Clinical Pharmacology and Therapeutics

286 DIABETES MELLITUS
can cause retinal haemorrhage and blindness. Cataracts are
common. Diabetic neuropathy causes a glove and stocking
distribution of loss of sensation with associated painful
paraesthesiae. Approximately one-third of diabetic patients
develop diabetic nephropathy, which leads to renal failure.
Microalbuminuria is a forerunner of overt diabetic
nephropathy.
Macrovascular disease is the result of accelerated atheroma
and results in an increased incidence of myocardial infarction,
peripheral vascular disease and stroke. There is a strong association
(pointed out by Reaven in his 1988 Banting Lecture at
the annual meeting of the American Diabetes Association)
between diabetes and obesity, hypertension and dyslipidaemia
(especially hypertriglyceridaemia), and type 2 diabetes is
strongly associated with endothelial dysfunction, an early
event in atherogenesis (Chapter 27).
PRINCIPLES OF MANAGEMENT
It is important to define ambitious but achievable goals for each
patient. In young type 1 patients there is good evidence that
improved diabetic control reduces microvascular complications.
It is well worth trying hard to minimize the metabolic derangement
associated with diabetes mellitus in order to reduce the
development of such complications. Education and support are
essential to motivate the patient to learn how to adjust their
insulin dose to optimize glycaemic control. This can only be
achieved by the patient performing blood glucose monitoring at
home and learning to adjust their insulin dose accordingly. The
treatment regimen must be individualized. A common strategy
is to combine injections of a short-acting insulin before each
meal with a once daily injection of a long-acting insulin to provide
a low steady background level during the night. Follow up
must include structured care with assessment of chronic glycaemic
control using HbA1c and regular screening for evidence
of microvascular disease. This is especially important in the case
of proliferative retinopathy and maculopathy, because prophylactic
laser therapy can prevent blindness.
By contrast, striving for tight control of blood sugar in type 2
patients is only appropriate in selected cases. Tight control
reduces macrovascular complications, but at the expense of
increased hypoglycaemic attacks, and the number of patients
that needs to be treated in this way to prevent one cardiovascular
event is large. In contrast, aggressive treatment of hypertension
is of substantial benefit, and the target blood pressure
should be lower than in non-diabetic patients (130 mmHg systolic
and 80 mmHg diastolic, see Chapter 28). In older type 2
patients, hypoglycaemic treatment aims to minimize symptoms
of polyuria, polydipsia or recurrent Candida infection, and to prevent
hyperosmolar coma.
DIET IN DIABETES MELLITUS
It is important to achieve and maintain ideal body weight on a
non-atherogenic diet. Caloric intake must be matched with
insulin injections. Patients who rely on injected insulin must
time their food intake accordingly. Simple sugars should be
restricted because they are rapidly absorbed, causing postprandial
hyperglycaemia, and should be replaced by foods
that give rise to delayed and reduced glucose absorption,
analogous to slow release drugs (quantified by nutritionists as
‘glycaemic index’). (Artificial sweeteners are useful for those
with a ‘sweet tooth’.) A fibre-rich diet reduces peak glucose
levels after meals and reduces the insulin requirement. Beans
and lentils flatten the glucose absorption curve. Saturated fat
and cholesterol intake should be minimized. Low fat sources
of protein are favoured. There is no place for commercially
promoted ‘special diabetic foods’, which are expensive and
also often high in fat and calories at the expense of complex
carbohydrate.
DRUGS USED TO TREAT DIABETES MELLITUS
INSULINS
Insulin is a polypeptide. Animal insulins have been almost
entirely replaced by recombinant human insulin and related
analogues. These are of consistent quality and cause fewer
allergic effects. Insulin is available in several formulations
(e.g. with protamine and/or with zinc) which differ in pharmacokinetic
properties, especially their rates of absorption
and durations of action. So-called ‘designer’ insulins are synthetic
polypeptides closely related to insulin, but with small
changes in amino acid composition which change their properties.
For example, a lysine and a proline residue are
switched in insulin lispro, which consequently has a very
rapid absorption and onset (and can therefore be injected
immediately before a meal), whereas insulin glargine is very
slow acting and is used to provide a low level of insulin activity
during the 24-hour period.
Use
Insulin is indicated in all patients with type 1 diabetes mellitus
(although it is not strictly necessary during the early ‘honeymoon’
period before islet cell destruction is complete) and
in about one-third of patients with type 2 disease. Insulin is
usually administered by subcutaneous injection, although
recently an inhaled preparation has been licensed for use in
type 2 diabetics. (Note: This was not commercially successful,
and has been withdrawn in the UK for this reason.) The effective
dose of human insulin is usually rather less than that of
animal insulins because of the lack of production of blocking
antibodies. Consequently, the dose is reduced when switching
from animal to human insulin.
Soluble insulin is the only preparation suitable for intravenous
use. It is administered intravenously in diabetic emergencies
and given subcutaneously before meals in chronic
management. Formulations of human insulins are available in
various ratios of short-acting and longer-lasting forms (e.g.
30:70, commonly used twice daily). Some of these are marketed