Womens Health

Insulin Resistance Syndrome

Frederick R. Jelovsek MD

What Is Insulin Resistance?

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?

  1. 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
  2. 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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