Endocrine Abstracts

JOINT2381

Polycystic ovary syndrome (PCOS) is a lifelong condition associated with reproductive and metabolic consequences. Obesity worsens PCOS and women with PCOS are more likely to be obese and find weight loss difficult. Women with PCOS have a reduced adaptive thermogenesis response to food meaning they don’t burn off as many calories after eating. Previous studies conducted in a clinically realistic large animal model highlighted that this is due to a centrally-regulated defect in subcutaneous adipose tissue function. These studies have also suggested intranasal insulin (INI) as a novel therapeutic strategy with the hypothesis that it could help obese women with PCOS to regulate their metabolism and lose weight. This research was conducted as part of a single site basic experimental study looking at the effect of INI on postprandial energy expenditure (PPEE) in obese women with and without PCOS. Obese women with PCOS (n=12), and obese controls without PCOS (n=12) were fed a standard meal on two occasions with either intranasal saline placebo or 40iu INI in a random and blinded manner. A subset of PCOS patients (n=6) also underwent a third linked visit with 80iu INI to determine if there was a dose-response. The effect of INI on PPEE was assessed by indirect calorimetry. Area under the curve (AUC) of PPEE was used for statistical analysis. With 40iu INI participants with PCOS had significantly greater postprandial energy (AUC 1580±166) expenditure than with saline placebo (AUC 1079±227), measured as a change in PPEE over time per kg of body fat (P<0.05). Within the subset group 80iu INI (AUC 1972±94) also caused a significant increase in PPEE vs saline placebo (P<0.01). There was a dose-response with 80iu INI increasing PPEE more than 40iu INI (P<0.05). In obese control women without PCOS 40iu INI (AUC 1314±154) had no effect in PPEE when compared to control (AUC 1393±173). There were no adverse effects on blood glucose concentrations. These results suggest proof of concept and provide additional safety data for INI in the improvement of PPEE in obese women with PCOS. There is still an unmet clinical need for accessible and cost-effective weight management treatment for patients with PCOS and this strategy warrants further investigation with proof of efficacy studies.