Insulin and the Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 2
- 主要终点
- Insulin sensitivity (Change from baseline to 8 weeks)
研究概览
简要总结
The polycystic ovary syndrome is the leading cause of female infertility in the United States. The disorder affects approximately 6-10% of women of reproductive age. It is widely accepted that "insulin resistance" may be responsible for the infertility of this syndrome. Women are insulin resistant when their bodies do not respond to insulin's action to handle sugar as they normally should. Because of this insulin resistance, women with the polycystic ovary syndrome are also at high risk for developing type 2 diabetes. We have previously shown that D-chiro-inositol (DCI), a substance naturally found in our body that helps insulin's action, is lacking in women with the polycystic ovary syndrome. Not having enough DCI may lead to insulin resistance. The purpose of this study is to determine if weight loss helps to replenish the body with DCI and help to promote insulin's action.
详细描述
Insulin resistance is present in women with PCOS. Women with PCOS are at high risk for developing type 2 diabetes, presumably due to the insulin resistance that accompanies the syndrome. Some actions of insulin may be effected by putative inositolphosphoglycan (IPG) mediators of insulin action, and evidence suggests that a deficiency in a specific D-chiro-inositol (DCI)-containing IPG may contribute to insulin resistance in individuals with impaired glucose tolerance or type 2 diabetes mellitus. A deficiency in DCI may also contribute to the insulin resistance in women with PCOS. In PCOS, three separate studies have shown that administration of DCI, the precursor to DCI-IPG, to women with PCOS improved glucose intolerance while reducing circulating insulin, improved ovulatory function, and decreased serum androgens. Serum triglycerides, HDL cholesterol and blood pressure improved in some of the studies as well. Collectively, these findings strongly suggest that administration of DCI improved insulin sensitivity in women with PCOS, and that a deficiency in DCI may contribute to the insulin resistance of this disorder.
Previous studies of our group demonstrated that women with PCOS, when compared to normal women, had a (i) greater than 5-fold increase in the renal clearance of DCI, (ii) 50% reduction in the circulating concentration of DCI, and (iii) decreased insulin-stimulated release of DCI-IPG during an oral glucose tolerance test (OGTT). Moreover, insulin sensitivity (as determined by frequently sampled intravenous glucose tolerance test [FSIVGTT]) correlated inversely with renal clearance of DCI. In addition, it appears that obesity needs to be present for the abnormality in renal clearance of DCI to be present in PCOS, and obesity does not seem to have an effect in DCI renal clearance in normal women.
Our hypothesis is that obesity modulates the renal clearance of DCI in women with PCOS, but not in normal women. A corollary of this hypothesis is that an increased urinary DCI clearance leads to a reduction in circulating DCI and insulin-stimulated DCI-IPG release, and aggravates insulin resistance in women with PCOS. To test our hypothesis, we propose to study the following specific aims:
Specific Aims:
Specific Aim 1: Determine if DCI renal clearance in obese women with PCOS is increased compared to age- and weight-matched, obese normal women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Obese (≥ 30 kg/m2) premenopausal women with PCOS and normal women between 18-40 years of age.
- •PCOS women only:
- •oligomenorrhea (<= 8 menstrual periods annually),
- •biochemical hyperandrogenemia (elevated total or free testosterone),
- •normal thyroid function tests and serum prolactin, and
- •exclusion of 21alpha-hydroxylase deficiency by a fasting 17alpha-hydroxyprogesterone <200 ng/dl.
- •Normal women only:
- •regular monthly menses, and
- •normal serum total and free testosterone.
- •All women:
- •acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis),
- •have not been dieting in the 3 months prior to study enrollment,
- •signed, witnessed informed consent,
- •ability to comply with study requirements.
排除标准
- •Diabetes mellitus by fasting glucose or OGTT, or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
- •Documented or suspected recent (within one year) history of drug abuse or alcoholism.
- •Ingestion of any investigational drug within 3 months prior to study onset.
- •Pregnancy as documented by urine hCG.
- •PCOS women only: Change in PCOS medication regimen (oral contraceptives, spironolactone, insulin sensitizers) within 3 months prior to the start of the study.
- •Normal women only:
- •history of gestational diabetes,
- •positive family history for first-degree relative with diabetes,
- •disorders linked to insulin resistance (hypertension or dyslipidemia),
- •Use of oral or other systemic contraceptives, or spironolactone within 3 months prior to the start of the study,
- •Use of medications (including OTC drugs) known to affect insulin sensitivity such as metformin, rosiglitazone, pioglitazone, niacin, corticosteroids, beta blockers, calcium channel blockers and thiazide diuretics within 3 months prior to the start of the study.
研究组 & 干预措施
Control
Non-PCOS women receiving weight loss intervention
干预措施: Weight loss (Behavioral)
PCOS
PCOS women receiving weight loss intervention
干预措施: Weight loss (Behavioral)
结局指标
主要结局
Insulin sensitivity (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
Changes of Serum D-Chiro-Inositol (DCI) concentrations (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
Changes of DCI renal clearance (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
Changes of AUC insulin during OGTT (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
AUC of bioactive DCI-IPG during OGTT (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
Ratio of AUC DCI-IPG to AUC insulin during OGTT (Change from baseline to 8 weeks)
时间窗: Baseline to 8 weeks
次要结局
- Weight loss (Change from baseline to 8 weeks)(Baseline to 8 weeks)
- Serum Myo-Inositol (Myo) concentrations (Change from baseline to 8 weeks)(Baseline to 8 weeks)
- MYO bioactivity (Change from baseline to 8 weeks)(Baseline to 8 weeks)
- Serum inflammatory and cardiovascular markers (Change from baseline to 8 weeks)(Baseline to 8 weeks)