Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Heart and Blood Diseases

Syndrome

Obesity

Polycystic Ovary Syndrome

Prehypertension

Prediabetic State

Metabolic Syndrome

Glucose Intolerance

Insulin Resistance

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

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

Vascular Diseases

Subjects assigned to heat therapy underwent 30 1-hour hot tub sessions over 8-10 weeks (3-4 per week). The hot tub was set to 40.5 Celsius, and core temperature and heart rate were monitored throughout each session.Subjects were instructed to not make any other dietary or lifestyle changes.Cardiovascular and metabolic health assessments were made Pre (0 heat sessions), mid (after 14-16 heat sessions, \~4-5 weeks), and post (after all 30 heat sessions; \~8-10 weeks).

Subjects were monitored at matched timepoints (start of study, 4-5 weeks, and 8-10 weeks) but not exposed to any intervention. Subjects were instructed to not make any dietary or lifestyle changes.

Heat therapy

Traditional medical treatments are often based on research done exclusively in males, and recent research efforts in the physiology community have highlighted critical sex differences in disease presentation and progression. For example, the relative risk of fatal heart disease is 50% greater in obese, diabetic women as compared to their male counterparts, and women appear to respond differently to lifestyle interventions such as exercise compared with men. Chronic passive heat exposure (hot tub use) provides alternative or supplemental therapeutic potential for improving cardiovascular and metabolic health in obese women. In addition, passive heat exposure may offer specific cellular protection from stresses like a lack of blood flow (ischemia), which is the primary cause of fatal coronary heart disease. This study is investigating the possible cardiovascular and metabolic health benefits of chronic passive heat exposure, and whether regular hot tub use (3-4 days per week for 8-10 weeks) may reduce obese womens' cardiometabolic risk. The investigators are examining cardiovascular health through blood pressure, blood vessel stiffness, sympathetic ('fight or flight') activity, and responsiveness to stresses like increased or decreased blood flow. The investigators are also examining metabolic health through an oral glucose tolerance test and a subcutaneous fat biopsy. The goal of this research is to develop a therapy targeted toward the specific health needs and complications of obese women, in an effort to improve cardiovascular and metabolic health and provide therapeutic alternatives in this high-risk population.

Subjects were matched for age and BMI, then assigned to either a heat therapy intervention or time control (no intervention, just outcomes assessment at matched timepoints).

It was not possible to blind the subject or PI to treatment group, but all measures that were collected were analyzed offline by a blinded investigator.

Heat Therapy and Cardiometabolic Health in Obese Women

serum measurement of high-sensitivity C-reactive protein, global inflammatory marker

Resting supine blood pressure, measured in triplicate with median recorded

glucose and insulin responses to a 75-g, 2-hr oral glucose tolerance test after a 12+hr fast

recording of sympathetic nerve traffic during supine rest, quantified as burst count per minute

intimal thickness of common carotid artery assessed using doppler ultrasonography

intimal thickness of superficial femoral artery assessed using doppler ultrasonography

arterial compliance of common carotid artery measured using ultrasonography

arterial compliance of superficial femoral artery measured using ultrasonography

flow-mediated dilation of brachial artery, expressed as % change in diameter. A measure of endothelial function.

flow-mediated dilation of brachial artery, expressed as % change in diameter, following 20 minute ischemia-20 minute reperfusion. A measure of vascular tolerance to ischemia-reperfusion stress.

Adipose tissue sample analyzed for insulin signaling, markers of inflammation, and heat shock protein expression

American Heart Association

University of Oregon

Kenneth & Kenda Singer Endowed Professor

Digestive System Diseases

Rare Diseases

Fatty Liver

Liver Diseases

Gastrointestinal 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

Musculoskeletal Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Diabetes Mellitus

Fibrous Dysplasia of Bone

Neoplasms, Cystic, Mucinous, and Serous

Fibrous Dysplasia, Polyostotic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Osteochondrodysplasias

