Hyperinsulinemia Does Not Compensate for Peripheral Insulin Resistance in Obesity

Abstract

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)

Fasting and postprandial levels of ghrelin, leptin and insulin in lean, obese and anorexic subjects

“…As expected, insulin levels rose after a meal in all three groups, and the greatest rise was observed in obese subjects (we noted a 4-fold increase in insulin levels) leading to hyperinsulinaemia. These findings are consistent with worldwide studies [23]. …”

Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load

“…This indicates that the hyperglycemic and hyperinsulinemic responses following an oral glucose load are not sufficient to overcome the underlying metabolic defect in obese and type 2 diabetic subjects. This result is concordant with prior reports using dynamic insulin clamps (17, 18, 33) to mimic the OGTT response, with the obvious advantage that our results reflect native in vivo responses. Our analyses suggest that neither insulin resistance nor impairments in glucose-mediated glucose disposal are overcome.…”

Is Obesity an Underlying Factor in Erectile Dysfunction?

“…Based on these results, therefore, we can presume that obesity in itself does not seem to have an independently adverse effect on erectile function, but it is at least a contributing factor mediated by the increasing risk of the patient having vascular pathology in the body and penis. It is well known that obese individuals have a greater risk of developing various metabolic and vascular alterations including non-insulin-dependent diabetes, hypertension, hyperlipidemia, and atherosclerosis [8, 9, 10]. The impact of obesity on diabetes and hyperlipoproteinemic states results primarily from its influence on insulin secretion and insulin sensitivity.…”