The counterregulatory response to hypoglycaemia in women with the polycystic ovary syndrome

OBJECTIVE The pathogenetic mechanisms behind insulin resistance in polycystic ovary syndrome (PCOS) are far from fully elucidated. Aberrant counterregulatory responses to hypoglycaemia have been reported in patients with insulin resistance, and recent reports suggest that plasma glucose may be regulated at lower levels in women with PCOS. In this study we investigated the complete hormonal counterregulatory response to hypoglycaemia in women with PCOS. DESIGN Prospective cross-sectional study. PATIENTS Eight obese (BMI greater than or equal to 25) and 10 non-obese (BMI < 25) women with PCOS, diagnosed by means of ultrasonography and clinical signs of chronic anovulation. Eight obese and 9 non-obese controls. MEASUREMENTS Hypoglycaemia was induced by an intravenous bolus of soluble insulin (0.15 IU/kg body weight). The counterregulatory responses of cortisol, GH, catecholamines, glucagon, chromogranin A (CGA), and neuropeptide Y (NPY) were studied together with symptoms of hypoglycaemia. RESULTS The obese women with PCOS had a more pronounced truncal-abdominal body fat distribution (waist hip ratio, WHR) and were hyperinsulinaemic, compared with the obese controls. All the women exhibited blood glucose levels (<2 mmol/l) well below the threshold for the hormonal counterregulatory response and for the appearance of clinical symptoms. The non-obese women with PCOS showed a greater increase in serum concentrations of GH than the lean controls. The obese women with PCOS exhibited blunted responses of noradrenaline and NPY, but similar increases of adrenaline and CGA, compared with the obese controls. They also showed a lower symptom score during hypoglycaemia. The response of noradrenaline to hypoglycaemia correlated inversely with fasting insulin levels in the women with PCOS. Among all the obese women (PCOS and controls pooled) basal levels of noradrenaline correlated inversely with the WHR. CONCLUSIONS All the women with PCOS, independent of BMI, body fat distribution and insulin levels, showed preserved counterregulatory responses to hypoglycaemia. The reduced plasma levels of noradrenaline and the lower perception of hypoglycaemic symptoms in the obese women with PCOS could both reflect a lower activation of the sympathetic nervous system. This aberration seems related to truncal-abdominal obesity and hyperinsulinaemia. The finding of an increased response of GH in the lean women with PCOS could support previous suggestions of an altered activity of the GH/IGF-I system in these women.