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Assessment of Insulin Sensitivity from Measurements in the Fasting State and during an Oral Glucose Tolerance Test in Polycystic Ovary Syndrome and Menopausal Patients

Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore (M.C., F.L., F.C., S.M.), 00168 Rome, Italy; Laboratorio di Biomatematica, Consiglio Nazionale delle Ricerche Istituto di Analisi dei Sistemi ed Informatica (S.P., A.D.G.), Rome, Italy; and OASI Institute for Research (A.L.), Troina, Italy

Address all correspondence and requests for reprints to: Dr. Antonio Lanzone, Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, L.go A. Gemelli 8, 00168 Rome, Italy. E-mail: alanzone{at}rm.unicatt.it.

Background: Polycystic ovary syndrome (PCOS) and menopausal subjects are characterized by an increased cardiovascular and type 2 diabetes mellitus risk, at least partially related to insulin disturbances. The evaluation of insulin resistance in these patients could be useful as primary prevention. The aim of the study was to verify the validity of several indexes of insulin sensitivity in PCOS and menopausal subjects by comparing the data obtained by these indexes to those of euglycemic-hyperinsulinemic clamp studies.

Methods: One hundred PCOS and 110 menopausal subjects were analyzed; all subjects underwent an oral glucose tolerance test (75 g) and euglycemic-hyperinsulinemic clamp study. Seven PCOS patients and 13 menopausal subjects had impaired glucose tolerance or type 2 diabetes mellitus and were excluded from the study. After analysis of correlation coefficients between the evaluated indexes and the clamp studies, the sensitivity and specificity of different cut-off values for each parameter were analyzed by receiver operating characteristic (ROC) curves.

Results: The best correlation coefficients with clamp studies were obtained with the Avignon insulin sensitivity index (SiM) (R_s = 0.7812) in PCOS patients and the Matsuda and De Fronzo index (R_s = 0.6178) in menopausal patients.

The best predictive index of insulin resistance in PCOS was a Avignon insulin sensitivity basal index (SibB) value of 62 or less (78% sensitivity, 95% specificity) and an insulin area under the curve (AUC) of 7,000 µIU/ml or more (50,225 pmol/liter) x 120 min (83% sensitivity, 90% specificity). In the menopausal population, the best predictive performance was obtained by an insulin AUC of 10,000 µIU/ml or more (71,750 pmol/liter) x 240 min (70% sensitivity, 88% specificity).

Conclusions: The presence of high correlation coefficients does not necessarily mean that the indexes of insulin resistance have an optimal predictive performance; this is probably due to the presence of many borderline values. The simple evaluation of insulin AUC seems to effectively replace the euglycemic-hyperinsulinemic clamp in routine clinical practice, allowing results superimposable to those obtained by minimal model analysis.

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