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Division of Endocrinology (R.S.F., D.E.C.), University of Washington, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108; and Stanford University School of Medicine (T.M., F.A., C.L.), Stanford, California 94305
Address all correspondence and requests for reprints to: Dr. David E. Cummings, University of Washington, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, S-111-Endo, Seattle, Washington 98108. E-mail: davidec{at}u.washington.edu.
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/m2 for the IR and IS groups, respectively. Fasting insulin concentrations were 19.5 and 7.4 µU/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.
This work was supported by NIH Grants RR-000070-40, RR-16071-01, and R01-DK-61516.
Abbreviations: BMI, Body mass index; HDL-C, high density lipoprotein cholesterol; HOMA, homeostatic model assessment; IR, insulin resistant; PCOS, polycystic ovarian syndrome; PWS, Prader-Willi syndrome; SSPG, steady state plasma glucose.
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