Insulin Resistance, Insulin Resistance Syndrome and Race

I often hear clinicians say that they are not too clear about the differences between insulin resistance and insulin resistance syndrome. Let me define them, and then tell you why they are so important, and why everyone needs to be informed about them.

First, insulin is a hormone produced primarily in the cells of the Islets of Langerhans in the pancreas. It has over 500 functions in the human body, but its main actions are on the regulation of the metabolism of carbohydrates and fats. Insulin enables glucose – one of the major sources of energy – to move into many of the cells in the body. Insulin is also involved in the conversion of glucose to glycogen. These two actions lower the blood glucose level.

Insulin resistance is defined as an impaired biological response to insulin. It is a condition in which many of the cells of the body – mainly in the liver, fat and muscle – become resistant to the effects of insulin. The normal responses to a given amount of insulin are reduced. As a result, higher levels of insulin are needed in order for insulin to have its effects. There are many potential causes of insulin resistance: genetic; an increase in intra-abdominal fat; smoking cigarettes; being of low birth weight; and there are some prescription medicines that can cause insulin resistance. Insulin resistance is one of the underlying causes of type 2 (maturity onset) diabetes mellitus, as well as an array of other illnesses including polycystic ovarian syndrome. Most studies have suggested that around a third of people living in the United States and Western Europe have insulin resistance, and there are marked ethnic differences.

The insulin resistance syndrome has several other names: Metabolic syndrome; (Metabolic) Syndrome X; Dysmetabolic syndrome; Reaven’s syndrome; multiple metabolic syndrome. There are several sets of criteria for defining the insulin resistance syndrome. In the USA it is usually defined as the presence of 3 or more of the following:
1. Abdominal obesity (Waist circumference >40 inches in men; >35 inches in women
2. Glucose intolerance (fasting glucose ≥110 mg/dL)
3. Elevated blood pressure ≥130/85 mmHg
4. Triglycerides >150 mg/dL
5. Low HDL (Men: <40 mg/dL; women: <50 mg/dL)

There is a constant debate in the medical literature about whether insulin resistance syndrome is an illness, and what should be included in it. It is important, because it appears to predict the development of diabetes and coronary artery disease, and between 20 and 25% of the population of the Western world has it. So what normally happens is that a person develops insulin resistance, which eventually evolves into the insulin resistance syndrome, before diabetes and heart disease appears. There can be as long as twelve years between the development of insulin resistance, and the diagnosis of diabetes, and we have very good evidence that lifestyle changes can dramatically reduce the risk of moving from insulin resistance to the insulin resistance syndrome and diabetes.

It has become quite well-known that people of African and Asian Indian heritage are at increased risk of developing insulin resistance, and some of the sequelae of insulin resistance: insulin resistance syndrome, diabetes mellitus, hypertension and gout. These may in turn lead to increased rates of myocardial infarction and strokes. A study presented last Monday at ENDO 2006, the annual meeting of the Endocrine Society in Boston helps further clarify some of these ethnic differences. Researchers analyzed data from the Insulin Resistance Atherosclerosis Study (IRAS), designed to assess relationships between insulin resistance and cardiovascular disease in a large multi-ethnic population.

The investigators divided data from female IRAS participants into different groups based on body mass index (BMI), a measure of body fat based on height and weight. A BMI of less than 25 is usually considered "normal." The analysis revealed that 47 percent of black women of normal weight had insulin resistance, compared to less than 20 percent of the Hispanic or White women. Both insulin resistance and the likelihood of developing type 2 diabetes increase as obesity increases. It had long been suspected that there was an independent effect of race, but this study not only shows that race alone may influence insulin resistance, but that we may therefore need to change the definition of obesity in women of African heritage.

The news reports on this important finding failed to mention that previous research has found something very similar in Asians from India, China and Japan. Each of these ethnic groups may develop insulin resistance, insulin resistance syndrome and diabetes without being obese, though obesity dramatically increases their risks of running into trouble.

It is relatively simple and inexpensive to measure insulin resistance, and many metabolic experts, including your humble reporter, have, for more than a decade, been measuring it in high-risk individuals. Clearly we cannot do anything much about an ethnic or genetic risk, but we can alter the way in which the body responds to that risk. If a person is insulin resistant, diet, exercise, specific nutritional and herbal interventions and occasionally medications, may all reduce the risk of developing diabetes and heart disease.

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