Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls

Ghrelin, an orexigenic hormone that may play a role in body weight regulation, is reduced in states of obesity. Because obesity is associated with insulin resistance and compensatory hyperinsulinemia, we determined whether these metabolic characteristics were independently associated with suppressed ghrelin concentrations. To investigate this hypothesis, using steady-state plasma glucose concentrations, we identified 20 insulin-resistant (IR) and 20 insulin-sensitive (IS) individuals who were equally obese. The mean body mass indexes were 32.5+/-0.4 and 32.0+/-0.4 kg/m(2) for the IR and IS groups, respectively. Fasting insulin concentrations were 19.5 and 7.4 muU/ml (P<0.001), respectively. Ghrelin concentrations were suppressed in the IR group (252 +/- 19 pg/ml) relative to the IS group (412 +/- 35 pg/ml; P<0.001). Ghrelin correlated inversely with both insulin resistance (r=-0.64; P<0.001) and fasting insulin concentration (r=-0.58; P<0.001). Multivariate analysis confirmed that both insulin resistance and hyperinsulinemia independently predicted low ghrelin concentrations. Our results demonstrate that in obese individuals, insulin resistance and hyperinsulinemia are inversely associated with ghrelin concentrations. Thus, insulin resistance or related metabolic abnormalities may constitute part of a feedback mechanism by which body weight is regulated in humans.