Resistance to insulin-stimulated glucose uptake and hyperinsulinemia: role in non-insulin-dependent diabetes, high blood pressure, dyslipidemia and coronary heart disease.

Patients with impaired glucose tolerance (IGT) and Type 2 diabetes have been shown to be more resistant to insulin-stimulated glucose uptake than individuals with normal glucose tolerance. Evidence has also been published showing that first degree relatives of patients with Type 2 diabetes are insulin resistant when compared to a matched group of relatives of subjects with normal glucose tolerance. In addition, it has recently been shown that the ability of insulin to stimulate glucose uptake varies approximately four-fold in individuals with normal glucose tolerance, and insulin resistance of a degree comparable to that seen in patients with IGT or with Type 2 diabetes is present in a significant portion of the normal population. Given a defect in insulin-stimulated glucose uptake, glucose tolerance can only be maintained if insulin resistant individuals continue to secrete greater than normal amounts of insulin. As a corollary, glucose homeostasis will decompensate when the insulin secretory response begins to fall, and the greater the decline in insulin secretion, the larger the rise in plasma glucose concentration. The net result of these changes is that plasma glucose and insulin response will be positively correlated within a population composed of glucose tolerant individuals and patients with IGT or Type 2 diabetes in the absence of significant fasting hyperglycemia. On the other hand, the relationship between plasma insulin and glucose concentration will be negatively correlated in patients with Type 2 diabetes and varying degrees of fasting hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)