Mucopolysaccharidosis IV

Bone Diseases

Bone Diseases, Developmental

Fibrous Dysplasia

McCune-Albright Syndrome

Mucopolysaccharidosis Type IV

Insulin

Insulin, Globin Zinc

Fibrous Dysplasia/McCune-Albright Syndrome with diabetes mellitus.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and without intraductal papillary mucinous neoplasms.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Fibrous Dysplasia/McCune-Albright Syndrome without diabetes mellitus and with intraductal papillary mucinous neoplasms.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Participants will receive the following interventions: Hyperinsulinemic Euglycemic Clamp and 2H20; Hyperglycemic Clamp; and Oral Glucose Tolerance Test.

Test is used to assess insulin effects on hepatic glucose production.

Hyperinsulinemic Euglycemic Clamp and 2H20

Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.

Hyperglycemic Clamp

The oral glucose tolerance test (OGTT) measures the body's ability to use a type of sugar, called glucose, that is the body's main source of energy. An OGTT can be used to diagnose prediabetes and diabetes.

Oral Glucose Tolerance Test

Cemre Robinson, MD

The investigators' objective is to understand the pathogenesis of diabetes mellitus in Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) by: 1) establishing the contributions of insulin resistance versus impaired insulin secretion, 2) investigating presence of excess glucagon signaling by measuring gluconeogenesis and glycogenolysis, and 3) investigating a potential interaction between diabetes and intraductal papillary mucinous neoplasms (IPMNs).

Specific project aims include:

Aim 1: Determine insulin secretion and sensitivity in subjects with MAS-associated diabetes.

Aim 2: Measure gluconeogenesis and glycogenolysis in MAS-associated diabetes to investigate a potential role for excess glucagon signaling.

Aim 3: Determine if IPMN development is associated with impairment of insulin secretion prior to development of overt diabetes.

The authors expect that this study will:

1. Establish the etiology of diabetes in FD/MAS
2. Increase understanding of the role of IPMNs in pathogenesis of diabetes
3. Provide critical insights into the pathogenesis of diabetes in FD/MAS

Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome

The test detects deletions in the HNF4A, GCK, HNF1A, HNF1B genes and mutations in the HNF4A, GCK, HNF1A, HNF1B and IPF1. Will be obtained at baseline before the start of oral glucose tolerance test only in those subjects with an existing diagnosis of diabetes mellitus.

An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects have pre-IGT, IGT or diabetes

This primary outcome will be obtained from the oral glucose tolerance test

This primary outcome will be obtained from the hyperglycemic clamp

AIRmax stimulation test during the hyperglycemic clamp to ascertain the maximal acute insulin response (AIR) to arginine, which is a measure of functional beta cell capacity.

Measurements from the Hyperinsulinemic Euglycemic Clamp/ 2H20 Study will be used to assess insulin effects on hepatic glucose production and glycerol kinetics isotopes and the deuterium enrichment at carbons 2 and 5 (C2 and C5) of plasma glucose providing information on glucose fluxes

Peripheral blood draw before the start of oral glucose tolerance test

Peripheral blood draw at the end of the oral glucose tolerance test

Will be obtained at baseline before the start of oral glucose tolerance test to look for albuminuria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Heat Therapy and Cardiometabolic Health in Obese Women	NCT03644524	Obesity Polycystic Ovar... Prehypertension PreDiabetes Cardiovascular ... Metabolic Syndr...	Heat therapy	18 Years - 40 Years	University of Oregon
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
Heat Therapy and Cardiometabolic Health in Obese Women	NCT03644524	Obesity Polycystic Ovar... Prehypertension PreDiabetes Cardiovascular ... Metabolic Syndr...	Heat therapy	18 Years - 40 Years	University of Oregon
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
Characterization of Diabetes Mellitus in Fibrous Dysplasia/McCune-Albright Syndrome	NCT03520153	McCune-Albright... Fibrous Dysplas... Intraductal Pap... Diabetes Mellit...	Hyperinsulinemi... Hyperglycemic C... Oral Glucose To...	18 Years -	Yale University
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

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