(289) Intranasal Insulin Enhances Post Prandial Energy Expenditure in Obese Women with Polycystic Ovary Syndrome (PCOS).

W. Colin Duncan¹, Yuan Wang¹, Riada McCredie¹, Steve Franks², Paul A. Fowler³, Roland H. Stimson⁴, Michael T. Rae⁵, Katarzyna J. Siemienowicz⁵.

1.     Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK

2.     Institute for Reproductive and Developmental Biology, Imperial College, London, UK

3.     Institute of Medical Sciences, University of Aberdeen, Aberdeen UK

4.     Centre for Cardiovascular Sciences, University of Edinburgh, UK

5.     School of Applied Sciences, Edinburgh Napier University, Edinburgh, UK


Abstract Text:

Obesity worsens the reproductive and metabolic consequences of polycystic ovary syndrome (PCOS). However, women with PCOS are more likely to be obese and find losing weight difficult. They have a deficit in adaptive energy expenditure when compared to weight-matched controls, with a 25% reduction in capacity for postprandial thermogenesis. In a clinically-realistic ovine model, using prenatal androgenisation, adult PCOS-like sheep were heavier than controls with the same 25% reduction in postprandial energy expenditure (PPEE). This was linked to a centrally-regulated defect in subcutaneous adipose tissue function. There was a reduction in insulin signalling in the brain and raising cerebral insulin, through administration of intranasal insulin (INI), in PCOS-like sheep improved PPEE.

We hypothesised that PPEE would be increased by intranasal insulin in a dose-dependent manner in obese women with PCOS.

After Research Ethics Committee approval, obese women with PCOS (n=12) were recruited from a fertility clinic and studied in the follicular phase. They 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 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.

With 40iu INI participants with PCOS had significantly greater PPEE than with saline placebo, measured as a change in PPEE over time per kg of body fat (P< 0.05). Within the subset group 80iu INI 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). INI had no adverse effects on blood glucose concentrations, pulse or blood pressure.

These results suggest proof of concept that INI can improve PPEE in obese women with PCOS and provide additional safety data for the use of INI. 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.