Incretin Effect in PCOS Women

Study Overview
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Brief Summary
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This study investigates the incretin effect in women with polycystic ovary syndrome (PCOS) before and after removal of their insulin resistance by metformin. The investigators' hypothesis is that insulin resistant women with PCOS have a reduced incretin effect and elevated glucagon responses as measured by a 75-g oral glucose tolerance test and isoglycemic i.v. glucose infusion. The investigators hypothesise that both can be improved when their insulin resistance is removed.

Official Title
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Inkretineffekten Hos Patienter Med Polycystisk Ovariesyndrom før og Efter Behandling af Insulinresistens (Incretin Effect in Patients With Polycystic Ovary Syndrome Before and After Treatment of Insulin Resistance)

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria PCOS-women: Diagnosed with PCOS according to the Rotterdam criteria more than 18 years old BMI less than 30 kg/m2 Normal glucose tolerance and fasting plasma glucose (assessed by 75-g OGTT) Negative GAD65 and islet cell autoantibodies Insulin resistant according to HOMA-IR informed consent Inclusion Criteria healthy women: more than 18 years old BMI less than 30 kg/m2 Normal glucose tolerance and fasting plasma glucose (assessed by 75-g OGTT) Negative GAD65 and islet cell autoantibodies informed consent regular menstrual cycle (28-35 days) Plasma androgen levels within reference levels Exclusion Criteria PCOS and healthy women: First or second degree relatives with diabetes pregnancy or breast feeding treatment with medication which influences the glucose metabolism (incl hormonal contraception) Congenital diseases which cause hyperandrogenism and irregular bleeding Known adrenal hyperplasia Known hyperprolaktinemia Alcohol consumption of more than 20 grams a day Hemoglobin less than 7.8 %

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin-Placebo<br>Metformin, 2x 2 tablets a day, 500 mg tablets for 12 weeks, 6 weeks wash-out, 12 weeks placebo | Drug: Metformin<br>* Metformin, 2x 2 tablets a day, 500 mg tablets<br>* Other names: 657-24-9;Drug: Placebo<br>* Placebo (to metformin)<br>|
| Placebo Comparator: Placebo-metformin<br>Placebo tablets, 2x 2 tablets per day for 12 weeks, 6 weeks wash-out, 12 weeks metformin, 2x 2 tablets per day, 500 mg per tablet | Drug: Metformin<br>* Metformin, 2x 2 tablets a day, 500 mg tablets<br>* Other names: 657-24-9;Drug: Placebo<br>* Placebo (to metformin)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in incretin effect from baseline and until after removal of insulin resistance | The incretin effect will be assessed from the insulin secretion during af 75 g OGTT and IIGI at baseline and after 12 weeks' treatment with placebo and metformin | baseline and 12 weeks' treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon response | Glucagon responses (plasma concentrations) will be assessed during the 75-g OGTTs | 0, 12 and 30 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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incretin effect, PCOS, insulin resistance, OGTT, IIGI