich in complex sugars, and have a slow absorption. In particular,<br />

pasta helps blood glucose control and refrains hunger in the hours following a meal.<br />

In addition to pasta dishes, this group includes bakery products (bread sticks, crackers,<br />

biscuits, etc.), which are especially good <strong>for</strong> snacks.<br />

( 47<br />

Legumes<br />

Although legumes are plant-derived foods, they contain high-quality protein. This<br />

group includes beans, lentils, peas, chickpeas, broad beans and soybeans. They can be<br />

eaten twice a week replacing fish, meat, eggs, cold-cut meats or cheese. When they<br />

are packaged <strong>with</strong> cereals such as pasta or rice, they provide a complete meal that has<br />

protein <strong>with</strong> a biological value equal to that of meat. They are also important sources<br />

of vitamins and fibre and do not contain saturated fats or cholesterol.


Nutrition<br />

Dressings and cooking fats<br />

The fats used in the cooking of foods are made up almost entirely of lipids and are<br />

there<strong>for</strong>e particularly caloric. They are used to enhance the flavour of foods, but their<br />

uncontrolled use often causes nutritional problems that lead to overweight and alterations<br />

in blood lipids (triglycerides and cholesterol). They should be used sparingly according<br />

to the instructions provided by the diet. An easy way of dosing them is <strong>with</strong><br />

common kitchen utensils:<br />

1 tablespoon = 10 grams of oil<br />

1 teaspoon = 5 grams of oil<br />

Plant-derived fats should be prefered such as extra virgin olive oil, <strong>for</strong> it’s optimal<br />

ratio of saturated and unsaturated fatty acids especially when consumed raw. In<br />

fact, fats subject to intense heating are altered, generating substances that are toxic<br />

<strong>for</strong> the body. If you wish to use seasonings during cooking, you can contain the damage<br />

by cooking foods at low heat <strong>for</strong> a short time, and by avoiding frying or reusing<br />

the same fat.<br />

48 )<br />

Vegetables and fruit<br />

Fruit and vegetables belong to the same group because they both provide water, fibre<br />

and vitamins, but are not equivalent in terms of nutrition because of the different sugar<br />

content. Vegetables includes foods that are low in sugar and calories, and can be<br />

consumed <strong>with</strong>out having to worry about precisely controlling their quantity. Fruits include<br />

plant-derived foods which are full of simple sugar and should be consumed at<br />

specific times and in the recommended quantities. In fact they are great <strong>for</strong> snacks and<br />

<strong>for</strong> dealing <strong>with</strong> mild hypoglycaemia. They can be consumed daily and chosen from<br />

among those <strong>with</strong> less sugar: pears, apples, oranges, tangerines, mango, pomegranates,<br />

grapefruit, strawberries, blackberries, blueberries, melons, watermelons. The following<br />

should be consumed <strong>with</strong> more attention: grapes, persimmons, figs, bananas,<br />

dry exotic fruit, syrupped fruits and fruit compote.


Nutrition<br />

Sweeteners<br />

The main and most obvious principle in the treatment of <strong>diabetes</strong> is the limitation<br />

of simple sugars in general and the exclusion of common sugar (sucrose), because of<br />

its hyperglycaemic effect. Fortunately, at present the food industry offers a wide range<br />

of alternatives to sugar which can satisfy the desire <strong>for</strong> sweet things <strong>with</strong>out causing<br />

rapid changes in blood sugar levels. Being synthetic products in the majority of cases,<br />

they should be consumed <strong>with</strong> mdoeration despite their low caloric value. They can be<br />

classified into two major groups:<br />

High-intensity sweeteners<br />

Bulking agents<br />

The best known sweeteners belonging to the first group are aspartame and saccharin.<br />

Aspartame has a caloric value equal to that of sugar (about 4 calories per<br />

gram), but a sweetening power 200 times greater. There<strong>for</strong>e it is used in small quantities<br />

that do not affect blood glucose levels. It can be used to sweeten hot or cold drinks<br />

as it does not leave a significant aftertaste. Being very unstable at high temperatures,<br />

it cannot be used in the preparation of products that require cooking. Saccharin is<br />

500 times sweeter than sugar. It can also be used at high temperatures <strong>with</strong>out being<br />

altered. However, it possesses a metallic aftertaste, that may be unpleasant at times.<br />

Both of these products are so-called high-intensity sweeteners but lack volum/mass,<br />

which is especially important in the preparation of desserts, cakes and pastries. Bulking<br />

agents are sweetners that possess a mass effect. Fructose represents one of these bulk<br />

sweeteners, <strong>with</strong> a sweetening power which is twice that of sucrose. It has no particular<br />

counterindications, leaves no aftertaste, but its intake must be evaluated carefully<br />

because unlike the sweeteners described above, which have virtually no calories, it provides<br />

calories and affects your blood sugar level. The optimal solution is to use aspartame<br />

or saccharin daily to sweeten beverages and reserve the use of fructose (in controlled<br />

amounts) <strong>for</strong> the preparation of cooked sweets to be eaten occasionally. In this<br />

way it is possible to have the pleasure of enjoying a good cake <strong>with</strong>out exceeding the<br />

relevant amount of calories and causing sudden increases in blood sugar levels.<br />

( 49


Nutrition<br />

The distribution of meals<br />

In addition to knowing about foods and choosing those that are most suitable, it is<br />

important to distribute their consumption throughout the day. A balanced diet is normally<br />

distributed over three main meals and two snacks consumed regularly at midmorning<br />

and in the afternoon. The regularity of the times at which meals are consumed<br />

is of particular importance in maintaining a good metabolic balance. There<strong>for</strong>e,<br />

it is advisable to organize daily food consumption and avoid skipping or postponing<br />

one of these meals or snacks. This is the only way to optimize glucose values, control<br />

hunger, and avoid overeating at subsequent meals. Following these simple recommendations<br />

is not particularly difficult <strong>with</strong> proper nutritional education. However, these<br />

rules must be accompanied by a more specific diet plan studied in relationship to individualized<br />

needs.<br />

Carbohydrate counting<br />

Calculating carbohydrates (also called carbohydrate counting or CHO counting) is a<br />

technique that allows a more accurate assessment of the required insulin dose <strong>for</strong> a<br />

meal containing a determined quantity of carbohydrates. This allows greater freedom<br />

in terms of food choices while at the same time maintaining adequate post-meal glucose<br />

values.<br />

The basics of this technique are taught by the <strong>diabetes</strong> care team (especially<br />

by the dietician). However, a lot of “homework” is required to consolidate its practice<br />

in the first weeks/months. Periodical assessment is then per<strong>for</strong>med confirm a correct<br />

CHO counting is maintained in time.<br />

50 )<br />

The training is divided into four parts. The first and most simple part involves<br />

learning which foods contain carbohydrates. In reality it is not that simple:<br />

starchy foods and pastries are certainly among them, but so are certain legumes,<br />

fruits and vegetables, and some drinks. We need to know which recipes and preparations<br />

“hide” significant amounts of carbohydrates.<br />

The second part, which is perhaps the most difficult one, is to learn how to visually<br />

“weigh” food and beverages. It is easier <strong>for</strong> those who have some knowledge of cooking<br />

basics, but it is difficult <strong>for</strong> most <strong>people</strong>. At first it is necessary to use a scale to<br />

estimate quantities (how much does this sandwich weigh? And this portion of pasta?<br />

How much beer does this glass contain?). “Natural” measuring units are of great help:<br />

a spoon, cup, bowl, fist, and so on. Obviously you do not have to be absolutely precise:<br />

in most cases 64 g of pasta can be estimated as being 60 or 70, but if you have an<br />

error of 20g then the calculations start becoming inaccurate.<br />

How can they be calculated? Here is where the third part begins. You have to


Nutrition<br />

learn and memorize the percentage of carbohydrates contained in foods and dishes<br />

(carb counting booklets and mobile apps are also available), and the amount of<br />

carbohydrates in most common dishes that you eat. For example, uncooked spaghetti<br />

contains 80 g of carbohydrate per 100g of weight. Beer has 4 g of carbohydrate per<br />

100 g or cl.<br />

The fourth part consists of a simple multiplication. If a plate of spaghetti weighs<br />

60 g and spaghetti contains 8 g of carbohydrate per 10 g of weight, how many<br />

carbs are there on a plate? Six times eight ... <strong>for</strong>ty-eight. And there’s the result. In<br />

doing so it is possible to estimate the total amount of carbohydrates in a whole meal.<br />

Many commercial products indicate the amount of carbohydrates per 100 g of weight<br />

or per portion (but be careful to read what is meant by ‘portion’). Once you know the<br />

amount of carbohydrates, all you need to know is the carbohydrate/insulin ratio (see<br />

pages 34-35) to estimate a dose <strong>with</strong> sufficient accuracy. Let us assume that in a meal<br />

the plate of spaghetti is the only dish containing carbohydrates. Those <strong>with</strong> an insulin<br />

ratio of 12 will need a dose of 4 units to “cover” the meal.<br />

Is it really necessary to calculate these values every time you sit down to eat<br />

a meal? Only at the beginning. After a while, especially if you keep a complete blood<br />

glucose-food diary, you will find standardized solutions thanks to previous experiences.<br />

The diary is a strategic aspect. You need to methodically list what you eat<br />

(<strong>with</strong> weights) <strong>for</strong> a few weeks, quantify carbohydrates, calculate the insulin units and<br />

the change in blood glucose levels be<strong>for</strong>e and 2 hours after a meal. If it is less than 40,<br />

<strong>with</strong> a maximum of 60 mg/dL, your calculations were correct. If it is greater, something<br />

did not work. What was it? Sometimes you find out on your own. Sometimes you find<br />

out <strong>with</strong> the help of a dietician or healthcare professional.<br />

“Successful” solutions should be memorized: in the majority of cases we eat<br />

more or less a limited amount of different foods.<br />

Your grandma’s spaghetti have need 8 units. The ice cream we all eat at a<br />

bar or in a piazza on summer evenings requires 6 units. The pint of beer we drink <strong>with</strong><br />

friends requires 2 units. A “register of standard solutions” may be developed. However,<br />

it has to be updated because the portions and insulin sensitivity may change over<br />

time (think of the difference between the portions and units of a child and a teenager).<br />

( 51


Physical exercise


Physical exercise<br />

Regular physical activity is the third vital cornerstone of <strong>diabetes</strong> therapy. Regular<br />

exercise helps in to maintain cardiovascular and respiratory health, increase muscle<br />

strength, reduces the concentration of triglycerides and cholesterol, and ultimately<br />

reduces the daily insulin requirement by improving insulin sensitivity. It also helps by<br />

fostering socialization especially by practicing team sports. For these reasons, youth<br />

<strong>with</strong> Type 1 <strong>diabetes</strong> should be encouraged to practice sports – even competitive – regularly,<br />

and to enact measures to prevent glucose excursions during these activities.<br />

Obviously, only careful <strong>diabetes</strong> self-management allows the “diabetic athlete”<br />

to safely practice physical activities.<br />

When undertaking physical activity, the body generates energy by “burning”<br />

glucose; it is there<strong>for</strong>e essential to have an appropriate dose of insulin to allow glucose<br />

to enter the cells. Without insulin the glucose remains in the blood and cannot be<br />

used by muscles to produce energy.<br />

It is essential to adjust the insulin dose and sugar intake to reduce the risk of<br />

hypoglycaemia while exercising.<br />

After physical activity, the body needs to replenish its stocks of glucose, by extracting<br />

sugar from the blood. There<strong>for</strong>e, the risk of hypoglycaemia increases also after<br />

having per<strong>for</strong>med physical activities.<br />

Insulin sensitivity may increase after physical activity. This means that the same<br />

dose of insulin may have a greater effect than usual. This situation increases the risk<br />

of hypoglycaemia after exercising.<br />

A regular physical activity is strongly suggested to <strong>young</strong><br />

<strong>people</strong> <strong>with</strong> <strong>diabetes</strong>.<br />

( 53


Physical exercise<br />

What to do be<strong>for</strong>e, during<br />

and after exercise<br />

Be<strong>for</strong>e starting a planned physical activity, the following things are necessary:<br />

1. In order to prevent hypoglycemia, decrease the insulin dose that will be<br />

active during the time you will per<strong>for</strong>m physical activity.<br />

2. Fast carbohydrates <strong>for</strong> low blood glucose corrections, a glucose monitor,<br />

and insulin are to be kept nearby in order to verify and correct any<br />

glucose excursions.<br />

3. Check your blood glucose immediately be<strong>for</strong>e starting phsycial activity.<br />

Blood glucose between 100 and 180 mg/dL<br />

Take 15-20 grams of carbohydrates. Since physical most activities (especially aerobic)<br />

consume glucose, you need to “refuel” <strong>with</strong> sugar in order to have a sufficient<br />

amount of glucose available.<br />

Blood glucose > 250 mg/dL <strong>with</strong>out ketones<br />

You may practice sports after an insulin dose adinistration. In this case you<br />

have to inject an extra dose of rapid acting insulin. High blood glucose is mainly<br />

due to low insulin levels. There<strong>for</strong>e, glucose cannot enter the cells and your blood<br />

glucose will fail to drop despite physical activity.<br />

Blood glucose > 250 mg/dL <strong>with</strong> ketons<br />

54 )<br />

You should not per<strong>for</strong>m physical activity. Immediately inject a correction dose<br />

of rapid acting insulin because in this situation you are risking diabetic ketoacidosis.<br />

Wait until the injected insulin takes effect. After 90-120 minutes, check your<br />

blood glucose. If you blood glucose is <strong>with</strong>in normal range you can carry out your<br />

planned activity<br />

Blood and urinary ketones may still be positive even <strong>with</strong> a proper blood sugar<br />

level as they are eliminated from the body slowly. However, it is important to verify<br />

that they progressively reduce.<br />

Hypolycaemia<br />

Physical activity must absolutely be avoided. In this case correct it <strong>with</strong> 15<br />

g of simple carbohydrates, until the blood glucose level exceeds 100 mg/dL (see<br />

‘How to correct a hyperglycaemia’ on page 87).


