Heterogeneity in β cell activity , hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome

et al., 1990), the underlying mechanisms have not been clearly 1Department of Obstetrics and Gynecology, Catholic University of defined. Hyperinsulinaemia may reflect an adaptive response Sacred Heart, Rome and 2OASI Institute for Research, Troina, Italy of β cells to the accompanying peripheral insulin resistance 3To whom correspondence should be addressed at: Department of (Dunaif et al., 1989). However, before reaching the periphery, Obstetrics and Gynecology, Catholic University of Sacred Heart, insulin must transverse the liver, where a variable extraction L.go A. Gemelli 8, 00168 Rome, Italy takes place (Polonsky and Rubenstein, 1984); this suggests The aim of this study was to evaluate the impact of reduced that an abnormal hepatic insulin metabolism may contribute peripheral insulin sensitivity, β cell hypersecretion and to hyper-insulinaemia. reduced hepatic insulin clearance in the hyper-insulinaemia Obesity is a well recognized cause of hyper-insulinaemia of lean and obese PCOS patients. A total of 35 women and insulin resistance in normal subjects (Campbell and Gerivh, with polycystic ovary syndrome (PCOS) and 10 lean normo1990). Thus there is controversy as to whether insulin resistance ovulatory controls underwent an oral glucose tolerance results from PCOS itself or from the obesity which is frequently test and an euglycaemic–hyper-insulinaemic clamp study. associated with the syndrome. Although recent reports of a PCOS patients were classified into four groups according similar peripheral insulin sensitivity between PCOS patients to their BMI and insulin secretion (normo-lean; normoand control subjects (Despres t al., 1989; Ovesenet al., 1993) obese; hyper-lean; hyper-obese), and results were compared have suggested that insulin resistance is not necessarily a between groups and with the controls. All the PCOS groups primary feature of this syndrome, there seems to be little doubt showed significantly higher insulin secretion than controls; that the majority of obese PCOS patients are insulin resistant there were no differences in insulin response to glucose load (Dunaif et al., 1989). between lean and obese normoand hyper-insulinaemic Moreover, an exaggerated insulin secretion after an oral patients. Secretion of c-peptide was greater in PCOS groups glucose tolerance test was exhibited by ~70% of obese, but than controls. All the hyper-insulinaemic PCOS patients also by 20–40% of lean, PCOS subjects (Lanzone et al., had lower values of hepatic insulin clearance, independent 1990), suggesting that hyper-insulinaemia may affect the of BMI, when compared either with controls (P , 0.001) PCOS population independently from an accompanying insulin or with PCOS normo-insulinaemic women (P , 0.01). resistance as well as from obesity. Normoand hyper-insulinaemic obese patients had similar The aim of our study was to evaluate the impact of reduced total body glucose utilization (M value), which was lower peripheral insulin sensitivity, β cell hypersecretion and reduced than in lean PCOS subjects and controls. Our results hepatic insulin clearance in determining the hyper-insulinaemia suggest that evaluation of insulin resistance alone does not of lean and obese PCOS patients. fully characterize the PCOS population; differences in liver