C h a p t e r 3 3
Diabetes Mellitus and the Metabolic Syndrome
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The diabetic diet has undergone marked changes
over the years, particularly in the recommendations for
distribution of calories among carbohydrates, proteins,
and fats. There no longer is a generic diabetic or ADA
diet, but rather an individualized dietary prescription
based on metabolic parameters, medical history of fac-
tors such as renal impairment and gastrointestinal auto-
nomic neuropathy, and treatment goals. For a person
with type 1 diabetes, eating consistent amounts and
types of food at specific and routine times is encour-
aged. Home blood glucose monitoring is used to fine-
tune the plan. Most people with type 2 diabetes are
overweight; thus nutrition therapy focuses on achieving
glucose, lipid, and blood pressure goals, and weight loss
if indicated. Mild to moderate weight loss (5% to 10%
of total body weight) has been shown to improve diabe-
tes control, even if desirable weight is not achieved.
Exercise
The benefits of exercise for anyone include increased
cardiovascular fitness and psychological well-being. For
many people with type 2 diabetes, the benefits of exer-
cise include a decrease in body fat, better weight con-
trol, and improvement in insulin sensitivity.
11,30
Exercise
is so important in diabetes management that an indi-
vidualized program of regular exercise usually is consid-
ered an integral part of the therapeutic regimen for every
diabetic. In general, sporadic exercise has only transient
benefits; a regular program is necessary for cardiovascu-
lar conditioning and to maintain a muscle–fat ratio that
enhances peripheral insulin receptivity.
In people with diabetes, the beneficial effects of exer-
cise are accompanied by an increased risk of hypogly-
cemia. Although muscle uptake of glucose increases
significantly, the ability to maintain blood glucose lev-
els is hampered by failure to suppress the absorption
of injected insulin and activate the counterregulatory
mechanisms that maintain blood glucose. Not only is
there an inability to suppress insulin levels, but insulin
absorption may also increase. This increased absorp-
tion is more pronounced when insulin is injected
into the subcutaneous tissue of the exercised muscle,
but it occurs even when insulin is injected into other
body areas. Even after exercise ceases, insulin’s lower-
ing effect on blood glucose continues. In some people
with type 1 diabetes, the symptoms of hypoglycemia
occur several hours after cessation of exercise, perhaps
because subsequent insulin doses (in people using mul-
tiple daily insulin injections) are not adjusted to accom-
modate the exercise-induced decrease in blood glucose.
The cause of hypoglycemia in people who do not
administer a subsequent insulin dose is unclear. It may
be related to the fact that the liver and skeletal mus-
cles increase their uptake of glucose after exercise as a
means of replenishing their glycogen stores, or that the
liver and skeletal muscles are more sensitive to insulin
during this time. People with diabetes should be aware
that delayed hypoglycemia can occur after exercise and
that they may need to alter their diabetes medication
dose, their carbohydrate intake, or both.
Although of benefit to people with diabetes, exer-
cise must be weighed on the risk–benefit scale. Before
beginning an exercise program, persons with diabe-
tes should undergo an appropriate evaluation for
macrovascular and microvascular disease.
30
The goal
of exercise is safe participation in activities consis-
tent with an individual’s lifestyle. As with nutrition
guidelines, exercise recommendations need to be indi-
vidualized. Considerations include the potential for
hypoglycemia, hyperglycemia, ketosis, cardiovascular
ischemia and arrhythmias (particularly silent isch-
emic heart disease), exacerbation of proliferative reti-
nopathy, and lower extremity injury. For those with
chronic diabetes, the complications of vigorous exer-
cise can be harmful and cause eye hemorrhage and
other problems.
Oral and Injectable Antidiabetic Agents
Historically, two categories of antidiabetic agents existed:
insulin injections and oral medications. However, this
classification has been set aside since the introduc-
tion of new injectable non-insulin antidiabetic agents.
Because people with type 1 diabetes are deficient in insu-
lin, they are in need of exogenous insulin replacement
therapy from the start. People with type 2 diabetes can
have increased hepatic glucose production, decreased
peripheral utilization of glucose, decreased utilization
of ingested carbohydrates, and, over time, impaired
insulin secretion and excessive glucagon secretion from
the pancreas (Fig. 33-8). The antidiabetic (non-insulin)
agents used in the treatment of type 2 diabetes (insulin
secretagogues, biguanides,
α
-glucosidase inhibitors, thi-
azolidinediones, SGLT2 inhibitors, and incretin-based
agents) attack each one of these areas and sometimes
all.
31,32
If good glycemic control cannot be achieved with
one or a combination of non-insulin agents, insulin can
be added or used by itself.
Insulin Secretagogues.
The insulin secretagogues act
at the level of the pancreatic beta cells to stimulate insu-
lin secretion. There are two general classes of insulin
secretagogues: (1) sulfonylureas and (2) meglitinides.
32
Both types require the presence of functioning beta cells,
are used only in the treatment of type 2 diabetes, and
have the potential for producing hypoglycemia.
The control of insulin release from the pancreatic
beta cells by glucose or the sulfonylurea drugs requires
the generation of adenosine triphosphate (ATP), closing
of an ATP-gated potassium channel, and opening of a
transmembrane calcium channel.
32
The sulfonylureas
(e.g., glipizide, glyburide, glimepiride) act by binding
to a high-affinity sulfonylurea receptor on the beta cell
that is linked to an ATP-sensitive potassium channel
(Fig. 33-9). Binding of a sulfonylurea closes the channel,
resulting in a coupled reaction that leads to an influx
of calcium ions and insulin secretion. Because the sul-
fonylureas increase insulin levels and the rate at which
glucose is removed from the blood, it is important to
recognize that they can cause hypoglycemic reactions.
This problem is more common in elderly people with