Physical exercise<br />

While exercising:<br />

1. Take 15-30 grams of simple carbohydrates per hour of exercise per<strong>for</strong>med.<br />

The amount of ingested carbohydrates should be adjusted according to the blood<br />

glucose trend, type of physical activity, duration and degree of training.<br />

2. Check your blood sugar every 1-2 hours of physical activity.<br />

By measuring blood glucose while exercising you learn how your blood glucose<br />

oscillates and may determine whether the dose of carbohydrate and/or insulin<br />

administration is adequate or not.<br />

3. Drink regularly.<br />

After physical activity:<br />

1. Check your blood gluocose to verify the effectiveness of the steps you<br />

took.<br />

2. To avoid hypoglycaemia after a few hours of exercise:<br />

decrease the dose of insulin that acts during the hours of physical activity (it’s<br />

more useful <strong>for</strong> untrained <strong>people</strong>);<br />

have a carbohydrate-rich snack or meal to “refill” the body <strong>with</strong> sugar and reduce<br />

the risk of hypoglycaemia after exercising.<br />

The risk of hypoglycaemia after exercise may persist <strong>for</strong> 24-36 hours depending<br />

on the degree of training.<br />

Caution. Counter-regulatory hormones (adrenaline, glucagon, GH, cortisol etc...)<br />

are released into the bloodstream during very intense and short bouts of physical<br />

exertion such as sprinting or jumping (anaerobic activity). These hormones are able to<br />

release glucose from the liver resulting in an increase in blood glucose and there<strong>for</strong>e<br />

hyperglycaemia.<br />

During competitions, you should check your body’s adaptation to training and in<br />

particular your blood glucose trends. You should there<strong>for</strong>e monitor your blood glucose<br />

frequently--continuous interstitial glucose monitoring may in these cases be very<br />

useful. These guidelines are only a starting point and are useful to discover the individual<br />

reactions to physical stress.<br />

( 55<br />

Which sports to avoid<br />

All sports may be practiced when an adequate self-mangement is carried out. However,<br />

some must be practiced <strong>with</strong> caution: martial arts, boxing, motor racing, motorcycling,<br />

swimming solo, scuba diving, parachuting, hang gliding, bobsledding, and<br />

all those sports that expose you to harsh environmental conditions and the risk of major<br />

trauma.


Hypoglycaemia<br />

and ketoacidosis


Hypoglycaemia and ketoacidosis<br />

Hypoglycaemia<br />

This is one of the most frequent problems that a person <strong>with</strong> <strong>diabetes</strong> faces. Hypoglycaemia<br />

means thatblood glucose is below the normal range – less than 70 mg/dL.<br />

To understand hypoglycaemia you need to know how the human body works<br />

and why it requires sugar.<br />

Sugar, or rather glucose, is an important source of energy <strong>for</strong> the human body,<br />

particularly <strong>for</strong> the central nervous system, which is completely dependent on sugar in<br />

order to function. Sugar is present in many foods in the <strong>for</strong>m of carbohydrates. After<br />

being ingested, they are digested and converted into glucose, which is absorbed, thereby<br />

causing an increase in blood glucose.<br />

Tissues take the sugar they need from circulating blood glucose <strong>for</strong> energy. This<br />

occurs under the control of insulin that allows tissues, such as muscle and adipose tissue<br />

in particular, to use sugar as fuel. Insulin, however, has another important function:<br />

to stimulate the liver to accumulate sugar in the <strong>for</strong>m of glycogen, a reserve material<br />

which the organism may use whenever it is needed.<br />

If it is not replenished <strong>for</strong> a certain period of time, the glucose circulating in blood<br />

is used as energy. This determines a decrease in blood glucose levels. This also generates<br />

a decrease in insulin levels and the production of another hormone, glucagon,<br />

also of pancreatic origin, that acts in the opposite manner to insulin, releasing sugar<br />

from the deposits in the liver in order to increase the blood sugar levels. Thus, glucagon<br />

and insulin are two hormones of pancreatic origin that control the concentration<br />

of sugar in the blood in a very intricate manner.<br />

Insulin<br />

( 57<br />

Glycaemia<br />

Glucagon<br />

Adrenaline


Hypoglycaemia and ketoacidosis<br />

An imbalance between the amount of insulin and glucose in the blood can lead<br />

to blood glucose being too low (less than 50-60 mg/dL). In these cases it activates<br />

an “emergency system” that leads to the production of so-called counter-regulatory<br />

hormones: adrenaline, cortisol, growth hormone. These substances stimulate the release<br />

of sugar from the deposits and the construction of new sugar by the liver, channeling<br />

it towards the most important organs such as the brain and the heart. When<br />

this emergency system is activated, hypoglycaemia is physically perceived (see Symptoms<br />

below) and you should immediately ingest sugar. If you do not, blood glucose<br />

may continue to fall, causing symptoms of brain functioning impairment (e.g. seizures<br />

or coma).<br />

Mild hypoglycaemia<br />

Moderate hypoglycaemia<br />

Severe hypoglycaemia<br />

70 mg/dl<br />

60<br />

50<br />

40<br />

30<br />

20<br />

58 )<br />

Symptoms<br />

The clinical characteristics of hypoglycemia depends on the duration and severity of<br />

the event and may vary from mild symptoms to rare cases of coma and seizures. From<br />

a clinical point of view, hypoglycaemic episodes might be distinguished as follows.<br />

Mild hypoglycaemia: this is the most common case and occurs when your blood<br />

glucose drops below 70 mg/dL. For glucose values the body triggers a hormonal<br />

response in order to increase blood glucose levels. This hormonal response is responsible<br />

<strong>for</strong> the initial symptoms:<br />

Paleness and sweating<br />

Trembling<br />

Palpitations and an accelerated heartbeat<br />

Tingling sensation of the skin<br />

Irritability, nervousness,<br />

anxiety


Hypoglycaemia and ketoacidosis<br />

Mild hypoglycaemia is generally perceived and can be corrected by ingesting<br />

quickly ingesting fast carbohydrates, thereby resolving the problem.<br />

Moderate hypoglycaemia: when blood glucose levels continue to fall, the symptoms<br />

described above may be associated to others caused by a decrease in the concentration<br />

of glucose in the brain:<br />

Drowsiness, decreased concentration<br />

Changes in behaviour, irritability<br />

Decreased vision<br />

Confusion<br />

Fatigue<br />

Hunger<br />

Headache<br />

It is often family members or friends who notice a change in character and/or ask<br />

the youth whether they are feeling well or not. However, even in these cases it is possible<br />

to self-correct correct hypoglycaemia <strong>with</strong> consumption of fast carbohydrates.<br />

Recovery usually takes about 10-15 minutes.<br />

Severe hypoglycaemia: this is a hypoglycaemic episode in which the intervention<br />

of another individual is necessary because the person involved is physically<br />

unable to provide <strong>for</strong> him/herself. In these cases, the blood sugar level<br />

is usually less than 30 mg/dL and the patient may present the following symptoms:<br />

Slumber<br />

Inability to appropriately reply to questions<br />

If nothing is done soon, the situation may worsen leading to:<br />

Loss of consciousness<br />

Seizures<br />

Coma<br />

( 59<br />

During severe hypoglycemia, the intramuscular injection of glucagon (see below)<br />

eventually followed by the intravenous infusion of a dextrose containing solution may<br />

resolve the situation <strong>with</strong>in a few minutes. However, cases of residual neurological disorders<br />

have been described – such as difficulty in articulating words or a mild hemiparesis<br />

– which usually disappear spontaneously after a few hours.<br />

Every individual perceives hypoglycaemia in a different way. Do not worry if different<br />

symptoms appear at different times. Everyone learns to recognize his/her personal<br />

symptoms and to act accordingly. However, it is important that friends, as well as<br />

family members, are in<strong>for</strong>med of this situation and know how to recognize the symptoms<br />

of hypoglycaemia in order help when needed.


Hypoglycaemia and ketoacidosis<br />

Asymptomatic hypoglycaemia: some <strong>people</strong> do not perceive the presence of<br />

low blood glucose (40-50 mg/dL). Without warning symptoms, the correction of<br />

low blood glucose is delayed thereby increasing the risk of severe hypoglycemia.<br />

This situation may arise in two cases:<br />

<strong>people</strong> <strong>with</strong> a long history of <strong>diabetes</strong> whose counter-regulatory hormones are not<br />

triggered correctly;<br />

<strong>people</strong> who are frequently subject to hypoglycaemia. This situation leads to a reduction<br />

in the “symptoms threshold”, which means that the body gets used to a lower<br />

blood glucose level and there<strong>for</strong>e does not trigger the alarm system except <strong>for</strong> extremely<br />

low blood glucose levels.<br />

This phenomenon is perfectly reversible: <strong>with</strong> careful and prompt treatment of any<br />

hypoglycaemic episode the hypoglycaemic threshold may be brought back to normal,<br />

even though it may result in an increase in glycosylated haemoglobin.<br />

Nocturnal hypoglycaemia: hypoglycaemia may occur frequently at night and<br />

be unnoticed. Sometimes you may wake up at night <strong>with</strong> nightmares or sweating, or<br />

the following morning you may feel tired, have a headache, or find it difficult to concentrate.<br />

This type of situation may be very common and there<strong>for</strong>e should be actively<br />

pursued. This means that you must carefully monitor your blood glucose at night and<br />

per<strong>for</strong>m a blood glucose test around 2-3 a.m., the time when 75% of hypoglycaemic<br />

episodes occur.<br />

Causes of hypoglycaemia<br />

Hypoglycaemia is always caused by excessive insulin administration. Hypoglycaemia is<br />

a common occurrence and the causes can often be identified:<br />

60 )


Hypoglycaemia and ketoacidosis<br />

Causes<br />

Hypoglycae<br />

Skipping a meal or a snack, eating less than usual<br />

Incorrect use of insulin<br />

> Insulin overdose<br />

> Administration of the wrong type of insulin (rapid-acting rather than slow)<br />

> Injection in sites of lipodystrophy<br />

Unplanned intense exercise<br />

Needle inserted too deep, into the muscle<br />

Injection in a blood vessel<br />

Increased blood flow at the injection site due to overheating<br />

> Shower or hot bath after an injection<br />

> Excessive rubbing be<strong>for</strong>e or after the injection<br />

Injection practiced in an area subject to muscular ef<strong>for</strong>t<br />

Consumption of alcoholic beverages<br />

Frequency of hypoglycaemia<br />

Hypoglycaemia is common in the daily life of a child and a teenager <strong>with</strong> <strong>diabetes</strong>. Experience<br />

<strong>with</strong> continuous glucose sensors shows that the frequency is much greater<br />

than is expected. The DCCT study shows that greater metabolic control intensity inevitably<br />

results in an increase of hypoglycaemic episodes. In fact, the DCCT group of<br />

teenagers had a higher frequency of hypoglycaemia (64 episodes/100 patients/year).<br />

The development of new <strong>diabetes</strong> management tools, such as rapid- and long-acting<br />

insulin analogs, insulin pumps, and continuous glucose monitors, have made it possible<br />

to achieve a better glycosylated haemoglobin <strong>with</strong> a lower frequency of hypoglycaemia<br />

(less than 10 episodes/100 patients/year).<br />

Blood glucose tests (2-3am) are twice as important because it reduces the duration<br />

of a possible hypoglycaemic episode. This is essential as the severe consequences,<br />

such as seizures and/or death are directly proportional to the duration of hypoglycaemia.<br />

How to treat hypoglycaemia<br />

If hypoglycaemic symptoms are perceived:<br />

1. First, stop any activity you are involved in, especially if you are practicing<br />

a sport, working or driving.<br />

2. The most important thing is to always check your blood glucose: never<br />

trust your symptoms alone!<br />

3. If the value is less than 70 mg/dL, you are having low blood glucose.<br />

4. To quickly bring blood glucose levels back to normal, take 15 g of fast<br />

carbohydrate (ex. sugar). For <strong>young</strong> children or toddlers, 15 g may be too<br />

much. The amount must be calculated by multiplying the child’s weight in kg<br />

by 0.3 to obtain the number of grams.<br />

5. Check your blood glucose after 15 minutes:<br />

( 61


Hypoglycaemia and ketoacidosis<br />

if your blood glucos is below 100 mg/dL, take an additional 15 g dose of sugars;<br />

if your blood glucose is above 100 mg/dL, hypoglycaemia has been properly<br />

corrected.<br />

15 g of ordinary sugar is contained in:<br />

½ can of sugared drink<br />

½ fruit juice<br />

1 fruit juice <strong>with</strong> no added sugar<br />

3 candies<br />

2-3 sachets of sugar<br />

1 apple<br />

15 g of sugar should increase blood glucose by about 45 mg/dL (1 g of sugar increases<br />

the blood sugar level by approximately 3 mg/dL).<br />

If hypoglycaemia occurs at night or long be<strong>for</strong>e the next meal, it is better to also<br />

consume complex carbohydrates (bread sticks, biscuits, etc.).<br />

If you have low blood blucose be<strong>for</strong>e a meal, you may also reduce the insulin doses<br />

<strong>for</strong> that meal according to the correction factor.<br />

EXAMPLE: be<strong>for</strong>e meals, the blood glucose reference value is between 80<br />

and 120 mg/dL. If your blood glucose is 75 mg/dL and your correction factor<br />

is 40 mg/dL, you can reduce your meal bolus by 1 unit to decrease your<br />

blood glucose drop after a meal by 40 mg/dL.<br />

62 )<br />

Never eat sweets to correct hypoglycaemia (snacks, chocolate, cake, etc),<br />

because they take a longer time to increase blood glucose (there<strong>for</strong>e increasing low<br />

blood glucose exposure) may then raise your blood glucose excessively. If a sachet of<br />

sugar corrects hypoglycaemia in 15 minutes, a chocolate bar takes 60 minutes (fats<br />

also reduce glucose absorption).<br />

If you correct your blood glucose in the wrong way, you are likely to raise it<br />

excessively. In time this may determine an increase in your glycosylated hemoglobin.


Hypoglycaemia and ketoacidosis<br />

How to treat severe hypoglycaemia<br />

1. If the youth is partially conscious put some sugar in his/her mouth, preferably<br />

under the tongue. The sugar that is absorbed in the oral cavity will allow<br />

him/her to regain consciousness, and other fast carbohydrates may be given<br />

subsequently.<br />

2. If the situation does not improve and/or worsens (<strong>for</strong> example <strong>with</strong><br />

slumber or seizures), glucagon must be administered (1 vial <strong>for</strong> children older<br />

than 6 yrs, or ½ a vial <strong>for</strong> children under 6 years of age) by injecting it into<br />

the muscle. This injection will be effective <strong>with</strong>in 10-15 minutes and may be repeated<br />

after 30 minutes if the situation does not improve.<br />

Glucagon kits are sold in pharmacies. You must always check the expiration date.<br />

They can be stored in the refrigerator, but can be kept at room temperature <strong>for</strong> a<br />

long time (less than 20°C <strong>for</strong> 36 months, 20-30° <strong>for</strong> 3 months). Anyone <strong>with</strong> <strong>diabetes</strong><br />

needs to have at least one glucagon kit at home. Glucagon can cause side effects such<br />

as nausea and vomiting. In this case give cold sweet drinks in small sips every 5-10<br />

minutes. Glucagon may have e lesser effect if the hypoglycaemia is caused by alcohol<br />

abuse – in this situation it is necessary to go to the nearest emergency department <strong>for</strong><br />

the intravenous infusion of glucose.<br />

3. In any case, if you are unable to improve the situation, it is better to<br />

reach the nearest emergency department, where intravenous dextrose may<br />

be administered to resolve the event.<br />

N.B. Patients who are unconscious should never be given oral carbohydrates<br />

(fluid or solid) as there is a risk of inhaling and consequently worsening the<br />

situation.<br />

People <strong>with</strong> <strong>diabetes</strong> should always carry simple carbohydrates <strong>for</strong> a prompt<br />

correction of hypoglycemic events. It is also suggested to carry a medical identification<br />

card (pendant or bracelet) that may be useful <strong>for</strong> rescuers in case of loss of consciousness.<br />

( 63<br />

Preventing hypoglycaemia<br />

The day after the occurrence of an unexplained hypoglycaemic episode, make a<br />

10% reduction in the dose of insulin that is active in the time period in which the<br />

low blood glucose occurred.<br />

In the case of sports activities you should have a small snack or reduce the dose of<br />

insulin (as explained in the previous chapter).


