Hyperinsulinemia does not compensate for peripheral insulin resistance in obesity.
Based on previous steady-state measures of the biologic activity of insulin, it was thought that postprandial hyperinsulinemia in obesity compensated for insulin resistance. However, we recently demonstrated kinetic defects in insulin action in insulin-resistant nondiabetic obese subjects: activation of insulin-stimulated glucose disposal was slower and deactivation was faster in obese than in normal subjects. In view of these kinetic defects in peripheral insulin action and of the fact that insulin is normally secreted in a phasic manner after meals, we postulated that the hyperinsulinemia of obesity does not compensate for insulin resistance and that the abnormal kinetics of insulin action in obesity are functionally important. To test this hypothesis, oral glucose tolerance tests (OGTTs) were performed in five control (mean age, 33 +/- 2 yr) and five obese (mean age, 41 +/- 5 yr) subjects. All controls had normal glucose tolerance; two obese subjects had normal and three had impaired glucose tolerance. After the results of the OGTTs were available, euglycemic clamp studies were performed in which insulin was infused in a phasic stepped fashion to mimic the rise and fall of mean peripheral insulin levels during the OGTTs. Each subject was clamped at both the "normal" and "obese" OGTT insulin profiles. During the OGTT, glucose and insulin levels were significantly elevated in the obese subjects compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D009765:Obesity / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose