Insulin Resistance: A Chicken That Has Come to Roost
Article first published online: 6 FEB 2006
Annals of the New York Academy of Sciences
How to Cite
REAVEN, G. M. (1999), Insulin Resistance: A Chicken That Has Come to Roost. Annals of the New York Academy of Sciences, 892: 45–57. doi: 10.1111/j.1749-6632.1999.tb07784.x
- Issue published online: 6 FEB 2006
- Article first published online: 6 FEB 2006
ABSTRACT: Insulin-mediated glucose disposal varies approximately 10-fold in apparently healthy human beings. Insulin (I)-resistant individuals can remain glucose tolerant if the pancreas compensates for this defect by secreting large amounts of I. Type 2 diabetes develops when I-resistant persons cannot sustain this state of compensatory hyperinsulinemia ( I). However, the ability of I to prevent decompensation of glucose tolerance is a mixed blessing, and the combination of I resistance and I predisposes such individuals to develop a series of abnormalities that increase risk of coronary heart disease (CHD). Given the health-related consequences of I resistance and I, it has been suggested that a “thrifty” genotype exists that favored evolutionary survival by enhancing I secretion and thereby promoting energy accumulation. An alternative view is that conservation of muscle mass was necessary for survival, and that muscle I resistance was the “thrifty” genotype. This latter hypothesis is more consistent with current data, and there is evidence of a genetic basis for I resistance. In either case, there is little question as to the importance of I resistance and related abnormalities in diseases of Western civilization. However, the strength of the association between I resistance and its consequences varies in magnitude, and it is necessary to emphasize that development of a clinical end-point will vary as a function of (1) degree of I resistance; (2) “closeness” of I resistance to the end-point; and (3) the ability to compensate for the effects of I resistance. I resistance is a physiological characteristic, genetically determined, that helped primitive humans to survive. It is greatly aggravated by obesity and physical inactivity, and represents a modern scourge.