802
U N I T 9
Endocrine System
there often is a short period of improved beta cell func-
tion, during which symptoms of diabetes disappear
and insulin injections are reduced or not needed. This
is sometimes called the
honeymoon period.
Immune
interventions (immunomodulation) designed to inter-
rupt the destruction of beta cells before development of
type 1 diabetes are being investigated in various trials.
Unfortunately, none of the interventions studied to date
has shown real clinical utility.
IdiopathicType 1B Diabetes.
The term
idiopathic type
1B diabetes
is used to describe those cases of beta cell
destruction in which no evidence of autoimmunity is
present. Only a small number of people with type 1 dia-
betes fall into this category; most are of African or Asian
descent. Type 1B diabetes is strongly inherited. People
with the disorder have episodic DKA due to varying
degrees of insulin deficiency with periods of absolute
insulin deficiency that may come and go.
Type 2 Diabetes Mellitus and the Metabolic
Syndrome
Type 2 diabetes mellitus, previously described as
non–
insulin-dependent diabetes
, is a condition of hyperglyce-
mia that accompanies a
relative
rather than an
absolute
insulin deficiency (although insulin therapy may be
still be required for glycemic control).
3,10,11
It currently
accounts for about 90% to 95% of the cases of diabetes.
Most people with type 2 diabetes are overweight and
older. Recently, however, type 2 diabetes has become a
more common occurrence in obese children and ado-
lescents.
12,13
Although type 1 diabetes remains the main
form of diabetes in children worldwide, it seems likely
that type 2 diabetes will become the predominant form
within 10 years in some ethnic groups.
13
Metabolic Abnormalities Involved in Type 2
Diabetes.
The metabolic abnormalities involved in type
2 diabetes include (1) insulin resistance, (2) increased
glucose production by the liver, and (3) impaired secre-
tion of insulin by the pancreatic beta cells
14–16
(Fig. 33-7).
Insulin resistance, which can be defined as the fail-
ure of target tissues to respond to insulin, predates the
development of hyperglycemia. That is, in the early
stages of the evolution of type 2 diabetes, insulin resis-
tance is usually accompanied by compensatory beta cell
hyperfunction and hyperinsulinemia.
In skeletal muscle, insulin resistance prompts
decreased uptake of glucose. Although muscle glucose
uptake is slightly increased after a meal, the efficiency
with which it is taken up (glucose clearance) is dimin-
ished, resulting in an increase in
postprandial
(following
a meal) blood glucose levels.
16
In contrast, in the liver, insulin resistance leads to
impaired suppression of glucose production with an
overproduction of glucose despite a fasting hyperinsu-
linemia. In fact, the excessive rate of hepatic glucose
production is the primary determinant of elevated FPG
in persons with type 2 diabetes.
15,16
Several mechanisms can lead to impaired secretion
of insulin by the pancreatic beta cells. These include
an initial decrease in beta cell mass related to genetic
or epigenetic factors, increased apoptosis or decreased
regeneration of beta cells, or beta cell exhaustion due
to long-standing insulin resistance.
15
According to one
study, beta cell function was reduced by an average of
50% at the time of diagnosis in type 2 diabetes, and
Genetic
predisposition
Deranged insulin
release
Increased
hepatic glucose
output
Insulin
resistance
Decreased glucose
uptake
Hyperglycemia
Type 2
diabetes
Environmental
factors
Obesity
FIGURE 33-7.
Pathogenesis of type 2 diabetes
mellitus.
