NAFLD in Adolescents and Young Adults With PCOS
| Status: | Recruiting |
|---|---|
| Conditions: | Ovarian Cancer, Women's Studies, Endocrine, Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Endocrinology, Gastroenterology, Oncology, Reproductive |
| Healthy: | No |
| Age Range: | 14 - 25 |
| Updated: | 4/21/2016 |
| Start Date: | July 2013 |
| End Date: | July 2020 |
| Contact: | Hailey Roumimper, AB |
| Email: | hr2388@cumc.columbia.edu |
| Phone: | 212-305-1518 |
Nonalcoholic Fatty Liver Disease (NAFLD), Insulin Resistance and Dyslipidemia in Adolescents and Young Adults With Polycystic Ovary Syndrome (PCOS)
This project, "Nonalcoholic fatty liver disease (NAFLD), insulin resistance and dyslipidemia
in adolescents and young adults with polycystic ovary syndrome (PCOS)" focuses on an at-risk
adolescent and young adult population who may gain long-term health benefits from detection
of risk factors at a young age. The primary aims of this proposal are: 1) To observe whether
adolescents and young adults with PCOS are more likely to have elevated liver fat (>/=4.8%)
than controls by studying liver fat deposition measured by magnetic resonance spectroscopy
(MRS); 2) To assess the association of percentage liver fat with biomarkers of NAFLD,
dyslipidemia, insulin resistance and body composition in PCOS and controls.
PCOS is a common condition that frequently presents in adolescence and young adulthood and
is defined by the presence of hyperandrogenism and ovulatory dysfunction. Affected
individuals are at increased risk of insulin resistance, NAFLD and dyslipidemia, which are
features associated with the metabolic syndrome, a major public health concern. The
associations between PCOS and both insulin resistance and dyslipidemia have been extensively
described; however, its association with NAFLD has only recently been noted and
superficially studied in adolescents and young adults. Additionally, it has not yet been
fully elucidated why seemingly healthy nonobese adolescents with PCOS are predisposed to
insulin resistance and its related complications. The susceptibility of certain PCOS
patients to developing NAFLD is theorized to be due to the following potentiating factors:
insulin resistance, hyperandrogenemia, and a genetic predisposition.
In the proposed study, 40 adolescents and young adults with PCOS and 40 age-comparable
control subjects will be evaluated for metabolic disturbances and elevated liver fat using
noninvasive and state-of-the-art techniques including MRI, dual-energy x-ray absorptiometry
and an oral glucose tolerance test in order to fully assess the metabolic and body
composition differences between these groups. This research proposal represents a critical
step in understanding the metabolic and cardiovascular comorbidities of PCOS and their
relationship to NAFLD. Dr. Sopher hopes to use the results generated by this research
proposal in order to lay the groundwork for the prevention and treatment of metabolic
disorders in adolescents with PCOS. Her overarching goal is to decrease and prevent lifelong
morbidity associated with this common disorder.
in adolescents and young adults with polycystic ovary syndrome (PCOS)" focuses on an at-risk
adolescent and young adult population who may gain long-term health benefits from detection
of risk factors at a young age. The primary aims of this proposal are: 1) To observe whether
adolescents and young adults with PCOS are more likely to have elevated liver fat (>/=4.8%)
than controls by studying liver fat deposition measured by magnetic resonance spectroscopy
(MRS); 2) To assess the association of percentage liver fat with biomarkers of NAFLD,
dyslipidemia, insulin resistance and body composition in PCOS and controls.
PCOS is a common condition that frequently presents in adolescence and young adulthood and
is defined by the presence of hyperandrogenism and ovulatory dysfunction. Affected
individuals are at increased risk of insulin resistance, NAFLD and dyslipidemia, which are
features associated with the metabolic syndrome, a major public health concern. The
associations between PCOS and both insulin resistance and dyslipidemia have been extensively
described; however, its association with NAFLD has only recently been noted and
superficially studied in adolescents and young adults. Additionally, it has not yet been
fully elucidated why seemingly healthy nonobese adolescents with PCOS are predisposed to
insulin resistance and its related complications. The susceptibility of certain PCOS
patients to developing NAFLD is theorized to be due to the following potentiating factors:
insulin resistance, hyperandrogenemia, and a genetic predisposition.
In the proposed study, 40 adolescents and young adults with PCOS and 40 age-comparable
control subjects will be evaluated for metabolic disturbances and elevated liver fat using
noninvasive and state-of-the-art techniques including MRI, dual-energy x-ray absorptiometry
and an oral glucose tolerance test in order to fully assess the metabolic and body
composition differences between these groups. This research proposal represents a critical
step in understanding the metabolic and cardiovascular comorbidities of PCOS and their
relationship to NAFLD. Dr. Sopher hopes to use the results generated by this research
proposal in order to lay the groundwork for the prevention and treatment of metabolic
disorders in adolescents with PCOS. Her overarching goal is to decrease and prevent lifelong
morbidity associated with this common disorder.
