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The Relative Contributions of Hepatic and Peripheral Tissues to Insulin Resistance in Hyperandrogenic Women^*

A. N. PEIRIS, E. J. AIMAN, W. D. DRUCKER and A. H. KISSEBAH

Clinical Research Center and the Departments of Medicine (A.N.P., W.D.D., A.H.K.) and Obstetrics and Gynecobgy (E.J.A.), Medical College of Wisconsin Milwaukee, Wisconsin 53226

Address all correspondence and requests for reprints to: Dr. A. N. Peiris, Room 5112, Clinical Research Center, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.

Insulin resistance is associated with hyperandrogenic states. To determine the mechanisms by which androgen excess can affect insulin action, we studied insulin sensitivity in five nonobese hyperandrogenic women and six normal women. After oral glucose administration, the hyperandrogenic women had higher serum insulin concentrations than the normal women (P = 0.05). The mean cumulative peripheral serum insulin response in the hyperandrogenic women [79.6 ± 30.8 (±SD) nmol/L · 300 min] was significantly greater than that in the normal women (46.6 ± 15.1 nmol/L · 300 min; P < 0.05). In thebasal state and during hyperinsulinemic (20 mU/min · m²) euglycemic clamp studies serum insulin levels were similar in the two groups. Basal and insulin-mediated suppressions of hepatic glucose production determined from [3-³H]glucose specific activity were similar in the two groups. Peripheral glucose utilization was markedly diminished in the hyperandrogenic women compared to that in the normal women (27.8 ± 6.7 vs 48.9 ± 12.8 µmol/min · kg fat-free mass; P < 0.01). We conclude that the insulin resistance in nonobese hyperandrogenic women is due to peripheral, but not hepatic, resistance to the action of insulin. This marked peripheral insulin resistance may result from the effects of hyperandrogenemia on skeletal muscle fiber morphology and metabolism.

^* This work was supported in part by General Clinical Research Center Grant RR-00058 and NIH Grant HL-34989.

Recipient of a Clinical Associate Physician Award from the National Institutes of Health.

Received August 12, 1988.

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