Insulin resistance: A risk factor for diabetic complications

Glucose tolerance, as estimated by the oral glucose tolerance test, depends upon several factors, the most important of which are insulin secretion and insulin action. A close correlation between the two variables, insulin secretion and insulin action, has been found in normal subjects, where they seem to compensate for each other. The result is that glucose tolerance is kept normal even if one of the variables is altered.3 Thus, most subjects with insulin resistance may compensate by hypersecretion of insulin. These subjects, therefore, will develop hyperinsulinemia both in the fasting state and after a meal. If beta cells are unable to produce enough insulin to overcome the insulin resistance, frank diabetes mellitus will be the result. Insulin resistance, therefore, may be present in a compensated form e.g., obesity, and an uncompensated form e.g., noninsulin-dependent diabetes mellitus (NIDDM). In between normal glucose tolerance and frank diabetes (fasting hyperglycemia), a clinical state characterized by partial compensation of insulin resistance has been defined, impaired glucose tolerance (IGT), a clinical state with normal fasting plasma glucose values, but postprandial hyperglycemia. Glucose intolerance, both as diabetes mellitus and IGT, has been shown to be linked to macrovascular diseases, especially CHD.4 Furthermore, glucose intolerance seems to be a common feature of subjects with arterial hypertension. In a recent paper, about 40% of the hypertensives were glucose intolerant,5 while dyslipoproteinemic subjects have been shown to be more glucose intolerant than controls.* Taken together, glucose intolerance seems to be a common characteristic of subjects with dyslipoproteinemia, arterial hypertension, and/or obesity. Since insulin resistance is the major underlying defect in glucose intolerance in the subjects described above, the following question may be raised: How can insulin resistance lead to hypertension, obesity, and dyslipoproinemia?