title: Insulin resistance: a chicken that has come to roost.
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 (increases I). However, the ability of increases I to prevent decompensation of glucose tolerance is a mixed blessing, and the combination of I resistance and increases 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 increases 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.
authors.affiliation: Stanford University School of Medicine, California 93405, USA. greaven@shaman.com
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D003327:Coronary Disease / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005342:Fibrinolysis; D005838:Genotype; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D014527:Uric Acid / Q000097:blood
chemical_list: D014527:Uric Acid