Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Digestive System Diseases

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Syndrome

Obesity

Fatty Liver

Polycystic Ovary Syndrome

Liver Diseases

Gastrointestinal Diseases

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Visceral Steatosis

Hypoglycemic Agents

All Drugs and Chemicals

Hematinics

Reproductive Control Agents

Metformin

Liver Extracts

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Contraceptive Agents

Contraceptives, Oral

PCOS per NIH criteria. Obese Lifestyle treatment only.

PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.

PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months.

Obese Regular menses at least 18 months post-menarche Females only

oral glucose tolerance test

MRI of liver

Melanie Cree-Green, MD, PhD

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.

Post-Prandial Liver Glucose Metabolism in PCOS

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

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.

Percent indirect glucose at 360 minutes following an oral sugar tolerance test (OGTT) with an isotope labeled oral glycerol tracer.

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.

Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.

Apnea Hypopnea Index (AHI) will be measured using WatchPAT. 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

31 phosphorus spectroscopy will be utilized to measure hepatic Phosphodiesterase (PDE)/Total phosphate concentration. This is measured in the MRI using a phosphorus coil.

University of Colorado, Denver

Adverse events only reported for the untreated PCOS group, since no participants were enrolled in the other groups.

PCOS per NIH criteria. Obese Lifestyle treatment only.

oral glucose tolerance test: 6 hours OGTT

MRI of liver: MRI of the liver and use of DIXON method

Untreated PCOS

PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.

oral glucose tolerance test: 6 hours OGTT

MRI of liver: MRI of the liver and use of DIXON method

Metformin PCOS-(Study Arm Not Funded)

PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months.

oral glucose tolerance test: 6 hours OGTT

MRI of liver: MRI of the liver and use of DIXON method

Oral Contraceptive PCOS-(Study Arm Not Funded)

Obese Regular menses at least 18 months post-menarche Females only

oral glucose tolerance test: 6 hours OGTT

MRI of liver: MRI of the liver and use of DIXON method

Obese Control Group-(Study Arm Not Funded)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Only participants enrolled in the untreated PCOS group. No participants were enrolled in the other arms of the study due to funding.

Due to the Covid-19 outbreak, and lack of funding we were unable to enroll the participants in the metformin arm, oral contraceptive arm, and the obese control group. Only enrolled participants in untreated PCOS group.

Melanie Cree-Green, PI

Hepatic Fat Fraction

Adolescent females with diagnosis of PCOS

Hepatic Metabolism Ratios

Whole Body Insulin Sensitivity

Sleep Duration

Sleep Quality

Untreated PCOS, All participants whom the scan worked for. Did not work in those with a large waist circumference

Hepatic Phosphate Concentrations

Overall Study

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Anti-Obesity Agents

Gastrointestinal Agents

Hormones

Exenatide

Contraceptives, Oral, Combined

Glucagon

Glucagon-Like Peptide-1 Receptor Agonists

Glucagon-Like Peptide 1

Incretins

Hormone Antagonists

PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.

Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.

Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.

Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures

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

Byetta 5Mcg Pen Injection

Melanie Cree Green, MD, PhD

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.

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).

Liver and Fat Regulation in Overweight Adolescent Girls

Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls

Data will only be shared with IRB approved personnel.

Apnea Hypopnea Index (AHI) will be measured using WatchPAT. 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

Change in expression of stool microbiome species by comparing the PCOS group to samples collected from a control group without PCOS. The 5 species with the most significant will be identified and reported from a Manhattan Plot (% rate of appearance): the values above 0 represent species that are greater in the control group than in PCOS and values below 0 represent species that are greater in PCOS than in the control group.

Targeted amino acid metabolomics will be performed to measure glutamate

Targeted lipid metabolomics will be performed to measure 16n1

Targeted bile acid metabolomics will be performed to measure sphingosine-1-phospate

Hepatic glucose release will be measured by the rate of appearance of a glucose tracer.

Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy

Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer.

Hepatic de novo lipogenesis will be measured by with an acetate tracer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Post-Prandial Liver Glucose Metabolism in PCOS	NCT03041129	Polycystic Ovar... Obesity Hepatic Steatos...	oral glucose to... MRI of liver	12 Years - 21 Years	University of Colorado, Denver
Post-Prandial Liver Glucose Metabolism in PCOS	NCT03041129	Polycystic Ovar... Obesity Hepatic Steatos...	oral glucose to... MRI of liver	12 Years - 21 Years	University of Colorado, Denver
Post-Prandial Liver Glucose Metabolism in PCOS	NCT03041129	Polycystic Ovar... Obesity Hepatic Steatos...	oral glucose to... MRI of liver	12 Years - 21 Years	University of Colorado, Denver
Liver and Fat Regulation in Overweight Adolescent Girls	NCT02157974	Hepatic Steatos... Polycystic Ovar... Obesity	Byetta 5Mcg Pen...	12 Years - 21 Years	University of Colorado, Denver

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