C h a p t e r 3 3
Diabetes Mellitus and the Metabolic Syndrome
799
growth hormone levels that occur during periods of stress
and periods of growth in children can produce the entire
spectrum of metabolic abnormalities associated with poor
regulation, despite optimized insulin treatment.
Glucocorticoid Hormones.
The glucocorticoid hor-
mones, which are synthesized in the adrenal cortex
along with other corticosteroid hormones, are critical
to survival during periods of fasting and starvation.
They stimulate gluconeogenesis by the liver, sometimes
producing a 6- to 10-fold increase in hepatic glucose
production. These hormones also moderately decrease
tissue use of glucose.
There are several steroid hormones with glucocor-
ticoid activity; the most important of these is cortisol,
which accounts for approximately 95% of all gluco-
corticoid activity (see Chapter 32). Almost any type of
stress, whether physical or emotional, causes an imme-
diate increase in adrenocorticotropic hormone (ACTH)
secretion by the anterior pituitary gland, followed within
minutes by greatly increased secretion of cortisol by the
adrenal gland. Hypoglycemia is a potent stimulus for
cortisol secretion. In predisposed persons, the prolonged
elevation of glucocorticoid hormones can lead to hyper-
glycemia and the development of diabetes mellitus. In
people with diabetes, even transient increases in cortisol
can complicate control.
Diabetes Mellitus
The term
diabetes
is derived from a Greek word mean-
ing “going through,” and
mellitus
from the Latin word
for “honey” or “sweet.” Reports of the disorder can be
traced back to the first century
ad
, when Aretaeus the
Cappadocian described the disorder as a chronic afflic-
tion characterized by intense thirst and voluminous,
honey-sweet urine: “the melting down of flesh into
urine.” It was the discovery of insulin by Banting and
Best in 1922 that transformed the once-fatal disease into
a manageable chronic health problem.
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Diabetes is a disorder of carbohydrate, protein, and
fat metabolism resulting from a lack of insulin avail-
ability or a reduction in the biologic effects of insulin.
It can represent an absolute insulin deficiency, impaired
release of insulin by the pancreatic beta cells, inadequate
or defective insulin receptors or postreceptor regulation,
or the production of inactive insulin or insulin that is
destroyed before it can carry out its action.
Classification and Etiology
Although diabetes mellitus clearly is a disorder of insu-
lin availability, it is not a single disease. A revised clas-
sification system, which was developed in 1997 by the
Expert Committee on the Diagnosis and Classification
of Diabetes Mellitus, divides diabetes into four clinical
acids in the body. Because fatty acids cannot
be converted to glucose, the body must break
down proteins and use the amino acids for
gluconeogenesis.
■■
Energy metabolism is controlled by a number
of hormones, including insulin, glucagon,
epinephrine, growth hormone, and the
glucocorticoids. Of these hormones, only insulin
has the effect of lowering the blood glucose
level. It does this by facilitating the transport
of glucose into body cells and decreasing the
liver’s production and release of glucose into
the bloodstream. Insulin also has the effect of
decreasing lipolysis and the use of fats as a fuel
source.
■■
Other hormones—glucagon, epinephrine, growth
hormone, and the glucocorticoids—maintain or
increase blood glucose concentrations. Glucagon
and epinephrine promote glycogenolysis, and
glucagon and the glucocorticoids increase
gluconeogenesis. Epinephrine and glucagon also
increase the use of fat for energy by increasing
the release of fatty acids from adipose tissue
cells. Growth hormone decreases the peripheral
utilization of glucose.
SUMMARY CONCEPTS
■■
The body predominantly metabolizes glucose
and fatty acids for energy.The brain depends
exclusively on glucose for its energy. Body
tissues obtain glucose from the blood.The liver
stores excess glucose as glycogen and it uses
gluconeogenesis to convert amino acids, lactate,
and glycerol into glucose during fasting or when
glucose intake does not keep pace with demand.
■■
Blood glucose levels reflect the difference
between the amount of glucose released into the
circulation by the liver and the amount of glucose
removed from the blood by body tissues. Fats,
which serve as an efficient source of fuel for the
body, are stored in adipose tissue as triglycerides,
which consist of three fatty acids linked to a
glycerol molecule. In situations that favor fat
breakdown, such as fasting or diabetes mellitus,
the triglycerides in adipose tissue are broken down
and the fatty acids are used as fuel or transported
to the liver, where they are converted to ketones.
■■
Proteins, which are made up of amino acids, are
essential for the formation of all body structures.
Unlike glucose and fatty acids, there is only
a limited facility for storage of excess amino
