Pathophysiology of insulin resistance in human disease

GM Reaven - Physiological reviews, 1995 - journals.physiology.org
GM Reaven
Physiological reviews, 1995journals.physiology.org
The ability of insulin to stimulate glucose uptake varies widely from person to person, and
these differences, as well as how the individual attempts to compensate for them, are of
fundamental importance in the development and clinical course of what are often
designated as diseases of Western civilization. Evidence is presented that non-insulin-
dependent diabetes mellitus (NIDDM) results from a failure on the part of pancreatic beta-
cells to compensate adequately for the defect in insulin action in insulin-resistant individuals …
The ability of insulin to stimulate glucose uptake varies widely from person to person, and these differences, as well as how the individual attempts to compensate for them, are of fundamental importance in the development and clinical course of what are often designated as diseases of Western civilization. Evidence is presented that non-insulin-dependent diabetes mellitus (NIDDM) results from a failure on the part of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. In addition, a coherent formulation of the physiological changes that lead from the defect in cellular insulin action to the loss in glucose homeostasis is presented. However, the ability to maintain the degree of compensatory hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin-resistant individuals does not represent an unqualified homeostatic victory. In contrast, evidence is presented supporting the view that the combination of insulin resistance and compensatory hyperinsulinemia predisposes to the development of a cluster of abnormalities, including some degree of glucose intolerance, an increase in plasma triglyceride and a decrease in high-density lipoprotein cholesterol concentrations, high blood pressure, hyperuricemia, smaller denser low-density lipoprotein particles, and higher circulating levels of plaminogen activator inhibitor 1. The cluster of changes associated with insulin resistance has been said to comprise syndrome X, and all of the manifestations of syndrome X have been shown to increase risk of coronary heart disease. Thus it is concluded that insulin resistance and its associated abnormalities are of utmost importance in the pathogenesis of NIDDM, hypertension, and coronary heart disease.
American Physiological Society