Hypoglycaemia and ketoacidosis<br />

Prefilled <strong>with</strong> dilutant<br />

Inject dilutant<br />

in glucagon vial<br />

Keeping the syringe<br />

in place, shake<br />

slightly to allow<br />

<strong>for</strong> full dilution.<br />

Draw to take<br />

diluted<br />

mix back into<br />

syringe.<br />

Inject mix, in thigh<br />

or gluteal muscles<br />

preferably, or<br />

alternative muscle<br />

spots should<br />

the <strong>for</strong>mer be<br />

unavailable.<br />

64 )<br />

In the presence of intermittent illness during which a child or adolescent is lacking<br />

appetite, administer ultrafast insulin after the child has consumed the meal (to be<br />

sure of how much they are eating and to prevent an excess of insulin administration)<br />

and/or reduce the dose.<br />

If you plan to drink alcoholic beverages, first of all do not abuse it (excessive alcohol<br />

consumption increases the risk of hypoglycemia and may prevent blood glucose<br />

from rising). Remember to monitor your blood glucose regularly and consume carbohydrates<br />

(simple or complex) when needed.<br />

Continuous glucose monitors (CGMs) are new tools <strong>for</strong> the prevention of glucose<br />

excursions (low and high blood glucose). They possess alarms <strong>for</strong> thresholds (e.g.<br />

70 mg/dL <strong>for</strong> lows and 200 mg/dL <strong>for</strong> highs) as well as <strong>for</strong> trends, and hypo-/hyperglycaemia<br />

predictors. The alarms are represented by acoustic and vibration alerts. However,<br />

recent studies show that patients do not perceive 75% of alarms.<br />

In addition, newer insulin pumps may also integrate the in<strong>for</strong>mation supplied by<br />

CGMs and may automatically suspend insulin delivery in case of a CGMs hypo alerts.<br />

These instruments have may determine a significant reduction in hypoglycaemia<br />

and improve metabolic control.


Hypoglycaemia and ketoacidosis<br />

Ketoacidosis<br />

This term defines a condition characterised by increased blood acidity caused by the<br />

accumulation of ketone bodies.<br />

This situation occurs when the cells burn fat because they are unable to use glucose<br />

as the main source of energy. This results in the production ketone bodies, substances<br />

that are toxic <strong>for</strong> the body and that may accumulate in the blood (ketonemia) causing<br />

an increase in acidity. This waste product is eliminated from the blood in the urine<br />

(acetonuria) and in exhaled air, giving breath an acetone odour.<br />

Causes<br />

Lack of insulin: this situation occurs at the onset of <strong>diabetes</strong> be<strong>for</strong>e insulin therapy<br />

is undertaken.<br />

Insufficient insulin administration: this happens to <strong>people</strong> who do not properly manage<br />

<strong>diabetes</strong> (<strong>for</strong> example skipping insulin doses) or specific situations such as intermittent<br />

illnesses (in which insulin doses must be adjusted).<br />

Signs and symptoms<br />

Hyperglycaemia<br />

Glycosuria: due to the inability of cells to use blood glucose, the latter accumulates<br />

in the blood, exceeding the renal threshold<br />

Acetonuria: excess waste is eliminated in the urine<br />

Signs<br />

Symptoms<br />

Acetone breath odour: the excess waste is eliminated in exhaled air<br />

Dehydration: due to excessive fluid loss (osmotic diuresis) <strong>with</strong> frequent urination<br />

Weight loss: due to the consumption of fat tissue<br />

Vomiting<br />

Increased depth and rate of respiration<br />

Unconsciousness<br />

The presence of acetone in the urine or blood in association <strong>with</strong> frequent<br />

hyperglycaemia is a warning: you must not delay in taking remedial action. Diabetics<br />

should never have acetone in the urine or acetonemia <strong>with</strong> a value greater than<br />

0.6 mmol/L. Using the specific strips to detect the presence of ketones is important to<br />

prevent the onset of ketoacidosis and <strong>for</strong> monitoring the situation over time, in particular<br />

in risk situations such as in intermittent infections.<br />

If you are experiencing the onset of hyperglycaemia and acetonuria or acetonemia,<br />

action should be taken immediately by the administration of additional doses<br />

of short-acting insulin (bolus equal to 10% of the daily dose) and consult a Doctor<br />

as soon as possible. Ketoacidosis is a serious situation and needs to be treated in<br />

hospital as soon as possible.<br />

( 65


Long-term<br />

complications


Long-term complications<br />

Maintaining adequate glucose control allows you to reduce the risk, delay the onset<br />

and/or slow the progression of so-called complications correlated to <strong>diabetes</strong>. People<br />

<strong>with</strong> <strong>diabetes</strong> are more likely to develop eye, renal and peripheral nerve damage as a<br />

result of poorly controlled <strong>diabetes</strong>.<br />

Fifty percent of patients <strong>with</strong> type 1 <strong>diabetes</strong> do not develop complications,<br />

even after over 20 years of disease, thanks to well-managed treatment. The complications<br />

are not related to <strong>diabetes</strong> per se but are directly proportional to the exposure<br />

to hyperglycaemia.<br />

Optimal glucose control significantly reduces the risk of complications in the<br />

short and long term: in fact, poor metabolic control determines a four-fold increase<br />

in the risk of complications.<br />

If detected early, complications can be treated effectively. Currently, therapeutic<br />

novelties provide us <strong>with</strong> new opportunities and the ability to achieve near-normal<br />

glucose control. These tools theoretically allow us to achieve a complete prevention<br />

of complications (which do not develop <strong>with</strong> glycosylated haemoglobin < 6.5%). This<br />

is why the goal of insulin therapy is to expose diabetics to high glucose levels (>180<br />

mg/dL) as little as possible.<br />

It is in your interest to read and learn about all the problems that may be correlated<br />

to <strong>diabetes</strong>. The content of this handbook will help find the right reasons to convince<br />

you to avoid the risk of complications.<br />

( 67


Long-term complications<br />

Microvascular complications<br />

Microvascular complications are caused by an alteration of the small blood vessels<br />

(microangiopathy) secondary to elevated exposure to high blood glucose levels.<br />

Microvascular complications: eyes (retinopathy), kidneys (nephropathy) and nerves<br />

(neuropathy).<br />

Retinopathy<br />

The eyes of a person <strong>with</strong> <strong>diabetes</strong> may suffer damage to the retina, a tissue located<br />

in the back of the eye that has the function of receiving the images and transmitting<br />

them to the brain via the optic nerve. The retina is nourished by capillaries nutrients<br />

and oxygen which are necessary <strong>for</strong> its function. Retinopathy occurs when these capillaries<br />

are damaged due to unstable or continuously high blood glucose levels.<br />

The process that leads to the deterioration of the retina has three phases:<br />

the walls of small blood vessels dilate and become more fragile, <strong>for</strong>ming microaneurysms<br />

they subsequently become permeable and first let liquids cross the capillary wall,<br />

causing the <strong>for</strong>mation of edema, and then red blood cells, causing small hemorrhages.<br />

These two processes slows circulation and promotes the development of blood clots<br />

that block capillary blood flow<br />

there<strong>for</strong>e, the retina stimulates the <strong>for</strong>mation of new capillaries which are more fragile<br />

and more easily damaged, causing further bleeding<br />

Main visual consequences of retinopathy are:<br />

Image distortion<br />

black or red spots or cobwebs<br />

decreased vision<br />

retinal detachment<br />

68 )<br />

Retinopathy<br />

If the onset of visual impairment is not followed by a period of improved metabolic<br />

control and an eye examination, retinopathy may progress leading to blindness.<br />

By per<strong>for</strong>ming a fundus oculi examination and fluorescein angiography, ophthalmologists<br />

may now even detect small and early capillary alterations. Even drug therapies<br />

have also recently emerged.<br />

The early changes of diabetic retinopathy are reversible by beginning an adequate<br />

<strong>diabetes</strong> management. However, when this is not possible or is not enough, laser<br />

treatment may be per<strong>for</strong>med on damaged capillaries and reduce visual impairment.<br />

The only way to detect early retinal changes (when symptoms of impaired sight have<br />

not yet emerged) is to per<strong>for</strong>m annual fundus examinations.


Long-term complications<br />

A careful fundus examination once a year may prevent very<br />

serious problems.<br />

Nephropathy<br />

In the past this was the most frequent complication (30-35%) among <strong>people</strong> <strong>with</strong><br />

long-lasting <strong>diabetes</strong>. It is caused by damage to the small blood vessels that supply<br />

blood to the kidneys as a result of persistently elevated blood glucose levels.<br />

The kidneys have the function of filtering out toxic or excess substances from the<br />

blood and reabsorbing substances that are instead useful <strong>for</strong> the bod. There<strong>for</strong>e, each<br />

kidney has a membrane <strong>with</strong> many holes which acts as a filter. A small protein called<br />

albumin passes through this membrane.<br />

In the presence of initial capillary and kidney damage, the holes widen, allowing a<br />

greater amount of albumin to pass: this is called microalbuminuria. This situation<br />

can be reversed, by reestablishing adequate glucose control and in some cases <strong>with</strong><br />

the use of specific anti-hypertensive drugs (nephropathy is often associated <strong>with</strong> a<br />

rise in blood pressure).<br />

If this situation is not properly treated or investigated, the membrane allows the passage<br />

of larger proteins, leading to persistent proteinuria.<br />

If this damage continues, the kidney filtering capacity of reduces and may progress<br />

to kidney failure.<br />

Currently the incidence of nephropathy has decreased compared to the past, due to<br />

early diagnosis and annual screening <strong>for</strong> microalbuminuria, as well as the possibility to<br />

treat it properly. This is also in relationship to better current self-management of <strong>diabetes</strong><br />

during childhood, improved doctor-patient relationships, and the availability of<br />

precise means <strong>for</strong> self-monitoring of blood glucose at home. It is suggested test <strong>for</strong><br />

microalbuminuria at least once a year and always promptly treat any urinary tract<br />

infections in order to eliminate other causes of renal damage.<br />

As <strong>with</strong> retinopathy, a careful managemenet of blood glucose reduces the risk of<br />

nephropathy and, even when microalbuminuria is already present, it allows to delay<br />

the progression to permanent kidney damage.<br />

( 69<br />

Neuropathy<br />

The metabolic changes caused by poor glycaemic control are also responsible <strong>for</strong> damage<br />

to the peripheral and vegetative nervous system.<br />

Peripheral neuropathy<br />

Peripheral nerves, such as those in the upper and lower limbs, are those most affected<br />

by this type of disease.


Long-term complications<br />

Nerve damage evolves in two stages that can be distinguished on the basis of the<br />

patient’s symptoms and nerve functioning tests.<br />

1 st stage: functional tests are positive but there are no symptoms<br />

2 nd stage: functional tests are positive and there are symptoms:<br />

> tingling and a painful stinging sensation<br />

> muscle cramps<br />

> reduction of thermal sensitivity, which is painful and vibratory<br />

Neuropathy is responsible, alongside a reduced blood blood flow (vascular complications),<br />

<strong>for</strong> the diabetic foot, which facilitates the onset of accidental injuries/lesions<br />

due to reduced sensitivity and impaired healing. There<strong>for</strong>e it is also easier to have<br />

infections in the affected limb to too poor circulation.<br />

However, the diabetic foot only develops in <strong>people</strong> <strong>with</strong> long lasting and poorly<br />

controlled <strong>diabetes</strong>. It may nonetheless be prevented also by following a few precautions<br />

such as wearing com<strong>for</strong>table shoes and correct pedicure.<br />

Autonomic neuropathy<br />

This term refers to the damage to the nerves that serve internal organs, such as the<br />

heart and gastrointestinal tract.<br />

This kind of complication, which occurs after many years of poorly controlled<br />

<strong>diabetes</strong>, may be identified by the following symptoms:<br />

lowering of blood pressure during changes in position<br />

increased heart rate and abnormal heart function<br />

slowed gastric and esophageal emptying<br />

occasional diarrhoea alternating <strong>with</strong> constipation<br />

incomplete emptying of the bladder<br />

impotence<br />

70 )<br />

Neuropathy


Long-term complications<br />

Macrovascular complications<br />

Complications affecting the large blood vessels may determine poor blood flow to the<br />

heart (myocardial infarction) and brain (stroke). These circulatory deficits occur <strong>with</strong><br />

greater frequency in the diabetic population <strong>with</strong> poor metabolic control.<br />

The main cause of deterioration is macrovascular atherosclerosis. The arteries,<br />

vessels that carry oxygenated blood from the heart to the rest of the body, are progressively<br />

occluded by the gradual thickening of the arterial walls due to high blood<br />

glucose and lipids. There<strong>for</strong>e, the tissues receive an insufficient supply of oxygen and<br />

nutrients and undergo ischemia. The obstruction of the coronary arteries reduces the<br />

hearts’ blood supply causing myocardial suffering which may progress to myocardial<br />

infarction – the same happens in cerebral vessels, causing a stroke.<br />

This can happen to <strong>people</strong> of any age, but the <strong>people</strong> most at risk are smokers,<br />

<strong>people</strong> <strong>with</strong> a sedentary lifestyle and those who are overweight.<br />

Useful tips to reduce the risk of any type of complication:<br />

careful self-monitoring of blood glucose levels and ketonuria/ketonemia<br />

check-up visits on a quarterly basis as an outpatient at a <strong>diabetes</strong><br />

healthcare centre<br />

annual inspection of the fundus<br />

periodically check blood pressure<br />

checking the value of blood lipids (cholesterol and triglycerides)<br />

following a proper diet plan and maintaining an adequate body mass index<br />

per<strong>for</strong>ming regular physical activity<br />

stop smoking: cigarette smoke increases the risk of cardiac and vascular damage,<br />

in addition to causing lung cancer.<br />

Well-controlled <strong>diabetes</strong> may reduce the risk of complications<br />

to the point of eliminating them.<br />

( 71


Insulin pumps


Insulin pumps<br />

What is an insulin pump?<br />

A insulin pump is a device that continuously delivers rapid-acting insulin analogs,<br />

thereby replacing multiple daily injections. The pump allows you to better mimic the<br />

physiological pancreatic insulin secretion.<br />

The pump is a programmable device <strong>for</strong> administration of a continuous flow of<br />

basal insulin. The amount of basal insulin is initially established <strong>with</strong> the aid of a <strong>diabetes</strong><br />

healthcare team and is tailored to the person’s daily needs. The basal rate of insulin<br />

can be programmed <strong>with</strong> different hourly rates depending the insulin requirements<br />

at different times of the day.<br />

A dose of insulin is manually administered through the pump be<strong>for</strong>e each meal<br />

or snack as one would do <strong>with</strong> inejctions. The pump is equipped <strong>with</strong> an insulin cartridge/reservoir.<br />

