Clinical Trial: Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Role of Insulin Action and Free Fatty Acids in Hyperandrogenism and Role of Metabolism of Inositols in Insulin Resistance of Women With Polycystic Ovary Syndrome

Brief Summary:

The investigators hypothesis is that free fatty acids (FFA) accumulation in non fatty tissues would lead to insulin resistance and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in women having polycystic ovary syndrome following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose.

For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.


Detailed Summary:

Polycystic ovary syndrome (PCOS) is a very common but complex endocrine disorder affecting 6 to 10% of childbearing age women. To diagnose PCOS, women must display two of these three symptoms: clinical or biochemical hyperandrogenism, oligoamenorrhea, and/or echographycally confirmed polycystic ovary. Many studies have also demonstrated that PCOS women are more insulin resistant than control women when matched for body mass index (BMI). Thus, insulin resistance (IR) and secondary hyperinsulinemia would be important premises in the development of PCOS. In fact, the prevalence of type 2 diabetes (T2D) is tripled in PCOS women.

Higher free fatty acid (FFA) concentrations were also observed in the circulation of PCOS women. As FFA accumulates in liver and muscle instead of fat cells, this could be an important cause of IR according to the theory of lipotoxicity. Some indirect evidences are suggesting that FFA accumulation in androgen secreting cells (ovary and adrenal gland) could enhance their androgen production. Based on these findings, our hypothesis is that FFA accumulation in non fatty tissues would lead to IR and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in PCOS women following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose. For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic cleara
Sponsor: Jean-Patrice Baillargeon

Current Primary Outcome: Androgen hyper-responsiveness to insulin, as determined by the relationship between testosterone and insulin levels (or the ratio of free testosterone to the area under the insulin curve) during an OGTT and 24h urinary clearance of DCI in PCOS women [ Time Frame: 5 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Insulin secretion as well as insulin actions on glucose utilization, hepatic glucose production and free fatty acid supressibility in PCOS women during OGTT and 2 step insulin-glucose clamp [ Time Frame: 5 years ]
  • Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp [ Time Frame: 5 years ]


Original Secondary Outcome:

  • Insulin secretion as well as insulin actions on glucose utilization, hepatic glucose production and free fatty acid supressability in PCOS women during OGTT and 2 step insulin-glucose clamp [ Time Frame: 5 years ]
  • Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp [ Time Frame: 5 years ]


Information By: Université de Sherbrooke

Dates:
Date Received: November 24, 2009
Date Started: August 2006
Date Completion: October 2021
Last Updated: October 25, 2016
Last Verified: October 2016