Insulin resistance is an impaired metabolic response
to our body's own insulin so that active muscle cells
cannot take up glucose as easily as they should. In
that situation, the blood insulin levels are chronically
higher which inhibits our fat cells from giving up
their energy stores to let us lose weight. This disorder
is associated with obesity, hypertension, abnormal
triglycerides, glucose intolerance (syndrome 'X")
and Type 2 diabetes mellitus. Many women with polycystic
ovaries have this as well as women who have gestational
diabetes in pregnancy. Up to 50% of patients with
hypertension are estimated to have insulin resistance.
The main problem is that this condition can exist
unrecognized and metabolic damage can occur before
a full blown Type 2 diabetes is finally diagnosed.
Insulin resistant diabetics are 2-5 times more likely
to die from heart attack or stroke than are non diabetics.
While the complete mechanism of this disease is as
yet unknown, a recent article, Granberry MC, Fonseca
VA:Insulin resistance syndrome: Options for treatment.
South Med J 1999. 92:2-14, looks at what can be done
to treat this entity before it has a chance to cause
permanent metabolic damage.
What are risk factors for insulin resistance?
Many of the risk factors are the same as they are
for developing diabetes. Women who are overweight,
especially with central obesity, a strong family history
of diabetes, a history of gestational diabetes in
pregnancy, hypertension, women with dyslipidemia especially
having low HDL cholesterol and high triglycerides,
and women with polycystic ovary syndrome. Another
strong predictor is a skin change called acanthosis
nigricans which is a velvety, mossy, flat warty-like,
darkened skin change occurring at the neck, the armpits
(axillae) and underneath the breasts. Almost 90% of
women with these skin changes have insulin resisitance.
Additionally, insulin resistance may be worsened by
reduced physicial activity, aging, tobacco smoking,
or drugs such as diuretics, certain anti-hypertensives,
or steroids.
How is insulin resistance syndrome diagnosed?
The "gold standard" for diagnosis is a test
called the hyperinsulinemic euglycemic clamp study.
It is a complicated and expensive study in which insulin
and glucose is infused intravenously at several different
doses to see what levels of insulin control different
levels of glucose. Most physicians use fasting insulin
levels of over 15 uU/ml to diagnose it because they
have been shown to highly correlate with the euglycemic
clamp study. Some doctors use a fasting glucose to
insulin ratio or even a hemoglobin A1c to determine
if further testing is needed. Remember that the main
reason to diagnose insulin resisitance is to go further
on to look for Type 2 diabetes. This is diagnosed
by a 2 hour post 75 gram glucose load blood sugar
of over 200mg/dl, a random blood sugar of over 200
mg/dl, or a fasting glucose of over 127 mg/dl. Most
doctors would agree that if there was only impaired
glucose tolerance -- fasting plasma glucose >=
110 mg.dl and <127 mg/dl, or 2 hour post 75 gm
glucose load >=140 mg/dl and <200 mg/dl, --
and addtionally there was an elevated fasting insulin
level, then dietary control at least should be begun
as soon as possible.
What are the treatments available to improve
insulin sensitivity?
Treatment is based on improving glucose control and
preventing complications, especially cardiovascular
disease. Diet is a mainstay of treatment along with
exercise and weight loss. A low calorie diet reduces
insulin resistance in days even before much weight
loss takes place. Ten to twenty pounds (5-10 kg) substantially
helps glycemic control and a loss of 16% of body weight
improves glucose metabolism by a 100%.
Medications such as metformin (Glucophage®),
troglitazone (Rezulin®), and acarbose (Precose®),
alone or in combination, have been used to improve
insulin sensitivity mainly by reducing plasma glucose
by different mechanisms. All of these treatments can
be employed to prevent the development of Type 2 diabetes.
What specifically should I say to my doctor
if I want to be checked?
If you have any one of the following risk factors
for insulin resistance or Type 2 diabetes, tell your
doctor why you are at risk.
have a family history of type 2 diabetes
have high blood pressure
have central obesity with a waist circumferance (at
the navel) to hip circumferance ratio of more than
0.8 or have a body mass index over 27
have a low HDL level or elevated triglycerides
have atherosclerotic or coronary heart disease
have polycystic ovarian syndrome
have a history of gestational diabetes in pregnancy
have darkened skin changes in the neck, axillary and/or
breast folds consistent with acanthosis nigracans
Ask your doctor to order a fasting insulin level (look
for over 15uU/ml) or a fasting plasma glucose and
a 2 hour plasma glucose after a 75 gram oral glucose
load. If the doctor suggests a hyperinsulinemic euglycemic
clamp study or an intravenous 75 gram glucose tolerance
test instead, go along with those because they sometimes
can improve on diagnosis.
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