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P A R T 6
Drugs acting on the endocrine system
(increased thirst) occurs because the tonicity of the blood
is increased owing to the increased glucose and waste
products in the blood and the loss of fluid with glucose
in the urine. The hypothalamic cells that are sensitive to
fluid levels sense a need to increase fluid in the system,
which in turn causes the person to feel thirsty.
Lipolysis, or fat breakdown, occurs as the body
breaks down stored fat into FFAs for energy because
glucose is not usable. The person experiences
ketosis
as
metabolism shifts to the use of fat for energy. Ketones
are produced that cannot be removed effectively.
Acidosis also occurs because the liver cannot remove
all of the waste products (acid being a primary waste
product) that result from the breakdown of glucose, fat
and proteins. Muscles break down because proteins are
being broken down for their essential amino acids. The
breakdown of proteins results in an increase in nitrogen
wastes, which is manifested by an elevated blood urea
nitrogen (BUN) concentration and sometimes by protein
in the urine. People with hyperglycaemia do not heal
quickly because of this protein breakdown, as well as
the lack of a stimulus to initiate protein building. All
of these actions eventually contribute to development of
the complications associated with chronic hyperglycae-
mia or diabetes.
DIABETES MELLITUS
Diabetes mellitus (literally, “honey urine”) is character-
ised by complex disturbances in metabolism. Diabetes
affects carbohydrate, protein and fat metabolism. The
most frequently recognised clinical signs of diabetes
are hyperglycaemia (fasting blood sugar level greater
than 8.0 mmol/L [106 mg/dL]) and glycosuria (the
presence of sugar in the urine). The alteration in the
body’s ability to effectively deal with carbohydrate, fat
and protein metabolism over the long term results in a
thickening of the basement membrane (a thin layer of
collagen filament that lies just below the endothelial
lining of blood vessels) in large and small blood vessels.
This thickening leads to changes in oxygenation of the
vessel lining; damage to the vessel lining, which leads
to narrowing, vessel remodelling and decreased blood
flow through the vessel; and an inability of oxygen to
rapidly diffuse across the membrane to the tissues. These
changes result in an increased incidence of a number of
disorders, including the following:
Endocrine:
Diabetes
•
Atherosclerosis
: Heart attacks and strokes related
to the development of atherosclerotic plaques in the
vessel lining
•
Retinopathy
: Resultant loss of vision as tiny vessels in
the eye are narrowed and closed
•
Neuropathies
: Motor and sensory changes in the feet
and legs and progressive changes in other nerves as
the oxygen supply to these nerves is slowly cut off
•
Nephropathy
: Renal dysfunction related to changes in
the basement membrane of the glomerulus
The overall metabolic disturbances associated
with diabetes are thought to be caused by a mosaic
of problems, including low insulin and loss of insulin
receptor sensitivity.
The diagnosis of diabetes mellitus has involved
monitoring of fasting blood glucose levels and sometimes
challenging the system with glucose for a glucose toler-
ance test. However, recent research indicates that the
body’s response to food may be a more important indi-
cator of impending diabetes. Current thinking is that a
fasting blood glucose level may not be as important as
a postprandial (after a meal) blood glucose level, which
reveals the body’s ability to respond to a glucose chal-
lenge. The importance of looking at a variety of different
glucose markers is being stressed. Box 38.3 highlights
some cultural variations in blood glucose levels.
Glycosylated haemoglobin
levels, or an HbA
1c
test,
provide a 3-month average of glucose levels. Red blood
cells are freely permeable to glucose, and this test gives
an average range of glucose exposure over the life of the
red blood cell (about 120 days). This test does not require
fasting before blood is drawn or the oral intake of glucose
before testing. Elevations above 6% may be an early indi-
cator of a prediabetic state, before changes are noted in
the fasting blood sugar level. Once a baseline is estab-
lished, the goal of therapy for a diabetic individual is an
HbA
1c
level less than 7%. Researchers believe that very
early intervention—diet, exercise and lifestyle changes—
may delay the onset of diabetes and the complications,
including coronary artery disease, that come with it.
Diabetes mellitus is classified as either type 1, once
called insulin-dependent diabetes mellitus (IDDM), or
type 2, once called non–insulin-dependent diabetes
mellitus (NIDDM) or adult-onset diabetes. Type 1
diabetes is usually associated with rapid onset, mostly
in younger people, and is connected in many cases to
viral destruction of the beta cells of the pancreas. Type 1
diabetes always requires insulin replacement because the
beta cells are no longer functioning.
Type 2 diabetes was once thought to be a disease
of mature adults with a slow and progressive onset.
However, studies released in 2001 reported that the
incidence of type 2 diabetes in teenagers and young
adults is increasing markedly. People with type 2
diabetes are able to produce insulin, but perhaps not
enough to maintain glucose control, or perhaps their
insulin receptors are not sensitive enough to insulin,
leading to increased serum glucose levels.
Questions are being raised about the impact of early
diet and lack of exercise in contributing to this new
