Liver and Fat Regulation in Overweight Adolescent Girls

Study Overview
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Brief Summary
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Women with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.

Detailed Description
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Hepatic glucose release will be assessed with a stable isotope glycerol tracer, lipolysis with a glycerol tracer, and hepatic de novo lipogenesis with an acetate tracer. Data will be collected fasting and after a glucose challenge. The degree of hepatic steatosis and abdominal fat partitioning will be assessed with Magnetic Resonance Imaging (MRI), and total body composition with Dual-energy X-ray absorptiometry (DEXA).

Official Title
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Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls

Conditions
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Hepatic Steatosis, Polycystic Ovarian Syndrome, Obesity

Intervention / Treatment
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* Drug: Byetta 5Mcg Pen Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 2 years post-menarche BMI percentile >90% Exclusion Criteria: Type 2 diabetes Anemia Liver disease Medications known to effect insulin sensitivity Cause of oligomenorrhea or hirsutism other than PCOS, >3 hours a week of moderate exercise.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 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: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCOS, medication naive + Byetta<br>PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. | Drug: Byetta 5Mcg Pen Injection<br>* 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola<br>* Other names: Exenatide;|
| No Intervention: Control<br>Up to 25 girls without PCOS | |
| No Intervention: PCOS medication naive<br>Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. | |
| No Intervention: PCOS on COCPs<br>Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. | |
| No Intervention: PCOS on metformin<br>Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic glucose release | Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. | Measured up to 4 months from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic phosphate concentrations | Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy | Measured up to 4 months from enrollment | 
| Rates of lipolysis | Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. | Measured up to 4 months from enrollment | 
| Hepatic Fat Fraction | Amount of fat in the liver measured by MRI and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. | Measured up to 4 months from enrollment | 
| Hepatic de novo lipogenesis | Hepatic de novo lipogenesis will be measured by with an acetate tracer. | Measured up to 4 months from enrollment |