Insulin is pumped from the reservoir through the infusion set, consisting<br />

of a thin tube <strong>with</strong> a small flexible cannula on the end. The latter is inserted into<br />

the subcutaneous tissue of the abdomen by means of a needle, which is then removed,<br />

and fastened <strong>with</strong> a plaster.<br />

This small device can be clipped onto your belt or kept in a pocket; there are a<br />

number of cases, even waterproof ones.<br />

The operation of the pump is controlled by a display that shows each type of<br />

programmed function. The pump has acoustic alarms and error reporting functions. It<br />

may also be turned on and off or removed at any time of the day.<br />

Pump use does not determine any kind of limitation in daily activities. It provides<br />

more flexibility during the day as it eliminates the need <strong>for</strong> multiple injections and the<br />

carrying of injection material (pen, vials, needles, syringes).<br />

Using an insulin pump requires motivation towards a more frequent blood glucose<br />

monitoring and involves specific education (defined as second level education)<br />

prior to its use.<br />

( 73


Insulin pumps<br />

Inclusion criteria<br />

In our centre, the patient must be in the following condition in order to use a pump:<br />

be able to properly per<strong>for</strong>m intensive insulin treatment, including the correct management<br />

of hypo and hyper glycaemia; be able to accurately count carbohydrates<br />

and have no psychological barriers preventing the attainment of adqequate metabolic<br />

control.<br />

If properly managed, the pump allows a reduction of mean blood glucose and<br />

there<strong>for</strong>e glycated hemoglobin (by an average of 0.2-0.5 %) and a better distribution<br />

of blood glucose levels <strong>with</strong> a lower number of blood glucose readings below 70 and<br />

above 180 mg/dL. Meta-analyses in literature suggest that the insulin pump allows a<br />

significant reduction of hypoglycaemia, particularly severe hypoglycemia.<br />

However, there are risks that are correlated to this kind of insulin administration.<br />

In particular, diabetic ketoacidosis may have a rapid onset due to the an interruption<br />

of insulin infusion (ie. due to needle or catheter obstruction). For this reason, the use<br />

of an insulin pump requires careful self-monitoring through frequent blood glucose<br />

and ketone tests. There are specific rules of conduct <strong>for</strong> hyper- and hypoglycaemia<br />

that should be followed meticulously to limit the rare but possible risks of connected<br />

to pump us. A continuous glucose monitoring device may help in the establishment<br />

of a more precise insulin pump.<br />

How it works<br />

74 )<br />

The insulin pump is a device that allows you to receive subcutaneous insulin 24 hours<br />

a day. The pump has certain basic components:<br />

a small computer <strong>with</strong> software and memory<br />

a display<br />

an electric motor<br />

an insulin reservoir.<br />

The pump is connected to the subcutaneous tissue through a small tube (catheter)<br />

and a subcutaneous cannula. Insulin is infused under the skin: in other words in<br />

the same area in which insulin is administered by injection. The pump administers insulin<br />

subcutaneously in small doses (micro-doses) continuously <strong>for</strong> 24 hours a day.<br />

The device remains continuously connected to the subcutaneous tissue, <strong>with</strong> the<br />

exception of periods of disconnection, which can last up to 2 hours (see ‘Temporary<br />

Disconnection’ on page 79).


Insulin pumps<br />

Self-monitoring<br />

People who use the pump must check their blood sugar levels frequently (at least<br />

6 times a day), because the insulin pump only administers rapid-acting insulin analogs,<br />

and in case of malfunctioning the body remains <strong>with</strong>out insulin <strong>with</strong>n a few<br />

hours from the interruption of insulin infusion. The only way to be promptly aware of<br />

any kind of malfunction is by measuring your blood glucose at regular time intervals.<br />

In order to verify the actions and decisions you take, the data should be recorded<br />

in a ‘blood glucose diary’ that must include the following:<br />

daily blood glucose levels trend<br />

insulin boluses <strong>for</strong> meals and correction<br />

amount of carbohydrate consumed<br />

sports practiced<br />

possible presence of ketonemia<br />

possible change of infusion set<br />

any additional useful notes.<br />

The insulin pump diary there<strong>for</strong>e allows you to have quick summary of decisions<br />

and activities that have been carried out during the day. All this in<strong>for</strong>mation (which<br />

translates to experience) is helpful to improve blood glucose in the future.<br />

The infusion set<br />

The infusion set is a set of components that connects the insulin reservoir of the pump<br />

to the subcutaneous tissue.<br />

The insulin reservoir<br />

The insulin reservoir is a special fillable cartridge that fits into an insulin pump. By means<br />

of a piston drived by the pump’s motor, insulin is “pumped” through the infusion<br />

set to the subcutaneous tissue. Obviously, the reservoir must be filled immediately be<strong>for</strong>e<br />

you use the pump and everytime an infusion set change is required. This procedure<br />

involves the following:<br />

firstly, you must take particular care <strong>with</strong> hygiene during all procedures to avoid<br />

contaminating the insulin that will be administered by the pump.<br />

you must avoid creating air bubbles when filling the reservoir; it is useful to remove<br />

the vial of insulin from the refrigerator a few minutes be<strong>for</strong>e filling the reservoir.<br />

check that the plunger of the reservoir is moving properly <strong>with</strong>out abnormal resistance<br />

if air bubbles are <strong>for</strong>med in the reservoir, the pump will administer air instead of insulin,<br />

<strong>with</strong> the result of obtaining high blood glucose levels. There<strong>for</strong>e, you need to<br />

( 75


Insulin pumps<br />

check that there are no air bubbles in the reservoir and, if present, you have to eliminate<br />

them. Air bubbles are not dangerous in themselves because they end up in<br />

the subcutaneous tissue and not in the bloodstream. They can be avoided of by turning<br />

the pump <strong>with</strong> the catheter pointing downwards (“upside down”) any air bubbles<br />

will settle on the plunger and will not be infused un less the pump is turned<br />

back around.<br />

the infusion set (including the reservoir) should be replaced every 2-3 days, even if<br />

the reservoir is not empty. The pump is able to activate an alarm when the reservoir<br />

contains just a few units of insulin.<br />

Do not stay “in reserve”<br />

If the insulin reservoir is empty, the pump cannot infuse insulin subcutaneously. To<br />

avoid being left <strong>with</strong> an empty insulin reservoir you must:<br />

always check there is a sufficient amount of insulin remaining in the reservoir be<strong>for</strong>e<br />

you leave home<br />

replace the insulin reservoir as soon as the empty reservoir alarm sets off<br />

Set the alarm parameters in the reservoir to a level which allows a sufficient dose of<br />

insulin (e.g. 20U).<br />

The reservoir is connected to the catheter by means of an adapter, which must<br />

be securely screwed on to prevent insulin from leaking.<br />

76 )<br />

The catheter<br />

The catheter connects the reservoir of insulin to the subcutaneous cannula. The insulin<br />

catheter has two tubes inserted into one another: the outer one is round but the<br />

insulin flows through the inner catheter which, to be more resistant, has is star-shapeed.<br />

This makes the catheter resistant to compression, stretching and knots. Since<br />

the catheter is transparent, you can see whether an air bubble has <strong>for</strong>med in the inner<br />

tube.<br />

Air bubbles are a problem because air may be infused instead of insulin. A 2.5 cm<br />

long air bubble covers the space reserved <strong>for</strong> 0.5 units of insulin. With a 2.5 cm long<br />

air bubble, those who take insulin at a rate of 0.2 units per hour will remain <strong>with</strong>out<br />

insulin <strong>for</strong> two and a half hours.<br />

Insulin and the catheter material are not completely compatible, which may result<br />

in the <strong>for</strong>mation of insulin precipitates which block or significantly reduce the<br />

flow of insulin. For this reason it is necessary to change the catheter every 2-3 days,<br />

even if it works regularly, or whenever there is any doubt as to whether it is working<br />

properly.<br />

There are catheters of different lengths, and you can choose the length you find<br />

most suitable. The catheter is connected mechanically to the cannula under the skin.<br />

You can remove the catheter from the cannula whenever you wish to.


Insulin pumps<br />

The cannula<br />

The subcutaneous cannula allows the passage of insulin to the subcutaneous tissue.<br />

From this tissue, insulin is then absorbed in the bloodstream and is distributed throughout<br />

the body. The insertion areas <strong>for</strong> cannulas under the skin are the abdomen (preferred<br />

area) and buttocks.<br />

Insertion of the cannula<br />

The cannula is inserted subcutaneously using a needle that acts as a guide. This can<br />

be done manually or by using appropriate insertion devices.<br />

Once positioned, the needle is removed and the cannula remains in position in<br />

the subcutaneous tissue. The cannula is then attached to the skin by means of a plaster<br />

that prevents it coming loose. The cannula is made of flexible material and does<br />

not cause pain. There are vertical and oblique cannulas. There are tubes of varying<br />

lengths, so you can choose the one you find most suitable.<br />

To prevent skin infections, be careful to disinfect the chosen insertion area be<strong>for</strong>e<br />

placing the cannula.<br />

If you see or feel signs or symptoms of infection or inflammation (redness, swelling,<br />

pus, itching, etc.) in the insertion side, you must immediately:<br />

remove the cannula<br />

clean the area where it is inserted<br />

apply an antibiotic and local anti-inflammatory ointment.<br />

The risk of infection is higher if you keep the cannula in the same place <strong>for</strong> more<br />

than three days. This is another reason why it is necessary to change the insertion<br />

area at least every three days.<br />

The cannula insertion determines a micro trauma in the skin and <strong>for</strong> this reason<br />

micro-scars may remain visible. If this happens, it is important to change the cannula<br />

every 2-3 days and check the insertion procedure.<br />

Other technical in<strong>for</strong>mation<br />

The pump is powered by batteries. Ensure they are charged and replace them over time.<br />

The pump is waterproof (different pumps have different degrees of waterproofness).<br />

If the pump is in perfect condition, water droplets or temporary immersions<br />

are not a problem. Since you can temporarily disconnect the pump, it is preferable to<br />

avoid dipping it into water to avoid potential damage or malfunctions.<br />

The pump has a “key lock” function that avoids the risk of accidentally activating<br />

certain functions.<br />

( 77


Insulin pumps<br />

Basal insulinization<br />

The pump administers insulin subcutaneously in two ways: basal and bolus. Basal<br />

insulin consists of insulin microboluses administered continuously. For example, 0.5<br />

units/hour (U/h) is equivalent to the administration <strong>with</strong>in one hour of 0.5 units of insulin,<br />

‘broken down’ into micro-boluses administered every few minutes. The amount<br />

of basal insulin corresponds to the need <strong>for</strong> insulin during fasting and in resting conditions.<br />

The term used is ‘basal rate’, because the pump is a machine that pushes insulin<br />

in a certain amount of time: like a car traveling at 50 or 100 km/h, a pump pushes<br />

insulin at a rate of 0.4 U/h or 0.8 U/h.<br />

The pump allows you to change the rate of administration of basal insulin during<br />

the daily 24 hours, covering different insulin needs during fasting and resting periods.<br />

Using the pump, you can program different daily regimens of basal infusion called<br />

to meet different needs. For example, you can use a standard basal rate during<br />

certain days and another in the days when you practice sports, or one specially planned<br />

<strong>for</strong> the weekend.<br />

When the term ‘basal insulin’ is used you must keep in mind that this is not a particular<br />

type of insulin, but the way the pump is admistering it.<br />

78 )<br />

How and when to change the basal insulin rate<br />

If the blood sugar level increases during a period of fasting or resting, you have to increase<br />

the amount of basal insulin, and thus increase the basal rate to make sure that<br />

blood glucose levels remain stable. If your blood glucose decreases during a period of<br />

fasting or resting, you should administer less insulin, to make sure that blood glucose<br />

remain stable.<br />

It is important to remember that when you change the basal insulin rate, the insulin<br />

concentration in the blood will slowly change. This is why it is necessary to increase<br />

or reduce the rate of basal insulin 1-2 hours be<strong>for</strong>e the previously identified rise<br />

or decrease in blood glucose.<br />

If blood glucose is not in the target range after a meal (up to 4 hours after a<br />

meal), you must change the meal bolus insulin.<br />

If blood glusoe is not stable during fasting and in the absence of physical activity,<br />

you have to change the basal insulin rate.<br />

To check whether the fasting and resting blood glucose level is stable, you must:<br />

check blood glucose at least twice<br />

compare the values and see if your blood glucose has risen, decreased or remained<br />

stable.<br />

It is not sufficient to evaluate only one glucose value alone. You must instead<br />

consider the comparison between two subsequent blood glucose tests. Blood glucose<br />

is considered stable if the variation in the blood glucose is less than ±30-40 mg/dL.


Insulin pumps<br />

Blood glucose level Basal rate Glucose trend<br />

12 a.m. 2 a.m.<br />

Example 1) 210 230 STABLE OK<br />

Example 2) 210 290 UNSTABLE too little<br />

Example 3) 210 120 UNSTABLE too much<br />

5 p.m. 7 p.m.<br />

Example 4) 130 121 STABLE OK<br />

Example 5) 130 193 UNSTABLE too little<br />

Example 6) 130 85 UNSTABLE too much<br />

In example No. 1, there is a blood glucose of 210 mg/dl at 12 a.m. and 230 mg/<br />

dL at 2 a.m. (increased by 20 mg/dL): the glucose trend is stable and there<strong>for</strong>e the basal<br />

insulin in that time frame is correct.<br />

In example No. 2, there is a blood glucose of 210 mg/dL at 12 a.m. and 290 mg/<br />

dL at 2 a.m. (increased by 80 mg/dL ): the glucose trend is unstable and there<strong>for</strong>e the<br />

basal insulin in that time frame is not sufficient. There<strong>for</strong>e, the basal insulin rate must<br />

be increased starting from 12 a.m. .<br />

In example No. 6, there is a blood glucose of 130 mg/dL at 17.00 and 85 mg/<br />

dL at 19.00 (reduced by 45 mg/dL): the glucose trend is unstable. There<strong>for</strong>e, there is<br />

too much basal insulin in that tiem frame. You must reduce the basal insulin starting<br />

from 5 p.m.<br />

The basal rate is increased or decreased by 0.1 U/h if ongoing basal rate is greater<br />

than 0.5 U/I or by 0.05 U/h ongoing basal rate is less than 0.5 U/h.<br />

The temporary basal rate<br />

The pump allows you to temporarily increase or decrease the dose of basal insulin <strong>for</strong><br />

a given time, <strong>with</strong>out changing planned basal rate settings. This is called the temporary<br />

basal rate (or “temporary basal”): the rate of basal insulin infusion is increased<br />

or decreased according to a transitory necessity <strong>for</strong> a predetermined period of time.<br />

To use this function you have to decide:<br />

whether to increase or decrease the scheduled basal insulin rate<br />

by what percentage you should increase or decrease the scheduled basal insulin rate<br />

how long this temporary variation must last.<br />

( 79<br />

For example, if you continue to experience hypoglycaemia (<strong>for</strong> example during<br />

the night or during a prolonged physical activity), the planned basal rate can be reduced<br />

by 50% <strong>for</strong> 4 hours. With this function, you do not run the risk of changing the<br />

basal insulin rate <strong>for</strong> a transitory necessity, subsequently <strong>for</strong>getting to return to the<br />

usual basal rate settings.


