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

2014-08-27 03:17:45 | BioPortfolio

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.

Description

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 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.

Study Design

Allocation: Randomized, Control: Active Control, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Conditions

Polycystic Ovary Syndrome

Intervention

Rosiglitazone, Acarbose

Location

Université de Sherbrooke
Sherbrooke
Quebec
Canada
J1H 5N4

Status

Recruiting

Source

Universitaire de Sherbrooke

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:17:45-0400

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Medical and Biotech [MESH] Definitions

A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.

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An inhibitor of alpha glucosidase that retards the digestion and absorption of carbohydrates in the small intestine and hence reduces the increase in blood-glucose concentrations after a carbohydrate load. It is given orally to non-insulin dependent diabetes mellitus patients where diet modification or oral hypoglycemic agents do not control their condition. (From Martindale The Extra Pharmacopoeia, 31st ed)

A rare condition of sexual ambiguity in which the individual possesses gonadal tissues of both SEXES, tissues from the OVARY and the TESTIS. There can be a testis on one side and an ovary on the other (lateral), or there may be combined ovarian and testicular tissue (ovotestes) on each side (bilateral). Most common karyotype is 46,XX. Others include 46,XY and 45,X/XY.

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