Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

The Investigators will measure hepatic glucose and fat metabolism in obese girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) after taking 4 weeks of an essential amino acid (EAA) supplement or placebo and test whether the EAA supplement can improve hepatic glucose metabolism in these girls.

Girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) will complete a 12 week double-blinded placebo controlled cross-over study with 4 weeks each of an essential amino acid (EAA) supplement and placebo, and will complete metabolic studies after each intervention. There will be a 4 week wash out period in-between. The metabolic tests after each intervention (EAA/placebo) will include an oral sugar tolerance test (OSTT) and an oral U-C13 glycerol tracer that is paired with Nuclear Magnetic Resonance (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, tricarboxylic acid (TCA) cycle and fatty acid synthesis pathways in girls with PCOS and HS. Hepatic steatosis will be measured with magnetic resonance Imaging (MRI) and hepatic phosphate concentrations with magnetic resonance (MR) spectroscopy.

Inclusion Criteria:

1. Females
2. Ages 12-21
3. Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
4. BMI equal or greater than the 90th percentile for age and gender
5. PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >24 months post-menarche and clinical or biochemical hypertestosteronemia)
6. HS per FibroScan ultrasound, with CAP score of >225 (will be measured at screening visit)

Exclusion Criteria:

1. Use of medications known to affect insulin sensitivity: metformin, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception. Dermal patch or vaginal ring contraception methods.
2. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
3. Severe illness requiring hospitalization within 60 days
4. Diabetes, defined as Hemoglobin A1C > 6.4%
5. BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs or <84 lbs.
6. Anemia, defined as Hemoglobin < 11 mg/dL
7. Diagnosed major psychiatric or developmental disorder limiting informed consent
8. Implanted metal devices that are not compatible with MRI
9. Use of blood pressure medications
10. Known liver disease other than NAFLD or AST or ALT >125 IU/L