Post-Prandial Liver Glucose Metabolism in PCOS

Post-Prandial Liver Glucose Metabolism in Polycystic Ovarian Syndrome (PCOS) and Understanding Standard of Care Medications

The Investigators will measure if hepatic metabolism is upregulated in obese girls with PCOS and hepatic steatosis (HS), compared to PCOS without HS and obese controls without HS.

This will be a cross-sectional study with 4 groups of youth. A 6 hour OSTT (Oral Sugar Tolerance Test) with an oral U-C13 glycerol tracer will be paired with nuclear magnetic resonance spectroscopy (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, TCA cycle and FAS pathways in girls with PCOS receiving lifestyle only, metformin or oral contraceptive treatment, and obese girls with regular menses receiving lifestyle therapy. Hepatic steatosis will be measured with MRI.

Please note that 3 study groups: PCOS on metformin, PCOS on oral contraceptive treatment, and obese girls with regular menses were not funded in the study, so no participants were enrolled in these 3 arms of the study.

Inclusion Criteria:

1. Female

2. Ages 12-21

3. Sedentary- less than 2.5 hours of moderate (jogging, swimming etc) exercise a week.

4. BMI equal or greater than the 90th percentile for age and gender

5. For PCOS groups:

   • (NIH definition) irregular menstrual cycles at least 1.5 years after menarche, and
   • either clinical evidence of hyperandogenism, or
   • elevated Testosterone (above the norms for age/tanner stage) at time of screening, or documented prior to initiation of therapy for OCP and metformin groups.

6. For PCOS groups:

   • patients un-treated or currently treated with either Metformin 1500-2000 mg a day, or
   • oral contraception (30-35 mcg ethynyl estradiol a day) for at least 6 months, with > 80% adherence confirmed via refill frequency from pharmacy.

7. For non-PCOS groups:

   • regular menstrual cycles at least 1.5 years after menarche, and
   • no clinical evidence of hyperandrogenism.

Exclusion Criteria:

1. Use of medications known to affect insulin sensitivity:

   • oral glucocorticoids within 10 days,
   • atypical antipsychotics,
   • immunosuppressant agents,
   • HIV medications.
   • Nexplanon, Depo-Provera or Mirena progesterone only contraceptives.
   • Dermal patch or vaginal ring contraception methods.
   • For controls only: metformin or oral contraception.

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.

6. Weight >325 lbs or <84 lbs.

7. Anemia, defined as Hemoglobin < 10 mg/dL

8. Diagnosed major psychiatric or developmental disorder limiting informed consent

9. Implanted metal devices that are not compatible with MRI

10. Use of blood pressure medications

11. Known liver disease other than NAFLD or AST or ALT >150 mg/mL

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