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Relationship of Androgenic Activity to Splanchnic Insulin Metabolism and Peripheral Glucose Utilization in Premenopausal Women^*

Department of Medicine and Clinical Research Center, Medical College of Wisconsin, and the Milwaukee School of Engineering Milwaukee, Wisconsin 53226

Address request for reprints to: Dr. Ahmed H. Kissebah, Clinical Research Center, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.

The importance of androgenic activity in mediating the effects of obesity and body fat topography on splanchnic insulin metabolism and peripheral insulin sensitivity was studied in 19 nonhirsute premenopausal women with a wide range of ideal body weight [percent ideal body weight (% IBW), 78–202%] and body fat distribution pattern [waist to hip girth ratio (WHR), 0.67–0.91]. Turnover kinetics of peripheral plasma C-peptide and insulin were measured, and estimates of pancreatic insulin production (PIP) and the hepatic extraction fraction (HEF) were calculated. The peripheral insulin sensitivity index (M/I) was determined during an euglycemic insulin clamp study. Androgenic activity was assessed by estimating the plasma level of sex hormone-binding globulin (SHBG) and percentage of free testosterone (% FT).

After iv glucose stimulation, PIP ranged from 40–254 mU/min·m² and correlated highly with % IBW (r = 0.78; P < 0.01). Insulin HEF ranged from 5–69% of the pancreatic production and was inversely proportional to WHR (r = –0.60; P < 0.01). Increasing WHR also correlated with the diminution in M/I (r = –0.47; P < 0.05), which, in turn, correlated with the decline in the HEF of insulin (r = 0.60; P < 0.01). Since PIP, HEF, and M/I correlated with SHBG and % FT, and since the degree of androgenic activity correlated with % IBW and WHR, partial regression analysis was performed. After adjusting for the effects of SHBG and % FT, the relationship between % IBW and PIP remained unaltered, whereas the correlation between WHR and HEF or M/I and their relationship to each other were either markedly reduced or became insignificant.

Thus, in premenopausal women, the increase in pancreatic insulin production with increasing weight is independent of the degree of androgenic activity. On the other hand, the decline in hepatic insulin extraction and diminution in peripheral insulin sensitivity with upper body fat localization are in part mediated by increased androgenic activity. This association may account for the pronounced hyperinsulinemia and insulin resistance characteristic of this form of obesity.

^* Presented in part at the American Diabetes Association and North American Association for the Study of Obesity Joint Conference on Obesity and Noninsulin Dependent Diabetes Mellitus, Toronto, Ontario, Canada, 1985. This work was supported by GCRC Grant RR-00058 and NIH Grant HL-32060.

Received May 20, 1986.

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