Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)
| Status: | Terminated |
|---|---|
| Conditions: | Ovarian Cancer, Women's Studies |
| Therapuetic Areas: | Oncology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 10/14/2017 |
| Start Date: | February 2009 |
| End Date: | August 2011 |
Determination if Indirectly Reducing Circulating Insulin by Improving Insulin Sensitivity With Pioglitazone Reduces Renal Clearance of D-chiro-inositol (DCI) Increases the Circulating Concentration of DCI and Enhances Insulin-stimulated Release of the D-chiro-inositol-containing Inositolphosphoglycan (DCI-IPG) Mediator in Obese Women With PCOS
Our hypothesis is that hyperinsulinemia increases the renal clearance of D-chiro-inositol
(DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in
circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG)
release. To assess the effects of a chronic reduction in circulating insulin on DCI
metabolism, we propose to reduce circulating insulin in obese women with PCOS by improving
insulin sensitivity with the drug pioglitazone. Pioglitazone is a thiazolidinedione that
improves peripheral insulin sensitivity, presumably by activation of the peroxisome
proliferator-activated receptor gamma (PPARγ) receptor. Administration of pioglitazone to
women with PCOS has been shown to improve insulin sensitivity, reduce insulin secretion, and
decrease both fasting and post-prandial serum insulin concentrations.
(DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in
circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG)
release. To assess the effects of a chronic reduction in circulating insulin on DCI
metabolism, we propose to reduce circulating insulin in obese women with PCOS by improving
insulin sensitivity with the drug pioglitazone. Pioglitazone is a thiazolidinedione that
improves peripheral insulin sensitivity, presumably by activation of the peroxisome
proliferator-activated receptor gamma (PPARγ) receptor. Administration of pioglitazone to
women with PCOS has been shown to improve insulin sensitivity, reduce insulin secretion, and
decrease both fasting and post-prandial serum insulin concentrations.
This protocol focuses on the hypothesis that a deficiency in a putative inositolphosphoglycan
(IPG) mediator of insulin action, namely a D-chiro-inositol-containing IPG (DCI-IPG),
contributes to the insulin resistance of some women with PCOS. Our interest in this area
stems directly from our previous studies, which demonstrated that administration of the
precursor, D-chiro-inositol (DCI), to both obese and lean women with PCOS improved glucose
intolerance while reducing circulating insulin, and simultaneously improved ovulatory
function and decreased serum androgens. These findings were recently confirmed in a
large-scale study by an independent group. The findings of these three studies suggested that
administration of DCI improved insulin sensitivity in PCOS, which then resulted in an
improved hormonal and metabolic milieu.
(IPG) mediator of insulin action, namely a D-chiro-inositol-containing IPG (DCI-IPG),
contributes to the insulin resistance of some women with PCOS. Our interest in this area
stems directly from our previous studies, which demonstrated that administration of the
precursor, D-chiro-inositol (DCI), to both obese and lean women with PCOS improved glucose
intolerance while reducing circulating insulin, and simultaneously improved ovulatory
function and decreased serum androgens. These findings were recently confirmed in a
large-scale study by an independent group. The findings of these three studies suggested that
administration of DCI improved insulin sensitivity in PCOS, which then resulted in an
improved hormonal and metabolic milieu.
Inclusion Criteria:
1. Obese (Body Mass Index or BMI greater than or equal to 30 kg/m2) women with PCOS
between 18-40 years of age:
- oligomenorrhea (less than 8 menstrual periods annually)
- biochemical hyperandrogenemia (elevated total or free testosterone)
- normal thyroid function tests and serum prolactin; AND
- exclusion of 21a-hydroxylase deficiency by a fasting 17a-hydroxyprogesterone less
than 200 ng/dl.51,
2. acceptable health on the basis of interview, medical history, physical examination,
and laboratory tests (Complete Blood Chemistry or CBC, Comprehensive Metabolic Panel
denoted SMA20, urinalysis, negative pregnancy test).
3. Signed, witnessed informed consent.
4. Ability to comply with study requirements.
Exclusion Criteria:
1. Diabetes mellitus by fasting glucose or oral glucose tolerance test (OGTT), or
clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric,
infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
2. Current use of oral contraceptives.
3. Documented or suspected recent (within one year) history of drug abuse or alcoholism.
4. Ingestion of any investigational drug within two months prior to study onset.
We found this trial at
2
sites
Avenida Panteón con Avenida Alameda, Urb. San Bernandino Avenida Panteón
Caracas,
Caracas,
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