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Glucose-to-Insulin Ratio Rather than Sex Hormone-Binding Globulin and Adiponectin Levels Is the Best Predictor of Insulin Resistance in Nonobese Women with Polycystic Ovary Syndrome

Centre de Recherche en Nutrition Humaine (P.-H.D., M.L.), and Fédération de Biochime de l’Hôpital Eouard Herriot (E.M., H.B.) Hospices Civils de Lyon, 69437 Lyon Cedex 08; Institut National de la Santé et de la Recherche Médical U449 (H.V., M.L.), Faculté de Médecine Laennec 69373 Lyon Cedex 08; and Fédération d’Endocrinologie de l’Hôpital de l’Antiquaille (P.C., M.P.), 69321 Lyon Cedex 05, France

Address all correspondence and requests for reprints to: Michel Pugeat, M.D., Fédération d’Endocrinologie, Hôpital Neuro-Cardiologique, Hospices Civils de Lyon, Bâtiment HGPO–59 boulevard Pinel, 69349 Lyon Cedex 03, France. E-mail: michel.pugeat{at}chu-lyon.fr.

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg·min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R² = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R² = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01).

This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.

This work was supported in part by a generous grant from Novo Industry under the auspices of the ALFEDIAM Society and from the Fondation de France (Grant no. 9002364). This work was presented in part at the 83rd Annual Meeting of The Endocrine Society, Denver, Colorado, June 2001 (Abstract OR32-5).

Abbreviations: AUC, Area under the curve; BMI, body mass index; GIR, glucose-to-insulin ratio; HDL, high-density lipoprotein; HOMA, homeostasis model of assessment; PCOS, polycystic ovary syndrome; WHR, waist-to-hip ratio.

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