(Circulation. 1996;93:1780-1783.)
© 1996 American Heart Association, Inc.
Articles |
Insulin Resistance, Its Consequences, and Coronary Heart Disease
Must We Choose One Culprit?
From the Department of Medicine, Stanford University School of Medicine, Stanford, Calif, and Shaman Pharmaceuticals, Inc, South San Francisco, Calif.
Key Words: Editorials • insulin • atherosclerosis • coronary disease
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Introduction |
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Approximately 25 years ago, our research group1 2 used quantitative methods to show that resistance to insulin-mediated glucose disposal was present in patients with either impaired glucose tolerance or NIDDM. These initial observations have been confirmed on multiple occasions since then, and there is now a large body of evidence that shows that this defect is present in the vast majority of glucose-intolerant individuals.3 4 5 6 7 8 In addition, several reports9 10 11 demonstrated that first-degree relatives of patients with NIDDM are also relatively insulin resistant compared with well-matched volunteers without a family history of NIDDM. Finally, prospective studies12 13 14 15 16 have identified insulin resistance and/or compensatory hyperinsulinemia as the initial defect in the development of NIDDM. Thus, the central role of insulin resistance in the pathogenesis and clinical course of patients with NIDDM has been well established. Of greater relevance to the IRAS study of "Insulin Sensitivity and Atherosclerosis" published in this issue of Circulation17 is recent awareness that the ability of insulin to mediate glucose disposal can differ by as much as 10-fold in subjects with normal glucose tolerance.18 19 Because the degree of insulin resistance in a substantial portion of these persons approaches that seen in patients with impaired glucose tolerance or NIDDM, it is assumed that they are able to secrete enough insulin to overcome the insulin resistance and maintain normal glucose tolerance.
Unfortunately, the philanthropic response on the part of the pancreatic
ß-cell is not without cost, and in 1988,20 it was
emphasized that these individuals were at increased risk to have higher
plasma
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