Insulin pumps<br />

Basal insulin suspension<br />

If you stop the administration of insulin at a given time, insulin will still be available<br />

<strong>for</strong> approximately the next 3-4 hours. Subsequently, when the subcutaneous insulin<br />

deposit is consumed, the body will be lacking insulin. Without insulin glucose remains<br />

in the blood and cannot be used by the cells to produce energy.<br />

The cells in your body will “burn” fat to create energy. This process will lead to<br />

the accumulation of ketone bodies in the blood and urine. To verify this situation, measure<br />

the blood glucose and ketone levels (see “ketones”). In case of prolonged lack<br />

of insulin, there is an increased risk of a diabetic ketoacidosis if insulin administration<br />

is not promptly recommenced.<br />

Temporary disconnection<br />

In some cases it is possible to disconnect the pump from the cannula. This may be necessary,<br />

<strong>for</strong> example if you are having a bath, shower, practicing sports <strong>with</strong> physical<br />

contact, changing the set or <strong>for</strong> other needs. The maximum disconnection time is 2<br />

hours. After this time, you should reconnect your pump or administer insulin <strong>with</strong> a<br />

syringe or pen, so as to prevent your body from remaining <strong>with</strong>out insulin.<br />

80 )<br />

In order to disconnect the pump <strong>for</strong> a short time (less than 1 hour), you<br />

must:<br />

check your blood glucose<br />

disconnect the catheter from the cannula<br />

protect the cannula and catheter extremities <strong>with</strong> their specific cap<br />

do not suspend the pump infusion to avoid insulin from precipitating and occluding<br />

the catheter (there is an increased risk of insulin crystals <strong>for</strong>mation when the flow is<br />

interrupted)<br />

at the end of the disconnection period, connect the catheter to the cannula and<br />

check your blood glucose<br />

if necessary, correct an eventual high blood glucose <strong>with</strong> a bolus of insulin, applying<br />

the insulin sensitivity factor (also called the correction factor, see page 35).<br />

EXAMPLE: Be<strong>for</strong>e you take a shower, measure your blood glucose level,<br />

disconnect the catheter from the subcutaneous cannula, protect the cannula<br />

<strong>with</strong> its specific cover, keep the pump in operation, and reconnect the<br />

catheter to the cannula when you have finished showering.


Insulin pumps<br />

When pump disconnection exceeds one hour (maximum 2h), you should administer<br />

a small insulin bolus to replace the basal insulin that should’ve have been infused<br />

if the pump were not disconnected. A bolus corresponding to 50% of the basal<br />

rate must be administered during the disconnection period.<br />

Do the following to determine the amount of insulin to be administered<br />

as a bolus in place of baseline:<br />

decide how long you will disconnect the pump <strong>for</strong> (max 2 hours)<br />

check the planned basal insulin rate during the disconnection period<br />

calculate a 50% basal insulin rate <strong>for</strong> the period of disconnection.<br />

EXAMPLE: you decide to disconnect the pump <strong>for</strong> 2 hours. The baseline<br />

planned in those 2 hours of disconnection is 0.6 U/h, during which the pump<br />

will infuse 1.2 U of insulin in 2 hours (i.e. 0.6 U in the first hour and 0.6 U in<br />

the second hour). You have to calculate 50% of the total of planned basal<br />

insulin <strong>for</strong> the 2 hours the pump is disconnected (i.e. half the baseline of 2<br />

hours).<br />

The bolus to be administered <strong>with</strong> the pump, be<strong>for</strong>e disconnection, is<br />

there<strong>for</strong>e equal to 0.6 U.<br />

In order to disconnect the pump <strong>for</strong> more than 1 hour (maximum 2 hours):<br />

check your blood glucose<br />

administer a bolus of insulin equal to 50% of the planned quantity of basal insulin<br />

in the disconnection period<br />

disconnect the catheter from the cannula<br />

protect the cannula and catheter extremities <strong>with</strong> their specific cap<br />

keep the pump operational (do not suspend infusion) <strong>with</strong> the planned basal rate<br />

to avoid interrupting insulin flow (thereby reducing the risk <strong>for</strong> occlusion).<br />

at the end of the disconnection period, check your blood glucose and reconnect the<br />

catheter to the cannula<br />

if necessary, correct an eventual high blood glucose <strong>with</strong> a bolus of insulin, applying<br />

the insulin sensitivity factor (also called correction factor).<br />

( 81<br />

Caution. After a meal or correction bolus there will be a substantial amount of<br />

available insulin in your blood, even if you disconnect the pump. In this case, your body<br />

will hardly be lacking insulin <strong>for</strong> the following 3-4 hours after the bolus has been<br />

administered.


Insulin pumps<br />

Insulin boluses<br />

It is often said that the pump gives freedom to the person who uses it. However, this<br />

“gift” comes at a price. In fact, the pump allows a more precise bolus insulin administration<br />

(<strong>for</strong> meals and high blood glucose). It is there<strong>for</strong>e necessary to be able to properly<br />

assess the required insulin dose – this requires precise calculations.<br />

The correction bolus<br />

The pump makes it very easy to administer correction boluses: the amount of insulin<br />

needed to bring blood glucose back to target range. To calculate the amount of required<br />

insulin, first calculate the difference between your current high blood glucose and<br />

your desired target. Divide this difference by the sensitivity or correction factor. For<br />

example, if the factor is 20, divide the difference between the current high blood glucose<br />

(<strong>for</strong> ex. 240 mg/dL) and desired target glucose( 120 mg/dL) by 20 (240-120=120<br />

→ 120/20=6). The result – 6 – is the number of units to be administered as correction<br />

bolus (which may be added to a meal bolus if you plan to eat). Remember that your<br />

insulin sensitivity may increase during physical activity and this calculation may thus<br />

overestimate your correction bolus.<br />

82 )<br />

Insulin sensitivity or correction factor<br />

Each person has an individual insulin sensitivity factor: to calculate it you must your<br />

average daily insulin requirement (the sum of basal and bolus units). Then divide the<br />

constant 1800 by the number of units representing your daily insulin requirement. For<br />

example, if your total daily insulin requirement is 90, 1800/90 is 20, which is the correction<br />

factor. There<strong>for</strong>e, in case of hyperglycaemia, each unit of insulin lowers the<br />

blood glucose level by 20 mg/dL.<br />

The correction factor is also useful in cases where the blood glucose be<strong>for</strong>e meals<br />

is less than the target value: <strong>for</strong> example, 70 instead of 90 mg/dL. In this case, subtract<br />

from the “food” bolus as many units as needed to bring the blood glucose level<br />

to the target value. In this case, given that 90-70 is equal to 20 and that the correction<br />

factor is 20, just decrease the insulin bolus by 1 unit to reduce the risk of hypoglycemia<br />

after the meal.<br />

The ‘food bolus’<br />

The insulin standard bolus administered using a pump is similar to that administered<br />

<strong>with</strong> an injection of rapid-acting insulin analog (e.g. Novorapid, Apidra, Humalog).<br />

The bolus is also referred to as a wave (standard, square or dual wave bolus), according<br />

to how the bolus is delivered by the pump. An insulin bolus should always be administered<br />

be<strong>for</strong>e eating. This is because ultrafast insulin takes about 15 minutes to<br />

start its effect.


Insulin pumps<br />

If you are not sure of the amount of carbohydrates that you will consume during<br />

a meal, you should administer a bolus be<strong>for</strong>e the meal anyway (calculate a bolus that<br />

covers the minimum amount of carbohydrates you are sure to consume). Then complete<br />

the meal bolus <strong>with</strong> the insulin required <strong>for</strong> the rest of the carbohydrates you have<br />

eaten and have not considered in the initial bolus. However. this tyope of conduct<br />

must be an exception, not the rule.<br />

How to calculate the “meal bolus”<br />

The amount of insulin required at meals depends on the amount of carbohydrates in<br />

the meal. At our Centre, all those who wish to start using a pump must follow an educational<br />

process that teaches them how to assess the amount of carbohydrates in a<br />

meal (or snack or drink) <strong>with</strong> sufficient accuracy.<br />

This technique, called carbohydrate counting or CHO counting, will be described<br />

in greater detail in another chapter, since it is not specific to insulin pump therapy.<br />

Once you have defined the amount of carbohydrates in a meal (in grams), in order<br />

to define the dose of insulin required you need to use a dividing factor known as<br />

the carbohydrate/insulin ratio. This ratio, initially determined by the team, is not constant:<br />

it may vary during the day and continues to change according to growth and<br />

pubertal development and must be continually verified by checking pre- and postprandial<br />

glucose values.<br />

The carbohydrate/insulin ratio is expressed as the amount of carbohydrates in<br />

grams that are metabolized by a single unit of rapid acting insulin. For example, a<br />

15/1 ratio means that 15 g of carbohydrates are metabolized by one unit of rapid acting<br />

insulin.<br />

EXAMPLE: a person <strong>with</strong> a carbohydrate/insulin ratio of 15 plans to eat 75<br />

grams of carbohydrates. 75 divided by 15 = 5. There<strong>for</strong>e, the meal bolus will<br />

be of 5U.<br />

Using the pump, you can set a maximum dose of insulin to administer as a bolus.<br />

In this way, you may prevent from administering an excessive insulin bolus by mistake.<br />

( 83


Insulin pumps<br />

Special boluses<br />

Using a pump, the amount of insulin required can be infused in the <strong>for</strong>m of a bolus<br />

<strong>with</strong> different distribution characteristics.<br />

Standard bolus: administers the required insulin as you would <strong>with</strong> a pen or syringe.<br />

Square wave bolus: distributes the amount of insulin required over the course of several<br />

hours, at a constant rate (you can imagine it as a very big basal rate).<br />

Dual wave bolus (or combined bolus): administers a portion of the bolus as a standard<br />

bolus and a portion like a square wave bolus.<br />

Dual-wave (Combined) bolus<br />

Use a dual wave bolus when sugars consumed during a meal are absorbed slowly. This<br />

may the case in meals that are rich in fiber, fat and protein (the nutrients reduce the<br />

absorption time of carbohydrates). Blood sugar levels are there<strong>for</strong>e likely to increase<br />

gradually over time, even when the standard bolus has finished its activity. For example,<br />

the intake of salad or spinach after a plate of pasta slows the absorption of carbohydrates.<br />

Pizza also determines a slower absorption of carbohydrates.<br />

Using a dual wave bolus, you can:<br />

Cope <strong>with</strong> an immediate need <strong>for</strong> insulin in order to limit an increase in blood glucose<br />

after meals (standard bolus)<br />

Distribute the insulin over following hours, in order to control the progressive increase<br />

of blood glucose related to the slower absorption of carbohydrates (square wave<br />

bolus).<br />

84 )<br />

In order to program the dual wave bolus, the pump asks:<br />

The overall amount of insulin to administer<br />

The percentage (or units) of insulin to be administered as a standard bolus and the<br />

percentage (or units) of insulin to be administered as a square wave bolus<br />

The duration of the square wave bolus.<br />

EXAMPLE: you eat a pizza and drink a can of a sugared beverage: the overall<br />

amount of carbohydrates consumed is 150 g. If the carbohydrate/insulin<br />

ratio is 15, divide the total carbohydrates (150) by 15.<br />

There<strong>for</strong>e, 150 divide by 15 = 10 U of insulin. You can decide to administer<br />

40% of the required bolus immediately in the <strong>for</strong>m of a standard bolus and<br />

60% in the <strong>for</strong>m of a square wave bolus over the course of 3-6 hours. The<br />

pump will administer 4 U in the <strong>for</strong>m of a standard bolus and 6 U in the <strong>for</strong>m<br />

of a square wave bolus over the following 3-6 hours, <strong>with</strong> a basal rate of 2<br />

U/hour.


Insulin pumps<br />

Square wave bolus<br />

A square-wave bolus is used when a meal lasts a longer than usual, such as a wedding<br />

reception. A square wave bolus is sort of like administering a very substantial temporary<br />

basal rate. Alternatively, in these situations you can administer a series of small<br />

boluses, based on the amount of carbohydrates consumed, although there might be<br />

an increased risk of overlapping boluses and there<strong>for</strong>e low blood glucose.<br />

In order to program the square wave bolus, the pump will ask:<br />

The overall amount of insulin to administer<br />

How long the administration of the dual wave bolus needs to last<br />

EXAMPLE: at a wedding reception, a person <strong>with</strong> a carbohydrate/insulin<br />

ratio of 12 plans to consume about 240 g of carbohydrates.<br />

1. The total amount of consumed carbohydrates is divided by the<br />

carbohydrate/insulin ratio: 240 divided by 12 = 20. 20 U of insulin will be<br />

required in order to “cover” the wedding meal.<br />

2. The meal and the subsequent period of digestion may approximately<br />

5 hours. The person decides to administer a square wave bolus over<br />

a period of 5 hours. An equivalent basal rate of 4 U/hour will be<br />

administered over a period of 5 hours.<br />

Caution. When using a pump it is easy to <strong>for</strong>get to administer the meal bolus. If you<br />

<strong>for</strong>get, even only a few times, your HbA1c may increase significantly. However, pump<br />

alerts can be set at specific times as a reminder.<br />

The bolus calculator<br />

The pump is able to suggest how many units of insulin are required <strong>for</strong> a bolus (<strong>for</strong> a<br />

correction and/or meal. This function is called the bolus calculator.<br />

( 85<br />

To use this feature, you must set the pump parameters to customize the calculation:<br />

The glycaemic target, i.e. the blood glucose level which you aim <strong>for</strong> in a certain time<br />

interval<br />

The insulin sensitivity factor<br />

The carbohydrate/insulin ratio in the different time intervals of the day<br />

The bolus activity duration (e.g. 3-4 hours).<br />

Once these parameters are set, every time you want to use this function you need to<br />

enter:<br />

The blood glucose measured at that time<br />

The amount of carbohydrates that you plan to consume


Insulin pumps<br />

Upon inserting these parameters, the pump calculates how much insulin to administer,<br />

depending on:<br />

The starting blood glucose level<br />

The glycaemic target<br />

The amount of carbohydrates consumed<br />

The amount of active insulin from a previous bolus (it subtracts the amount of active<br />

insulin that may have been administered earlier from the bolus that is being calculated).<br />

All of these variables can be calculated manually, but the pump helps to make<br />

calculations faster and more accurately as it also considers “insulin on board” (insulin<br />

that is still active from a previously administered bolus).<br />

For example, let us examine a person who has set the following parameters<br />

in his bolus calculator:<br />

Glucose target: 100 mg/dL<br />

Insulin sensitivity factor: 30 (1 U of insulin lowers the blood sugar level by 30 mg/dL)<br />

Carbohydrate/insulin ratio: 16 (1U of insulin “covers” 16 g of carbohydrates)<br />

Bolus Duration: 5 hours (the calculator will consider that the bolus will last 5 hours)<br />

86 )<br />

At 16.00, the individual decides to eat a ham sandwich.<br />

1. The persons blood glucose is 190 mg/dL. The glucose target <strong>for</strong> this interval of<br />

time is 100 mg/dL. There<strong>for</strong>e, the blood glucose is 90 mg/dL higher than target<br />

2. After applying the sensitivity factor, the result is that a 3 U need to be<br />

administered to correct the current blood glucose (90 mg/dL divided by 30 = 3 U)<br />

3. The person estimates that the sandwich contains 40 g of CHO. Considering a<br />

carbohydrate/insulin ratio of 16, this means that 2.5 U are required to “cover” it<br />

(40 g of carbohydrates divided by 16 = 2.5 U).<br />

4. At 4 p.m., however, part of the insulin used to cover lunch is still in circulation.<br />

The calculator ‘remembers’ that a 10 U bolus was administered at 1 p-m- and<br />

concludes that 4 U are still active at 4 p.m. In fact, after 3 hours, 40% of the<br />

bolus administered still needs to act.<br />

In conclusion, the bolus calculator adds the 2.5 U necessary <strong>for</strong> the sandwich to<br />

the 3 U necessary to correct the hyperglycaemia, but subtracts the 4 units still in<br />

circulation from the total (5.5 U) and there<strong>for</strong>e recommends a 1.5 U bolus.<br />

The bolus calculator calculates all the required variables. You only need to enter<br />

the measured blood glucose and the amount of carbohydrates.


