Pathophysiology of Insulin Resistance in Human Disease.
Reaven, Gerald M.
Department of Medicine, Stanford University School of Medicine and
Geriatric Research, Education and Clinical Center, Department of Veterans
Affairs Medical Center, Palo Alto, California.
APStracts 2:0006P, 1995.
ABSTRACT
The ability of insulin to stimulate glucose uptake varies widely from person
to person, and those 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 and unqualified homestatic
victory. In contrast, evidence is presented supporting the view that the
combination of insulin resistance and compensatory hyperinsulinemia pre-
disposes to the development of a cluster of abnormalities, including some
degree of glucose intolerance, an increase in plasma triglyceride, a decrease
in high-density lipoprotein cholesterol concentration, high blood pressure,
hyperuricemia, smaller denser low-density lipoprotein particles, and higher
ciruculating 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 abnormalites are of utmost importance in the pathogenesis
of NIDDM, hypertension, and coronary heart disease.
APS Manuscript Number P-0005-5.
Article publication scheduled July 1995 Physiological Reviews.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.