Role of opioid tone in the pathophysiology of hyperinsulinemia and insulin resistance in polycystic ovarian disease

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Neltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by neltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.