Insulin pumps<br />

How to correct hyperglycaemia<br />

When blood glucose is above 250 mg/dL, it is necessary to: check whether the<br />

pump is operating correctly (reservoir, catheter and infusion site), verify previous commands<br />

in the pumps memory (boluses, basal, etc.) and measure blood ketones (positive<br />

if > 0.6 mmol/L) or ketonuria.<br />

Blood sugar > 250 mg/dL<br />

Check infusion set and previous boluses<br />

NO KETONES<br />

Pump-administered<br />

correction bolus<br />

Check both blood sugar and<br />

ketones one hour later<br />

KEtonEs<br />

If blood sugar is not reduced<br />

and there ar ketones<br />

If blood sugar is not reduced<br />

and there are no ketones<br />

Administer a correction bolus <strong>with</strong> a pen,<br />

supplemented by 50%<br />

Change infusion set<br />

Keep pump connected <strong>with</strong> relevant basal rate<br />

Check both blood sugar and ketones one hour<br />

later<br />

Drink a lot<br />

If blood sugar is not reduced<br />

and/or ketones are not<br />

reduced<br />

Contact your Diabetologist<br />

o go to nearest emergency<br />

unit<br />

Administer a correction<br />

bolus <strong>with</strong> a pen<br />

Change infusion set<br />

Check both blood sugar<br />

and ketones one hour later<br />

( 87


Insulin pumps<br />

If blood ketones are positive (>0.6 mmol/L):<br />

Use a syringe or pen to administer a bolus of rapid acting insulin, increasing the calculated<br />

bolus by 50%<br />

Replace the infusion set<br />

Keep the pump operational at the required basal rate<br />

Drink plenty of water and check blood glucose and ketones after 1-2 hours.<br />

If blood glucose has not decreased and the ketones are increasing, contact a <strong>diabetes</strong><br />

specialist or go to the nearest emergency department<br />

If blood glucose is decreasing and the ketones are negative or decreasing, measure<br />

blood glucose every 1-2 hours until it returns to normal.<br />

How to correct hypoglycaemia<br />

The risk of hypoglycaemia is statistically lower in <strong>people</strong> who properly use an insulin<br />

pump. The correction of hypoglycaemia in pump users follows the same principles <strong>for</strong><br />

those who use a syringe or a pen. Whenever you feel like or suspect that your blood<br />

glucose is low, the first thing to have to do is measure your blood glucose. A value<br />

below 70 mg/dL is considered low (hypoglycemia).<br />

Take 15 g of simple carbohydrates. 15 g may be too much <strong>for</strong> some children. To<br />

calculate the estimated correct amount, multiply your weight in kilograms by 0.3 to<br />

obtain the amount of grams of simple carbs.<br />

88 )<br />

After 15 minutes, check your blood glucose again:<br />

If blood glucose is below 100 mg/dL, an additional dose of 15 g of simple carbs is<br />

necessary<br />

If your blood glucose is above 100 mg/dL, your low blood glucose has been properly<br />

corrected.<br />

15 g of simple carbs are contained in:<br />

½ can sugared drink<br />

½ fruit juice<br />

1 fruit juice <strong>with</strong> no added sugar<br />

3 candies (<strong>with</strong> sugar)<br />

2-3 sachets of sugar<br />

1 apple


Insulin pumps<br />

Never eat snacks or pastries (snacks, chocolate, cake, etc.) to correct hypoglycaemia,<br />

they determine a much slower rise in blood glucose and usually contain<br />

more carbs than necessary thereby increasing blood glucose excessively.<br />

If hypoglycaemia reoccurs, it is advisable to take simple carbs as described be<strong>for</strong>e<br />

and reduce the basal insulin rate by setting a temporary basal rate reduced by 50%<br />

until the next meal in order to reduce the likelihood of new hypoglycemic episodes.<br />

Caution<br />

15 g of simple carbs may not be sufficient to correct hypoglycaemia which occurs<br />

during physical activity.<br />

15 g of simple carbs may not be sufficient to correct hypoglycaemia after an<br />

excessive insulin bolus.<br />

If you correct your blood glucose in the wrong way, you risk<br />

increasing it excessively.<br />

Physical exercise<br />

It is essential to adjust the insulin dose and carbohydrate intake to reduce the risk of<br />

hypoglycaemia or hyperglycaemia during physical exercise.<br />

To identify how much insulin acts during a sporting activity, you must consider:<br />

The basal insulin rate<br />

How much insulin is still active from a previous bolus<br />

The amount of insulin that is still active from a previous bolus may be excessive<br />

(even if the pump has been disconnected) and increases the risk of hypoglycaemia.<br />

When exercise is over, the body needs to replenish its stocks of glucose, extracting<br />

it from the bloodstream. It also increases insulin sensitivity, meaning that the<br />

same dose of insulin has a greater metabolic effect. There<strong>for</strong>e, the risk of hypoglycaemia<br />

also increases after physical exercise.<br />

( 89<br />

Be<strong>for</strong>e starting a planned physical activity you must:<br />

1. Evaluate whether to disconnect the pump and, if so, <strong>for</strong> how long.<br />

If you disconnect the pump:<br />

For less than 1 hour, check your blood glucose and disconnect the pump;<br />

For 1 to 2 hours: check your blood glucose and administer an insulin bolus equal<br />

to 50% of the basal rate required during the disconnection period (see ‘Temporary<br />

disconnection’).


Insulin pumps<br />

If you do not disconnect the pump:<br />

To avoid hypoglycaemia during physical exercise, decrease the basal rate <strong>for</strong> that<br />

moment of day (or use a reduced temporary basal rate <strong>for</strong> the necessary amount<br />

of time). This is useful during prolonged exercising, such as hiking or biking.<br />

2. Carry your blood glucose meter, insulin and the foods necessary to<br />

correct low blood glucose.<br />

3. Check your blood glucose be<strong>for</strong>e and regularly thereafter.<br />

Blood glucose between 120 and 180 mg/dL<br />

Consume 15-20 g of carbohydrates. Since you “burn” glucose during physical<br />

exercise, you need to “refuel” in order to have a sufficient amount of glucose.<br />

Blood glucose > 250 mg/dL <strong>with</strong>out ketones<br />

After having administered a correction dose of insulin, you may carry out<br />

your planned physical activity. Administer a bolus of insulin (see ‘How to correct<br />

hypoglycaemia’, p. 87), but do so <strong>with</strong> extreme care, since your blood<br />

sugar will tend to decrease more than usual (physical activity increases insulin<br />

sensitivity).<br />

Blood glucose > 250 mg/dL <strong>with</strong> ketones<br />

Avoid physical activity. Administer a bolus of insulin as explained previously<br />

(see ‘How to correct hyperglycaemia’, page 86), When blood glucose and ketones<br />

are both elevated, there is an increased risk of ketoacidosis.<br />

90 )<br />

Hypoglycaemia<br />

Avoid physical activity. In this case, per<strong>for</strong>m a correction <strong>with</strong> 15g (or 30g in<br />

case you plan to start your physical activity afterwards) of simple carbohydrates,<br />

until the blood glucose exceeds 100 mg/dL (see ‘How to correct hypoglycaemia’,<br />

page 87).<br />

After physical exercise:<br />

If the pump has been disconnected: re-connect it (<strong>with</strong>in 2 hours), check your<br />

blood glucose and correct your low or high blood glucose as necessary.<br />

For other precautions, see the section dedicated to physical exercise.


Insulin pumps<br />

In case of illness<br />

During intermittent illnesses (ie. the flu), insulin may not work as usual (febrile conditions<br />

increase the body’s resistance to insulin’s effect). This usually means that more<br />

insulin is needed to obtain the same metabolic effect.<br />

Hyperglycaemia<br />

If you administer a standard dose of insulin, blood glucose tends to rise more than<br />

usual. There<strong>for</strong>e, high blood glucose may appear often during the a sick day.<br />

What needs to be done?<br />

Check your blood glucose often. IIf your blood glucose remains constantly high, increase<br />

your temporary basal rate and/or administer extra boluses of insulin.<br />

Measure blood ketones<br />

If you detect high blood glucose and ketones, immediately administer an extra dose<br />

of insulin as previously explained (see ‘How to correct hyperglycaemia’, page 86).<br />

If hyperglycaemia persists and/or you start experiencing abdominal pain and/or<br />

drink and urinate often, you should contact the <strong>diabetes</strong> healthcare team or go to<br />

the nearest emergency department – you may be undergoing diabetic ketoacidosis.<br />

Hypoglyceamia<br />

In case of vomiting or diarrhea (ie. Gastroenteritis), blood sugar levels tend to fall. This<br />

could lead to frequent lo blood glucose values. What needs to be done?<br />

Check your blood glucose often.<br />

In case of hypoglycaemia, take small sips of sugared liquids.<br />

Reduce all doses of insulin, especially boluses. Even when fasting <strong>for</strong> several hours,<br />

never completely suspend your basal insulin (see ‘The temporary basal rate’, page<br />

78), in order to prevent ketoacidosis.<br />

If you are unable to correct low blood glucose orally, go to the nearest emergency<br />

department.<br />

In case of intermittent diseases, a person <strong>with</strong> <strong>diabetes</strong> may take all the necessary<br />

medications (compatibly <strong>with</strong> ones allergies). However, there are drugs that increase<br />

blood glucose levels, such as cortisones. The use of these drugs requires an<br />

adjustment of insulin doses to maintain glucose control.<br />

( 91


Insulin pumps<br />

Transition to multi-injection therapy<br />

In case of need, you can always interrupt pump therapy and temporarily transition to<br />

multiple injection therapy using pens or syringes.<br />

To switch to a multiple injection regimen, you must:<br />

Calculate the total daily (24h) basal insulin dose<br />

Replace the units of basal insulin <strong>with</strong> a long-acting insulin analog. For example<br />

a baseline of 0.2 U/h is equivalent to a total daily dose of 4.8U, which may be<br />

rounded up to 5 U of long-acting insulin.<br />

Administer the same amount of units of rapid-acting insulin analog <strong>for</strong> meals (units<br />

of pump bolus = units of rapid-acting insulin analog injection)<br />

It is important to remember:<br />

That the injection of long-acting insulin must always be carried out at the same time<br />

To interrupt the insulin pump therapy 1-2 hours after the long-acting insulin has been<br />

administered.<br />

That the risk of overlapping insulin doses adminisetered by pump and injection if<br />

the transition is not planned correctly.<br />

In the first days after transition, you should check your blood glucose more often<br />

as insulin doses might have to be adusted. A few days may be necessary be<strong>for</strong>e<br />

the most correct multiple injection doses can be found. If necessary, contact your <strong>diabetes</strong><br />

healethcare team.<br />

92 )


Insulin pumps<br />

Continuous glucose monitoring (CGM)<br />

It is possible to combine insulin pump therapy <strong>with</strong> continuous glucose monitoring<br />

(CGM). With CGM, one can better evaluate glucose trends in “real-time” and implement<br />

more precise insulin adjustments.<br />

Continuous glucose monitoring is per<strong>for</strong>med by a subcutaneous sensor which<br />

remains in place <strong>for</strong> 3-7 days (up to 14 days in some cases). The sensor measures<br />

the concentration of (interstitial) glucose in the subcutaneous tissue, not in the blood.<br />

The interstitial glucose values are comparable to those in the blood in the majority<br />

of cases.<br />

The CGM system needs to be calibrated <strong>with</strong> blood glucose determination (approximately<br />

1 blood glucose value every 12 hours). Continuous glucose monitoring<br />

does not replace standard blood glucose monitoring, but provides additional in<strong>for</strong>mation.<br />

Be<strong>for</strong>e making therapeutic decisions, it is always better to confirm that data from<br />

CGM <strong>with</strong> a blood glucose measurement.<br />

It is important to remember that CGM reading may be delayed (about 15-20 minutes)<br />

compared to capillary blood glucose. This delay increases when blood glucose<br />

is changing quickly.<br />

one arrow up <br />

check blood sugar<br />

two arrows up <br />

check blood sugar<br />

above 150<br />

mg/dL<br />

under 150<br />

mg/dL<br />

insulin bolus<br />

<strong>with</strong> IFS +10%<br />

check blood sugar<br />

30 minutes later<br />

insulin bolus<br />

<strong>with</strong> IFS +20%<br />

( 93<br />

two arrows down ‣‣<br />

check blood sugar<br />

one arrow down ‣<br />

check blood sugar<br />

under 150<br />

mg/dL<br />

above 150-200<br />

mg/dL<br />

under 100<br />

mg/dL<br />

above 100-150<br />

mg/dL<br />

15-30 g of<br />

fast-acting sugar<br />

check blood sugar<br />

30 minutes later<br />

15 g of<br />

fast-acting sugar<br />

check blood sugar<br />

30 minutes later


Insulin pumps<br />

The CGM a better understanding of glucose trends by showing a number of arrows<br />

<strong>with</strong> different inclination which represent different speeds of glucose variation.<br />

2 arrows indicate that your blood sugar level changes at a rate that is greater than<br />

2 mg/dL/min;<br />

1 arrow indicates that the glucose changes at a rate that is greater between 1-2<br />

mg/dL/min. For example, if your glucose trend is increasing, you may consider administering<br />

a small insulin to prevent hyperglycaemia.<br />

When you practice sports, eat or have just administered a bolus of insulin, blood<br />

glucose variations are more likely and more rapid. The sensor can show trend arrows<br />

that need correct interpretation. For example, if you have just taken a correction<br />

bolus <strong>for</strong> hyperglycaemia and the sensor shows two upwards pointing arrows, do not<br />

administer a second bolus of insulin, but wait until the first correction bolus has taken<br />

effect (1-2 hours). The arrows will probably soon disappear or even show a decreasing<br />

glucose trend. Remember that the sensor reads changes <strong>with</strong> a delay (lag-time)<br />

<strong>with</strong> respect to capillary blood glucose. Sensor accuracy is maintained if it is calibrated<br />

<strong>with</strong> stable blood glucose values. It is there<strong>for</strong>e important to avoid calibrating the<br />

sensor after meals or during physical activities.<br />

The algorithm that follows is an example and should be personalized and discussed<br />

<strong>with</strong> your <strong>diabetes</strong> healthcare team.<br />

Changes in insulin therapy<br />

94 )<br />

Diabetes self-management is the cornerstone of multiple injection therapy and it is<br />

important that children and adolescents <strong>with</strong> <strong>diabetes</strong> actively manage their disease<br />

as soon as possible. The hardest part of this independence-acquiring process is gaining<br />

the ability to estimate insulin doses. In fact, the amount of insulin that each child/<br />

adolescent needs is a variable that must be continually adjusted according to:<br />

Growth in height and weight<br />

Habits and lifestyle<br />

Physical activity<br />

Any intermittent illnesses<br />

Menstrual cycle<br />

To properly adjust doses, you must be able to correctly interpret blood glucose<br />

and ketones, and understand the mechanism of action of the insulin types that are<br />

being used.