Adolescents and young adult PCOS subjects and Body Mass Index (BMI), BMI z-score-, age- and
ethnicity- comparable control subjects will be screened by telephone or in person for
eligibility with the goal of recruiting 40 PCOS and 40 control subjects who are 14 to 25
years old and at least two years post-menarche. Controls and oligomenorrheic PCOS subjects
will have early morning labs, physical exam, and a two-hour oral glucose tolerance test
(OGTT) performed during the early follicular phase of their menstrual cycle (days 1-7);
amenorrheic PCOS subjects will have these studies done on any day. The protocol will
comprise:
1. History and physical exam: BMI, BMI percentile and z-score, blood pressure, assessment
of presence of acanthosis nigricans and hirsutism, smoking, alcohol and family history;
2. Laboratory evaluation will be between 0800 and 0900 after an overnight fast via a 21
gauge intravenous catheter for: 1) General endocrine panel: Thyroid function tests,
prolactin, 17-hydroxyprogesterone; 2) PCOS panel: luteinizing hormone (LH), follicle
stimulating hormone (FSH), estradiol, sex hormone binding globulin, testosterone, free
testosterone, androstenedione, dehydroepiandrosterone sulfate; 3) Liver panel: Liver
enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma
glutamyl -transpeptidase (GGT)), apoptosis markers (Fas, cytokeratin-18 fragments,
M30); 4) Cardiovascular risk panel: Cholesterol, triglycerides, high-density
lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, c-reactive protein;
5) Insulin resistance (IR) evaluation: hemoglobin A1C, glucose, insulin, c-peptide and
2 hour OGTT after a 75 g Glucola® challenge with measurement of glucose and insulin at
30, 60, 90 and 120 minutes. IR will be determined by age- and BMI- specific homeostatic
measure (HOMA) cutoffs based on a National Health and Nutrition Examination Survey
(NHANES) population study of 1,164 nonobese adolescents 12 to 19 years old. Other IR
indices that will be evaluated are whole body insulin sensitivity (WBIS) and insulin
area under the curve, which both use data from the entire two hour OGTT;
3. Magnetic resonance spectroscopy (MRS) of the liver for intrahepatic liver content
acquired using standard point resolved spectroscopy sequence (PRESS). Percentage liver
fat will be calculated;
4. Total body magnetic resonance imaging (MRI) with 10 mm slices and 40 mm interslice gaps
for total body adipose tissue and visceral adipose tissue (VAT);
5. Dual-energy x-ray absorptiometry (DXA): Total body DXA for total body lean and fat mass
and body fat percentage. Percentage liver fat greater than or equal to 4.8% will be
considered elevated in this young and healthy population. MRI studies will be attained
by a General Electric 1.5 T LX PRI system; DXA studies will be performed with the
Hologic Discovery W using appropriate age-, sex- and ethnicity-specific references.
ethnicity- comparable control subjects will be screened by telephone or in person for
eligibility with the goal of recruiting 40 PCOS and 40 control subjects who are 14 to 25
years old and at least two years post-menarche. Controls and oligomenorrheic PCOS subjects
will have early morning labs, physical exam, and a two-hour oral glucose tolerance test
(OGTT) performed during the early follicular phase of their menstrual cycle (days 1-7);
amenorrheic PCOS subjects will have these studies done on any day. The protocol will
comprise:
1. History and physical exam: BMI, BMI percentile and z-score, blood pressure, assessment
of presence of acanthosis nigricans and hirsutism, smoking, alcohol and family history;
2. Laboratory evaluation will be between 0800 and 0900 after an overnight fast via a 21
gauge intravenous catheter for: 1) General endocrine panel: Thyroid function tests,
prolactin, 17-hydroxyprogesterone; 2) PCOS panel: luteinizing hormone (LH), follicle
stimulating hormone (FSH), estradiol, sex hormone binding globulin, testosterone, free
testosterone, androstenedione, dehydroepiandrosterone sulfate; 3) Liver panel: Liver
enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma
glutamyl -transpeptidase (GGT)), apoptosis markers (Fas, cytokeratin-18 fragments,
M30); 4) Cardiovascular risk panel: Cholesterol, triglycerides, high-density
lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, c-reactive protein;
5) Insulin resistance (IR) evaluation: hemoglobin A1C, glucose, insulin, c-peptide and
2 hour OGTT after a 75 g Glucola® challenge with measurement of glucose and insulin at
30, 60, 90 and 120 minutes. IR will be determined by age- and BMI- specific homeostatic
measure (HOMA) cutoffs based on a National Health and Nutrition Examination Survey
(NHANES) population study of 1,164 nonobese adolescents 12 to 19 years old. Other IR
indices that will be evaluated are whole body insulin sensitivity (WBIS) and insulin
area under the curve, which both use data from the entire two hour OGTT;
3. Magnetic resonance spectroscopy (MRS) of the liver for intrahepatic liver content
acquired using standard point resolved spectroscopy sequence (PRESS). Percentage liver
fat will be calculated;
4. Total body magnetic resonance imaging (MRI) with 10 mm slices and 40 mm interslice gaps
for total body adipose tissue and visceral adipose tissue (VAT);
5. Dual-energy x-ray absorptiometry (DXA): Total body DXA for total body lean and fat mass
and body fat percentage. Percentage liver fat greater than or equal to 4.8% will be
considered elevated in this young and healthy population. MRI studies will be attained
by a General Electric 1.5 T LX PRI system; DXA studies will be performed with the
Hologic Discovery W using appropriate age-, sex- and ethnicity-specific references.
Inclusion Criteria:
- All: Healthy; between 14 and 25 years; at least 2 years postmenarche
- PCOS: Clinical hyperandrogenism and/or hyperandrogenemia, menstrual dysfunction
(oligomenorrhea or amenorrhea) and exclusion of other known disorders. PCOS will be
diagnosed using the NIH 1990 criteria.
- Controls: Regular menses; no clinical hyperandrogenism and/or hyperandrogenemia
Exclusion Criteria:
- Past or present history of a medical disorder or medication known to affect body
composition, insulin secretion and sensitivity, or the growth hormone
(GH)-insulin-like growth factor 1 (IGF1) axis (eg steroid hormone or thyroid
replacement).
- History of current or past pregnancy
- Hormonal contraceptive or metformin use within 3 months of enrollment
- Nonclassical congenital adrenal hyperplasia
We found this trial at
1
site
630 W 168th St
New York, New York
New York, New York
212-305-2862
Principal Investigator: Aviva B Sopher, MD, MS, MS
Phone: 212-305-1518
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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