Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00436865
Status:
COMPLETED
Last Update Posted:
2018-03-30
First Post:
2007-02-15
Brief Title:
Insulin and the Polycystic Ovary Syndrome--Weight Reduction Study
Sponsor:
Virginia Commonwealth University
Organization:
Virginia Commonwealth University
Study Overview
Official Title:
Insulin and the Polycystic Ovary Syndrome
Status:
COMPLETED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 insulins 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 insulins 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 insulins action
Detailed Description:
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
In this aim we will determine if obese women with PCOS have i increased renal clearance of DCI ii decreased circulating levels of DCI and iii decreased DCI-IPG release in blood during an OGTT as compared to age- and BMI-matched obese normal women
Specific Aim 2 Determine if weight loss reduces DCI renal clearance in obese women with PCOS but not in age- and weight-matched obese normal women
This aim determines if weight loss reverses the abnormalities in DCI handling in PCOS The effects of weight loss on i renal clearance of DCI ii circulating levels of DCI and iii DCI-IPG release in blood during an OGTT will be compared between obese women with PCOS and age- and BMI-matched obese normal women
Specific Aim 3 Determine if a change reduction in DCI renal clearance as a result of weight loss is correlated with a change improvement in insulin sensitivity in obese women with PCOS that is independent of weight loss itself
In our Preliminary Studies we have determined that insulin sensitivity has a significant inverse relationship with urinary DCI clearance In this aim we will determine if decreasing DCI renal clearance by weight loss in obese women with PCOS will improve insulin sensitivity independent of the degree of weight loss via statistical adjustment with the degree of weight loss as a covariate
Specific Aim 4 Determine if an equivalent degree of weight loss in obese women with and without PCOS is associated with i a greater reduction in DCI renal clearance and ii a greater improvement in insulin sensitivity in the PCOS women compared to the normal women
To further demonstrate whether improvement in insulin sensitivity as a result of an improvement in DCI handling is independent of weight loss itself women will be stratified by the degree of weight loss For each degree of weight loss we will determine if obese women with PCOS have i a greater reduction of renal clearance of DCI and ii a greater improvement in insulin sensitivity as a result of weight reduction as compared to weight-matched obese normal women
If our proposed studies confirm a role for obesity in modulating DCI handling in PCOS they will substantially enhance our understanding of the pathogenesis of PCOS and are likely to provide insights into novel treatment strategies directed specifically at the IPG system and normalization of its function
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
In this aim we will determine if obese women with PCOS have i increased renal clearance of DCI ii decreased circulating levels of DCI and iii decreased DCI-IPG release in blood during an OGTT as compared to age- and BMI-matched obese normal women
Specific Aim 2 Determine if weight loss reduces DCI renal clearance in obese women with PCOS but not in age- and weight-matched obese normal women
This aim determines if weight loss reverses the abnormalities in DCI handling in PCOS The effects of weight loss on i renal clearance of DCI ii circulating levels of DCI and iii DCI-IPG release in blood during an OGTT will be compared between obese women with PCOS and age- and BMI-matched obese normal women
Specific Aim 3 Determine if a change reduction in DCI renal clearance as a result of weight loss is correlated with a change improvement in insulin sensitivity in obese women with PCOS that is independent of weight loss itself
In our Preliminary Studies we have determined that insulin sensitivity has a significant inverse relationship with urinary DCI clearance In this aim we will determine if decreasing DCI renal clearance by weight loss in obese women with PCOS will improve insulin sensitivity independent of the degree of weight loss via statistical adjustment with the degree of weight loss as a covariate
Specific Aim 4 Determine if an equivalent degree of weight loss in obese women with and without PCOS is associated with i a greater reduction in DCI renal clearance and ii a greater improvement in insulin sensitivity in the PCOS women compared to the normal women
To further demonstrate whether improvement in insulin sensitivity as a result of an improvement in DCI handling is independent of weight loss itself women will be stratified by the degree of weight loss For each degree of weight loss we will determine if obese women with PCOS have i a greater reduction of renal clearance of DCI and ii a greater improvement in insulin sensitivity as a result of weight reduction as compared to weight-matched obese normal women
If our proposed studies confirm a role for obesity in modulating DCI handling in PCOS they will substantially enhance our understanding of the pathogenesis of PCOS and are likely to provide insights into novel treatment strategies directed specifically at the IPG system and normalization of its function
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| K23HD049454-01A2 | NIH | None | httpsreporternihgovquickSearchK23HD049454-01A2 |