Facing or clashing<br />

<strong>with</strong> <strong>diabetes</strong>


Facing or clashing <strong>with</strong> <strong>diabetes</strong><br />

96 )<br />

If you are a child/adolescent <strong>with</strong> <strong>diabetes</strong>, you will probably think of your daily<br />

<strong>diabetes</strong> management <strong>with</strong> a sense of boredom or anger. For example, you may feel<br />

that your insulin injections are an injustice and that they make you feel different from<br />

your peers or family members. You might ask yourself “Why do I have to take insulin<br />

and my brother doesn’t?” or “Why do I have to drink Coke Zero instead of normal<br />

Coke, like my friends do?”.<br />

If you’re a teenager <strong>with</strong> <strong>diabetes</strong>, it is crucial to maintain many friendships,<br />

commitments, interests and hobbies. However, some typical characteristics of this age<br />

can contribute to making your relationship <strong>with</strong> <strong>diabetes</strong> difficult. During adolescence,<br />

changes in your body and your mind may easily foster insecurity. This is why some<br />

children/adolescents of the same age see <strong>diabetes</strong> as a more serious and disturbing<br />

condition than it really is. Your natural growing need <strong>for</strong> emancipation and independence,<br />

can make you less accepting of the advice and monitoring supplied by family<br />

members and healthcare team.<br />

The typical uncertainties of adolescent age (“How am I seen, what do others<br />

think of me?”) may lead you to imagine that others may have negative connotations<br />

towards <strong>diabetes</strong> and its treatment which may then reflect on you. Some react by<br />

trying to deny the existence of the problem (<strong>diabetes</strong>), thus neglecting daily <strong>diabetes</strong><br />

self-management.<br />

The duration of these negative reactions may vary. A frank conversation <strong>with</strong> a<br />

family member or friend, a discussion <strong>with</strong> peers <strong>with</strong> <strong>diabetes</strong>, or a dialogue <strong>with</strong><br />

your healthcare team, may help understand that you may have neglected <strong>diabetes</strong> because<br />

of a desire to break the rules, or to get back at your parents. These confrontations<br />

may help you understand that neglecting <strong>diabetes</strong> management may be correlated<br />

to an unfounded fear that peers might look down on you upon discovering<br />

your therapeutic needs. Refusing to manage <strong>diabetes</strong>, may also reflect pre-existing discom<strong>for</strong>ts<br />

or difficulties in other areas of your life (schoo, family, relationships).<br />

Once you have understood the real reasons behind these difficulties, you can<br />

constructively direct your ef<strong>for</strong>ts towards <strong>diabetes</strong> control, ensuring your well-being in<br />

the present and future, and increasing your self-esteem. With the limitations and obstacles<br />

that <strong>diabetes</strong> may bring <strong>for</strong>th, a teenager has the opportunity to find strength,<br />

resource, and acquire special skills that may help in dealing <strong>with</strong> other difficult situations<br />

in life. In fact, you may become better prepared to deal <strong>with</strong> the future that, as<br />

<strong>with</strong> all adolescents (<strong>with</strong> or <strong>with</strong>out <strong>diabetes</strong>), may provide gratification and satisfaction,<br />

as well as burdens and difficulties.<br />

A person <strong>with</strong> <strong>diabetes</strong> should always remember to make healthier lifestyle<br />

choices than those of a person <strong>with</strong>out <strong>diabetes</strong>!


Facing or clashing <strong>with</strong> <strong>diabetes</strong><br />

In addition to all the actions necessary to achieving glucose targets, it is essential<br />

that you follow a healthy lifestyle:<br />

Eat as healthy as possible<br />

Maintain an adequate body mass index<br />

Exercise regularly physical activity is essential to keep in shape<br />

Do not smoke: smoking is the best way to ruin all your other ef<strong>for</strong>ts.<br />

( 97


Particular situations


Particular situations<br />

Intermittent illnesses<br />

Normal infectious diseases caused by viruses and bacteria can alter glucose control.<br />

Childhood rashes (measles, rubella, chicken pox, etc.), infections of the upper respiratory<br />

tract (tonsillitis, otitis), gastroenteritis and influenza are especially frequent during<br />

childhood.<br />

During an infectious disease, blood glucose tends to increase as insulin, in these<br />

situations, fails to act effectively. The greatest risk <strong>for</strong> a child/adolescent <strong>with</strong> <strong>diabetes</strong><br />

during an infectious disease is the development of ketoacidosis. It takes about 24<br />

hours to develop and once started it tends to progressively worsen if adequate measures<br />

are not taken.<br />

What needs to be done to prevent ketoacidosis<br />

Frequent evaluations of blood glucose, blood/urine ketones are necessary in order to<br />

correctly adjust insulin doses.<br />

Maintain an adequate supple of carbohydrates. If you are unable to ingest solid foods,<br />

you need to drink sugared beverages (lemon tea, etc.). When suffering from<br />

persistent vomiting and hypoglycaemia, take small and frequent sips of sugared beverages.<br />

In case of hypoglycaemia and an inability to ingest food (such as in cases of gastroenteritis),<br />

small doses of glucagon may be administered subcutaneously using an<br />

insulin syringe at doses of 1 unit <strong>for</strong> each year of age, from a minimum of 2U to a<br />

maximum of 15 U. The dose can be repeated 1½-2 hours later.<br />

If blood sugar levels are consistently high, increase rapid-acting insulin doses, as it<br />

is easier to manage when food consumption is irregular.<br />

If blood sugar levels are consistently high (above 300 mg/dL) and ketones are persistently<br />

present, take an extra dose of rapid-acting insulin using your insulin sensitivity<br />

factor and increase the dose by 50% percent (<strong>for</strong> example if your standard<br />

correction dose <strong>for</strong> a specific hyperglycemia should be 6U, administer 9 units of insulin).<br />

Your blood glucose and ketones should progressively decrease.<br />

If you are unable resolve the situation, call your <strong>diabetes</strong> healthcare team or go to<br />

the nearest emergency department.<br />

( 99<br />

Never completely suspend insulin, even if you are consuming<br />

little or no food.


Particular situations<br />

Useful tips<br />

If unresolved, ketoacidosis requires emergency admission to hospital <strong>for</strong><br />

the infusion of fluids and intravenous insulin.<br />

In case of fever, you can take common fever medications. As far as<br />

antibiotics are concerned, it is best to consult your healthcare provider.<br />

A child <strong>with</strong> <strong>diabetes</strong> deals <strong>with</strong> common intermittent illnesses as all other<br />

children do, and does not have a weaker immune system.<br />

A child <strong>with</strong> <strong>diabetes</strong> can take all the necessary medications that a doctor may<br />

prescribe (compatibly <strong>with</strong> allergies). In some cases, insulin doses may need to be<br />

adjusted.<br />

Travel and holidays<br />

People <strong>with</strong> <strong>diabetes</strong> can travel anywhere <strong>for</strong> holiday or business reasons. Just be well<br />

organized and follow these tips:<br />

Be<strong>for</strong>e leaving<br />

Plan any vaccinations required <strong>for</strong> the country you will be visiting.<br />

What to pack:<br />

Syringes/pens and/or infusion<br />

Suitcase<br />

sets and related needles<br />

Test strips to determine blood glucose and ketones<br />

Lancets<br />

Glucagon<br />

Simple carbohydrates<br />

100 )<br />

It is always best to bring more material than the amount you plan to use during<br />

your stay. If you are traveling by air, do not put insulin in your cargo luggage: the<br />

low temperature of the cargo could freeze the insulin, altering its biochemical properties.<br />

Always keep insulin, glucagon, syringes or pens or infusion sets and related<br />

needles, glucometers, lancing devices, lancets and simple sugars in your hand luggage.<br />

Make sure to ask your doctor <strong>for</strong> a certificate stating your medical condition and<br />

your need to carry insulin and all necessary equipment <strong>for</strong> <strong>diabetes</strong> management during<br />

your travel (in English if you go abroad). We recommend that you apply <strong>for</strong> a travel<br />

insurance that covers medical and hospital care expenses in case of emergency.


Particular situations<br />

During a trip<br />

When on a ship, if you suffer from motion sickness, you can take common motion<br />

sickness medication. These medications do not alter glucose control. By plane, it is<br />

possible to ask the airline <strong>for</strong> a gluten free menu. By car, bus or train, it is advisable<br />

to carry an adequate amount of carbohydrates <strong>for</strong> the duration of the trip.<br />

Crossing time zones<br />

You might take flights abroad in countries <strong>with</strong> different time zones. In these cases,<br />

pay particular attention to your schedule and the insulin dose. For time differences of<br />

less than 3-4 hours, do not take additional doses of insulin, but upon arrival take the<br />

usual dose of insulin corresponding to local time. If the difference is greater than 3-4<br />

hours, take an extra dose of rapid-acting insulin equal to 10-15% of the total dose<br />

4-5 hours after the last administration; upon arrival, administer the usual dose of insulin<br />

corresponding to local time. It is always better to discuss the best option <strong>with</strong> your<br />

<strong>diabetes</strong> healthcare team be<strong>for</strong>e you leave. Always per<strong>for</strong>m an adequate number of<br />

blood glucose tests during the trip and first days of your stay as your glucose variability<br />

may increase due to the change in time zone.<br />

Dental treatment<br />

People <strong>with</strong> <strong>diabetes</strong> can undergo routine dental procedure <strong>with</strong>out the need <strong>for</strong> specific<br />

precautions. It is advisable to contact the anaesthesiologist in advance if general<br />

anaesthesia is required. Blood clotting and tissue healing is absolutely normal in a person<br />

<strong>with</strong> <strong>diabetes</strong> in good control.<br />

While tooth cavities is unaffected by glucose control, the onset of periodontitis<br />

(alveolar pyorrhea) may be influenced by consistently high blood glucose levels.<br />

Proper oral hygiene, brushing and flossing after every meal, is essential in avoiding<br />

frequent dental treatment.<br />

( 101


Particular situations<br />

Pregnancy<br />

A woman <strong>with</strong> type 1 <strong>diabetes</strong> can have a successful pregnancy, as long as the pregnancy<br />

is planned.<br />

As always, it is essential that the female of childbearing age <strong>with</strong> <strong>diabetes</strong> receieves<br />

proper education, regarding the planning of pregnancy and the need <strong>for</strong> optimal<br />

metabolic control especially be<strong>for</strong>e and during pregnancy. This reduces the<br />

risk <strong>for</strong> fetal complications related to poorly controlled <strong>diabetes</strong> (mal<strong>for</strong>mations, hypoglycaemia,<br />

macrosomia).<br />

Pregancy in the context of <strong>diabetes</strong> should be closely monitored ina a <strong>diabetes</strong>specialized<br />

center throughout all its duration. It may often be necessary to increase<br />

insulin doses, even two or three fold, in order to maintain stable blood glucose levels<br />

and there<strong>for</strong>e an adequate HbA1c. Fetal growth should be evaluated by ultrasound<br />

at regular intervals and delivery should be planned as close as possible to the end of<br />

pregnancy. There is no need to resort to a Caesarean section unless medical or obstetric<br />

issues arise.<br />

Children of diabetic mothers <strong>with</strong> adequate glucose control still weigh slightly<br />

than average in spite of all ef<strong>for</strong>ts. However, <strong>with</strong> the exception of specific situations,<br />

there are usually no particular problems. The greatest risk <strong>for</strong> these children is the onset<br />

of hypoglycaemia, jaundice or hypocalcaemia in the first hours following birth.<br />

Normal breast-feeding recommendations apply to diabetic mothers as well. Breastfeeding<br />

usually requires an increased carbohydrate intake (about +50 g of carbohydrates<br />

per day) and an increased fluid intake. These measures do not normally affect<br />

insulin doses. It has been shown that breast-fed children may have a reduced risk<br />

of developing type 1 <strong>diabetes</strong>. Severe <strong>diabetes</strong> complications (advanced retinopathy<br />

and nephropathy) of <strong>diabetes</strong> can be a contraindication <strong>for</strong> pregnancy.<br />

102 )<br />

Planning pregnancy<br />

It is important <strong>for</strong> conception and pregnancy to progress in a context of optimal glucose<br />

control. Contraception ma also be suggested and be discussed <strong>with</strong> your <strong>diabetes</strong><br />

healthcare team.<br />

Natural methods of regulation and fertility control:<br />

> ovulation method: this is based on the observation of cervical mucus to determine<br />

the fertile period;<br />

> basal body temperature method: this is useful to recognize the end of the ovulatory<br />

Contracepti<br />

phase. Good levels of effecicacy are obtained in patients who are well motivated<br />

and have undergone adequate education.<br />

Barrier contraception (condoms or diaphragms): these are recommended,<br />

especially <strong>for</strong> <strong>young</strong>er <strong>people</strong>. They are also important <strong>for</strong> the prevention of sexually<br />

transmitted diseases.


