DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

• Impaired glucose tolerance (IGT): Glucose level
between 7.8 and 11.1 mmol/L (140-199 mg/dL)
120 minutes after ingestion of 75 g liquid glucose
solution
• Diabetes mellitus (see Table 43–1)
The diagnosis of diabetes mellitus is currently
based on the correlation of a diabetes-specific complication
with a particular level of glycemia, that is, the
level of glycemia at which a diabetes-specific complication
like retinopathy begins to appear. The boundaries
between normal glucose homeostasis, abnormal glucose
homeostasis, and diabetes are described as abrupt
transitions, but the data are best viewed as a spectrum.
Organizations such as the American Diabetes
Association (ADA) and the World Health Organization
(WHO) have adopted criteria for the diagnosis of diabetes,
based on the fasting blood glucose, the glucose
value following an oral glucose challenge, or the level
of hemoglobin A 1c
(HbA 1c
; exposure of proteins to elevated
[glucose] produces nonenzymatic glycation of
proteins including Hb. Thus the level of HbA 1c
represents
a measure of the average glucose concentration
to which the Hb has been exposed) (Table 43–1).
Fasting plasma glucose is most widely used because of
its convenience and low cost. The diagnostic criteria
have recently (2009) been changed to also include a
hemoglobin A 1c
(A1C) value ≥6.5%. Impaired fasting
glucose (IFG) and impaired glucose tolerance (IGT),
previously termed prediabetes, or an A1C of 5.7-6.4%
portend a markedly increased risk of progressing to
Table 43–1
Criteria for the Diagnosis of Diabetes
• Symptoms of diabetes plus random blood glucose concentration
≥11.1 mM (200 mg/dL) a or
• Fasting plasma glucose ≥7.0 mM (126 mg/dL) b or
• Two-hour plasma glucose ≥11.1 mM (200 mg/dL) during
an oral glucose tolerance test c
• HbA 1c
≥6.5%
a
Random is defined as without regard to time since the last meal.
b
Fasting is defined as no caloric intake for at least 8 h.
c
The test should be performed using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water; this test is
not recommended for routine clinical use.
Note: In the absence of unequivocal hyperglycemia and acute metabolic
decompensation, these criteria should be confirmed by repeat
testing on a different day.
Adapted from Diabetes Care, 2010; 33:S62-S69.
type 2 diabetes. An A1C of 5.7-6.4%, IFG, and IGT do
not identify the same group of individuals, but all are
associated with increased risk of cardiovascular disease.
The four broad categories of diabetes include type 1
diabetes, type 2 diabetes, other forms of diabetes, and
gestational diabetes (Table 43–2). Although hyperglycemia
is common to all forms of diabetes, the pathogenic
mechanisms leading to diabetes are quite
distinct. As our current understanding of the molecular
pathogenesis of the hyperglycemia improves, these categories
will likely be subdivided into a number of other
types of diabetes.
Screening for Diabetes and Categories of Increased Risk Of
Diabetes. Many individuals with type 2 diabetes are asymptomatic
at the time of diagnosis, and diabetes is often found on routine blood
testing as an outpatient or upon admission to the hospital for nonglucose-related
reasons. A long, asymptomatic phase in type 2 diabetes
(up to a decade) is likely responsible for the observation that up to
50% of individuals with diabetes may have a diabetes-related complication
at the time of diagnosis. For these reasons, the ADA recommends
widespread screening for type 2 diabetes of these individuals
with the following features:
• >45 years of age or
• Body mass index >25 kg/m 2 with one of these additional risk
factors: hypertension, low high-density lipoprotein, family history
of type 2 diabetes, high-risk ethnic group (African
American, Latino, Native American, Asian American, and Pacific
Islander), abnormal glucose testing (IFG, IGT, A1C of 5.7-6.4%),
cardiovascular disease, and women with polycystic ovary syndrome
or who have previously delivered a large infant.
Earlier diagnosis and treatment of type 2 diabetes should
delay diabetes-related complications and reduce the burden of the
disease. Many also feel that earlier treatment may alter the natural
history of the disease, but conclusive proof of this hypothesis is
lacking. Likewise, informing individuals who are at increased risk
for developing diabetes provides impetus to take steps to slow the
progression to diabetes. A number of interventions including pharmacological
agents and lifestyle modification are effective.
Screening for type 1 diabetes is not currently recommended.
Pathogenesis of Type 1 Diabetes. Type 1 diabetes
accounts for 5-10% of diabetes and results from
autoimmune-mediated destruction of the β cells of the
islet leading to total or near total insulin deficiency (von
Herrath et al., 2007). Prior terminology included juvenileonset
diabetes mellitus or insulin-dependent diabetes
mellitus. Although traditionally considered a disease of
children and adolescents, type 1 diabetes resulting
from autoimmune β cell destruction can occur at any
age. In fact, in some reports, more than one-third of
individuals developed type 1 diabetes after adolescence.
Individuals with type 1 diabetes and their families have
an increased prevalence of autoimmune diseases such
1243
CHAPTER 43
ENDOCRINE PANCREAS AND PHARMACOTHERAPY OF DIABETES MELLITUS AND HYPOGLYCEMIA