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Ten key facts on insulin resistance

Diabetes and Primary Care, Summer, 2003 by Michael Mead

Introduction

To improve diabetes care for our population, primary care must have a fundamental understanding of the role of insulin resistance in the pathogenesis of diabetes and in producing the increased risk of cardiovascular disease. In this article I summarise what a primary care professional needs to know to enable the effective targeting of insulin resistance in their daily surgeries.

Insulin resistance is a fundamental cause of type 2 diabetes: 92% of people with type 2 diabetes have insulin resistance (Haffner, 1999) and it has been suggested that this develops 20-30 years before the onset of type 2 diabetes (Beck-Neilsen and EGIR, 1999). An understanding of research should lead to the development of strategies to target insulin resistance at a primary care level and thus reduce the number of people with type 2 diabetes and the associated complications.

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FACT 1: A knowledge of insulin resistance is key to the understanding of type 2 diabetes

Insulin resistance plays a fundamental role in the pathogenesis of type 2 diabetes and its complications. Understanding insulin resistance enables us to effectively target ways of preventing both the development of type 2 diabetes and its major complications.

In essence, insulin resistance is a decrease in the sensitivity of tissues such as the liver, skeletal muscle and adipose tissue to the action of insulin. In the liver the result of impaired sensitivity to insulin is an increase in hepatic glucose production. In the other tissues the result of insulin resistance is a decreased uptake of glucose. Both processes lead to a net rise in the blood glucose. The body's response to this rise in glucose levels is for the [beta] cells to secrete more insulin. The first progression towards type 2 diabetes therefore is a hyperinsulinaemia and impaired glucose tolerance (IGT), with increases in post prandial glucose concentrations. Most patients stay at this level for a considerable time with the excess insulin produced just matching the blood glucose levels.

However, in time the [beta] cells begin to fail and are unable to produce sufficient insulin to stabilise the raised blood glucose, leading to the development of type 2 diabetes. Insulin resistance affects about a quarter of the population and one in seven adults have IGT (Reaven, 1994); 50% of these patients develop diabetes within 10 years.

FACT 2: Insulin resistance is the major risk factor for cardiovascular disease in type 2 diabetes

Cardiovascular disease causes 70-75% of deaths in people with type 2 diabetes (Kings Fund Policy Institute, 1996). Insulin resistance increases the risk of cardiovascular disease, preceding the actual development of type 2 diabetes. Patients with hyperinsulinaemia have been shown to have an increased risk of cardiovascular disease (Ruige et al, 1998). The reason for this increased risk lies with the metabolic and systemic changes associated with insulin resistance: insulin resistance syndrome.

The key features of insulin resistance syndrome are:

* Hyperinsulinaemia and impaired glucose tolerance (IGT). Increased cardiovascular risk has also been demonstrated in patients with IGT (Jarrett et al, 1982).

* Hypertension. This is a well known cardiovascular risk factor, particularly important in people with diabetes. Insulin can produce vasodilation in normal patients and this vasodilation is impaired in people with insulin resistance. Hyperinsulinaemia can result in increased reabsorption of sodium and water by kidney tubular cells and an overactive sympathetic system has also been postulated as one of the causes of hypertension in the obese insulin resistant patient (Ginsberg, 2000).

* Dyslipidaemia may be the most serious effect of insulin resistance. Insulin results in free fatty acids being released from adipose tissue into the bloodstream. The liver responds by increasing triglycerides, and this increases high density lipoprotein (HDL) excretion, lowering the HDL cholesterol. These changes also result in a shift of low density lipoproteins (LDL) to a more atherogenic form: small dense LDL. The net result is a combination of raised triglycerides, a low HDL cholesterol and an increase in small dense LDL cholesterol: an atherogenic mix known to substantially increase the risk of cardiovascular disease.

* Obesity (more correctly central obesity) is another component of insulin resistance syndrome. Obesity is a risk factor for cardiovascular disease and for the development of type 2 diabetes.

* Acceleration and increase in severity of atherosclerosis. There is evidence that insulin resistance may act directly via pathways in vascular smooth muscle cells, to promote atherosclerosis (Ginsberg, 2000)

* Increase in blood coagulability, with impaired fibrinolysis (see fact 8 for more information).

* Hyperuricaemia is included by some as part of the syndrome.

FACT 3: The two most important environmental factors for insulin resistance (and type 2 diabetes) are lack of exercise and obesity

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Ten key facts on insulin resistance

Diabetes and Primary Care, Summer, 2003 by Michael Mead

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