Contraceptio<br />

Particular situations<br />

Intrauterine devices (spiral): these are not recommended, especially <strong>for</strong> <strong>young</strong><br />

methods<br />

women, due to possible side effects.<br />

Oral contraceptives (low-dose estroprogestins) provide a good safety profile,<br />

but may interfere <strong>with</strong> glucose control, resulting in increased insulin requirements<br />

and increased body weight. Periodic blood tests will be necessary, especially to serum<br />

lipids and coagulation. The same contraindications apply as <strong>for</strong> non-diabetic<br />

patients.<br />

Smoking<br />

Smoking is the leading cause of lung cancer, chronic bronchitis and pulmonary emphysema.<br />

It is also one of the primary risk factors <strong>for</strong> diseases of the heard (coronary artery<br />

disease), major vessels of the lower extremities (gangrene) and of the brain (strokes).<br />

In fact, smoking is the cause of a third of the deaths in middle-aged <strong>people</strong>.<br />

Why is smoking harmful? The chemicals in tobacco are responsible <strong>for</strong> lung diseases:<br />

tar restricts the flow of air into the lungs and carbon monoxide decreases the<br />

oxygenation of peripheral tissues. Nicotine in cigarettes causes addiction to smoking.<br />

Only adequate glucose control and a careful lifestyle will prevent microvascular<br />

and macrovascular complications: it is there<strong>for</strong>e necessary to avoid adding another<br />

risk factor.<br />

Studies involving complications clearly demonstrate that smoking is able to abolish<br />

the preventive effect of an adequate glucose control (which is often obtained <strong>with</strong><br />

great sacrifice).<br />

In terms of the risk of complications, it is as if smokers who have achieved and<br />

HbA1c of 7% (i.e. <strong>with</strong>in the target value) actually achieved a value of 8.5% due to<br />

the risk of complications induced by smoke.<br />

There<strong>for</strong>e:<br />

( 103<br />

1. Avoid smoking: once you start, it is very difficult to give up.<br />

2. If you are already a smoker:<br />

Pick a day to stop smoking: throw away all your cigarettes, matches and lighters<br />

on<br />

Fill your day <strong>with</strong> commitments, do sporting activities, but do not allow yourself<br />

to be bored<br />

Ask your doctor, family and friends to help you during this period


Particular situations<br />

3. There are many immediate benefits:<br />

You will feel much better both physically and mentally<br />

You will be able to taste food properly again<br />

You will improve your sense of smell<br />

You will no longer bother non-smokers.<br />

Do not smoke: you will live better and longer.<br />

Diabetes camps<br />

104 )<br />

Diabetes awareness and education are the starting point in the management of <strong>diabetes</strong>.<br />

Self-management education means providing children/adolescents <strong>with</strong> <strong>diabetes</strong><br />

and their parents <strong>with</strong> the necessary tools to deal confidently <strong>with</strong> the daily <strong>diabetes</strong>-related<br />

issues.<br />

During hospitalization, outpatient visits, and specific <strong>diabetes</strong>-update meetings,<br />

doctors, nurses and dieticians provide theoretical education and training regarding<br />

the practical aspect.<br />

Diabetes camps are a particularly interesting event <strong>for</strong> children/adolescents <strong>with</strong><br />

<strong>diabetes</strong>. In these camps, children/adolescents <strong>with</strong> <strong>diabetes</strong> go on a week trip <strong>with</strong><br />

their <strong>diabetes</strong> healthcare team (doctors, nurses, dieticians, psychologists). During this<br />

trip they are provided <strong>with</strong> daily educational and recreational activities which provide<br />

theoretical and practical <strong>diabetes</strong>-related in<strong>for</strong>mation which can be applied in<br />

everyday life. Camps are organized at holiday resorts that also offer the opportunity<br />

to practice sporting activities. Discussions <strong>with</strong> other peers <strong>with</strong> <strong>diabetes</strong> can<br />

provide useful insights and solutions to the daily obstacles that <strong>diabetes</strong> may<br />

provide.


Particular situations<br />

Recommended check-ups<br />

A routine outpatient visit should be per<strong>for</strong>med every 3-4 months, during which glycated<br />

hemoglobin or HbA1c is evaluated. HbA1c may be evaluated by taking venous<br />

blood or capillary blood samples (in the same way blood glucose is tested).<br />

Hemoglobin, which has the function of carrying oxygen, has a tendency to bind<br />

glucose slowly and irreversibly: there<strong>for</strong>e, if blood sugar levels are high <strong>for</strong> a long time,<br />

glucose binds <strong>with</strong> hemoglobin to <strong>for</strong>m glycosylated or glycated hemoglobin.<br />

Glycated hemoglobin provides in<strong>for</strong>mation regarding glucose control over the previous<br />

three months.<br />

Following an international convention and starting from January 2011, HbA1c<br />

will no longer be expressed as a %, but as mmol/mol.<br />

In the non-diabetic population, normal Hba1c values are 4-6% (24 to 42 mmol/<br />

mol).<br />

Children/adolescents <strong>with</strong> <strong>diabetes</strong> should try to achieve near-normal HbA1c –<br />

values below 7.5% (56 mmol/mol) are considered adequate. An American study has<br />

shown that maintaining an HbA1c below 7% (42 mmol/mol) may prevent a relevant<br />

proportion of diabetic complications. Elevated HbA1c’s mean that previous 3 months<br />

have been characterised by a releveant number of high glucose values.<br />

Currently, the evaluation of <strong>diabetes</strong>-selfmanagement also assesses the distribution<br />

of blood glucose values through the use of computer programs. In addition<br />

to average blood glucose level, blood glucose variability and exposure to hypo- and<br />

hyperglycaemia are also important. The percentage of values above 180 mg/dL and<br />

less than 80 mg/dL are evaluated – the goal is to achieve as high a number of blood<br />

glucose levels <strong>with</strong>in the target range. In addition, you can obtain other glucose variability<br />

indices to more accurately assess glucose control.<br />

Certain blood tests and examinations should be per<strong>for</strong>med annually. These include<br />

screening <strong>for</strong> thyroid and celiac disease, microalbuminuria, fundus oculi examination.<br />

After 10 years of <strong>diabetes</strong> duration or be<strong>for</strong>e the transition to an adult <strong>diabetes</strong><br />

outpatient clinic(at 18 years of age), it is good practice to undergo a complete screening<br />

<strong>for</strong> <strong>diabetes</strong> complications: microalbuminuria, electromyography (which analyses<br />

the functionality of the peripheral nervous system), re-evaluation of the situation in<br />

the retina (fundus oculi and, if necessary, retinal fluorescein angiography) and Doppler<br />

ultrasound of the carotid arteries.<br />

( 105


The future of<br />

<strong>people</strong> <strong>with</strong> <strong>diabetes</strong>


The future of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong><br />

Type 1 <strong>diabetes</strong> is an ancient illness, but we have only been able to treat it effectively<br />

since 1922, when insulin was discovered. Marvelous advances in <strong>diabetes</strong> treatment<br />

have been developed in these 90 years, particularly <strong>for</strong> what concerns technology.<br />

There is no doubt that <strong>with</strong> the development of self-management tools <strong>for</strong> home<br />

use, a significant improvement in the quality of life of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong> has been<br />

achieved – this has been made possible <strong>with</strong> the development of newer and more<br />

precise instruments such as blood glucose meters and continuous glucose monitors,<br />

as well as increasing continuous education <strong>for</strong> patients and parents regarding all<br />

aspects of <strong>diabetes</strong>.<br />

Let’s take a look at the future of <strong>diabetes</strong>!<br />

Prevention<br />

It has become clear <strong>for</strong> some time that type 1 <strong>diabetes</strong> arises when one or more<br />

“environmental” factors, called “triggers”, activate an autoimmune response that<br />

destroys ß-cells in genetically predisposed individuals. “Environmental” dose not only<br />

refer to factors that are strictly related to the environment (such as chemical pollution,<br />

etc.) but to anything <strong>with</strong> which the body may come into contact in the environment.<br />

Genetics. The fact that type 1 <strong>diabetes</strong> correlated to other autoimmune diseases<br />

(thyroiditis, celiac disease, certain <strong>for</strong>ms of allergy) suggests that in some individuals<br />

the immune system is less capable of distinguishing between external agents and the<br />

cells of one’s own body, and is there<strong>for</strong>e more inclined to develop autoimmune diseases.<br />

Preclinical phase. Despite an onset which may suggest a condition that has developed<br />

rapidly, we now know that what may seem the beginning of type 1 <strong>diabetes</strong> is<br />

actually the final stage of a long-lasting phenomenon which consists of two phases.<br />

In the first phase antibodies start to damage beta cells, while in the second phase<br />

beta cells are slowly destroyed. During this preclinical stage, we are able to identify<br />

those in whom this immune process is taking place by searching <strong>for</strong> autoantibodies.<br />

It is easier to identify a person at risk of type 1 <strong>diabetes</strong> mellitus in a family in which<br />

there has already been a case of <strong>diabetes</strong> mellitus, rather than someone in the general<br />

population. However, the presence of different antibodies (ICA, GAD, IA2, IAA,<br />

ZNT8) is not uncommon in the general population and in only a minority of cases do<br />

they determine ß-cell destruction.<br />

( 107


The future of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong><br />

In the second phase, well be<strong>for</strong>e the appearance of the typical symptoms of <strong>diabetes</strong><br />

onset, it is possible to detect abnormalities in rapid insulin secretion per per<strong>for</strong>ming<br />

an IVGTT (a test which evaluates the insulin response to a dose of glucose administered<br />

intravenously). Individuals <strong>with</strong> specific antibodies and altered IVGTT have<br />

more than a 90% chance of developing <strong>diabetes</strong>, particularly those <strong>with</strong> a high genetic<br />

predisposition.<br />

Unlike monogenic diseases in which there is a clear cause-effect relationship<br />

between gene and disease, in type 1 <strong>diabetes</strong> the relationship is indirect. There<strong>for</strong>e<br />

it does not seem useful to intervene on the genetic aspect of the disease since more<br />

than one gene is probably involved in the disease process.<br />

The search <strong>for</strong> the “trigger”. The most interesting aspect involves searching <strong>for</strong> environmental<br />

factors (or others) that may trigger an autoimmune response involving<br />

the development of autoreactive cells and antibodies directed against ß-cells. By identifying<br />

the cause, it would then be possible to avoid or delay the the onset or progression<br />

of the disease.<br />

Research protocols on this topic are being carried out throughout the world. There<br />

is a long list of substances currently undergoing trials <strong>with</strong> the aim of discovering<br />

whether or not they could act as “<strong>diabetes</strong> triggers”. Hopefully in the future there will<br />

be an “antidote” capable of preventing such an important disease.<br />

Tertiary prevention. Currently, greater results are possible in what is known as “tertiary<br />

prevention” – interventions aimed at maintaining residual secretion in newly diagnosed<br />

patients. A very interesting topic, especially <strong>for</strong> what concerns research centre,<br />

involves the study of regulatory cells and the future possibility of being able to<br />

modify these cells in order to avoid the need to resort to immunosuppression.<br />

108 )


The future of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong><br />

Transplants<br />

Transplants are considered a possible “treatment” <strong>for</strong> <strong>diabetes</strong>. A transplant is the transfer<br />

an organ, tissue or cells from a donor to the patient. There are several types of transplants<br />

which may be used in the treatment of <strong>diabetes</strong>.<br />

Pancreas transplantation<br />

Pancreas transplantation is a surgical procedure in which the whole organ is transplanted.<br />

It was the first technique to be tested in order to improve glucose control<br />

and stop the progression or prevent the onset of degenerative complications related<br />

to <strong>diabetes</strong>.<br />

Pancreas transplantation eliminates the need <strong>for</strong> daily insulin administrations in<br />

the majority of patients. However, this type of surgery is demanding, it is often difficult<br />

to find a compatible donor and above all, it requires the administration of immunosuppressive<br />

therapy to prevent rejection of the transplanted organ by the immune<br />

system. Immunosuppression is a debilitating and involves a high risk of inducing a secondary<br />

tumour and life-threatening infections.<br />

These are the reasons why its use is very limited and it is only suitable <strong>for</strong> patients<br />

<strong>with</strong> nephropathy who require a kidney transplant due to end-stage renal failure.<br />

In this case, the two transplants are per<strong>for</strong>med simultaneously. Pancreas transplantations<br />

have good graft survival percentages, good insulin independence results<br />

among recipients, as well as good secondary prevention of macrovascular and microvascular<br />

complications.<br />

Islet transplantation<br />

Pancreatic islet transplantation is more interesting due to its future prospects. This<br />

type of transplantation involves the administration of an extract of pancreatic islets –<br />

the group of pancreatic cells which include insulin-producing ß-cells. Unlike pancreatic<br />

transplantation, it is not a major surgical procedure: it is per<strong>for</strong>med by injecting<br />

the pancreatic extract into the portal vein which leads to the liver, the target organ in<br />

which the islets will be implanted and should survive.<br />

The technique itself does not pose particular difficulties, it can be repeated and<br />

does not involve the risks of major surgery. This procedure also involves issues related<br />

to compatibility and immunosuppression, which, as has been said, has relevant side<br />

effects and must be administered <strong>for</strong> life. Another obstacle concerns the limited survival<br />

of pancreatic islets as they are identified and destroyed by the patient’s immune<br />

system <strong>with</strong>in a year or two from transplantation, making it necessary to return to insulin<br />

therapy. Different protocols are underway to determine the best assortment of<br />

immunosuppressive medication and different transplant locations – <strong>for</strong> example the<br />

bone marrow – in order to achieve longer survival.<br />

( 109


The future of <strong>people</strong> <strong>with</strong> <strong>diabetes</strong><br />

Stem Cell Transplantation<br />

This is a very active subject of research in <strong>diabetes</strong>. In fact, difficulties in obtaining<br />

pancreatic tissue <strong>for</strong> the transplantation of islets will be crucial in the medium term.<br />

Un<strong>for</strong>tunately, studies on the generation specialized pancreatic cells from totipotent<br />

stem cells have shown limited results although an enormous progress is continuously<br />

being made.<br />

Prevention and treatment<br />

of complications<br />

Researchers are trying to identify biological markers that may precociously predict the<br />

development of <strong>diabetes</strong> complications and there<strong>for</strong>e prevent or delay their onset. Research<br />

on certain medications and proteins such as acetylsalicylic acid and C-peptide<br />

(insulin’s connecting peptide) are under way.<br />

110 )<br />

Artificial pancreas<br />

This technological tool involves an automatic and glucose sensor-drived continuous<br />

subcutaneous infusion of insulin. It comrpises a programmable insulin pump which<br />

administers insulin subcutaneously or in the peritoneum and a subcutaneous glucose<br />

sensor which continuously determines interstitial glucose levels. A computer algorithm<br />

manages the administration of the insulin by evaluating the data from the glucose<br />

sensor. Some artificial pancreas designs also include a glucagon pump.<br />

It might still take some time be<strong>for</strong>e a true artificial pancreas – a fully automatic<br />

pump – is achieved. This is due to two major limitations: the duration of insulin and<br />

the accuracy of the glucose sensor. There is also some concern due to the risk of technical<br />

malfunctions which may lead to excessive or insufficient insulin administration.<br />

However, these tools may lead to the normalization of blood glucose and consequently<br />

a drastic reduction in <strong>diabetes</strong> complications <strong>with</strong>out causing a significant increase<br />

in hypoglycaemia. If this technology will be effective in doing so, it may represent an<br />

optimal solution until effective biological and immunological therapies are developed.<br />

There is a cure <strong>for</strong> <strong>diabetes</strong> and research will find it.


SOStegno70 - Insieme ai ragazzi diabetici<br />

Sede operativa: Clinica Pediatrica<br />

Ospedale San Raffaele, Via Olgettina, 60 – 20132 Milano<br />

Tel. e Fax + 39 02.2643.3403<br />

Sezione di Brescia: Azienda Ospedaliera Spedali Civili<br />

Clinica Pediatrica, Piazzale Spedali Civili, 1 – 25123 Brescia<br />

Tel. 338.6844921<br />

Centro Regionale di Riferimento per la Diabetologia Pediatrica<br />

Centro di Endocrinologia dell’Infanzia e dell’Adolescenza<br />

Clinica Pediatrica – Ospedale San Raffaele<br />

Istituto di Ricovero e Cura a Carattere Scientifico<br />

Via Olgettina, 60 - 20132 Milano<br />

Per appuntamenti: Tel. 02-2643.2643<br />

Reparto di Pediatria: Tel. 02-2643.2622

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