Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

Hepatic Fat Fraction measured after completing placebo and amino acid therapy measured with 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

Time frame: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: adolescent girls with PCOS

Targeted amino acid metabolomics will be performed after each intervention and the levels of these 4 amino acids will be reported after each intervention.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Apnea Hypopnea Index (AHI) will be measured using WatchPAT after each intervention. In children and adolescents the scale that will be used is AHI\>5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea. The AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep. Normal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.

Targeted bile acid metabolomics will be performed after each intervention to measure levels of sphingosine-1-phospate

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids (FFAs) during the oral glucose tolerance test.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: This measure was completed by 22 participants in the placebo phase of the study and 20 in the EAA phase of the study

Mitochondrial function will be assessed via change in direct hepatic carbon flux in newly synthesized triglycerides (TGs) using an oral sugar tolerance test with an oral UC13 glycerol tracer after each intervention. Data from 180 minutes post-tracer drink is shown below. A higher direct percent means less indirect futile cycling through the TCA cycle.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

hepatic phosphate profile via 31 Phosphorus MR spectroscopy after each intervention Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy after each intervention. The Total phosphate (TP) concentration will be reported after each intervention and the ratio of the following phosphate metabolites will be reported over the total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: We were only able to analyze 18 participants p-31 spectroscopy due to the quality of the spectra.

Targeted lipid metabolomics will be performed after each intervention to measure 16n1 lipids after completing 4 weeks of essential amino acid therapy and 4 weeks of placebo.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

The rate of overnight de novo lipogenesis will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction measured after 4 weeks of placebo and after 4 weeks of EAA intervention.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: We were only able to obtain results for this outcome for 19 participants in the study.

Sleep duration will be assessed completing placebo and essential amino acid therapy using home actigraphy. Change in sleep duration reported in minutes.

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.

Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model using 4 hour glucose and insulin data during the OGTT after each phase of the study (placebo vs EAA).

Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Only 20 participants analyzed because the OMM model cannot be run if we have missing insulin or glucose values during the oral sugar tolerance test.