Growth Hormone, Cardiovascular Risk, and Visceral Adiposity

Not Applicable

Completed

Interventions: Drug: Placebo Growth Hormone
Drug: Nutropin AQ growth hormone

Brief Summary: This study will compare growth hormone levels and cardiovascular risk markers in normal weight and overweight women and men. In women and men with increased abdominal weight, growth hormone (GH) versus placebo will be administered and effects on cardiovascular risk, insulin resistance and body composition will be measured.

Detailed Description: The purpose of this study is to measure growth hormone levels in women and men who are normal weight, overweight, and obese. Growth hormone levels will be correlated with body weight, body composition, and markers of cardiovascular risk. In overweight or obese women and men with increased visceral adiposity and below average IGF-1 levels, growth hormone versus placebo will be given for 6 months. Effects of growth hormone treatment on weight, body composition, insulin resistance, lipids, and cardiovascular risk markers will then be assessed. Study subjects will be followed for an additional six months for these endpoints.

Recruitment & Eligibility

Inclusion Criteria

For growth hormone measurement part (for men and women):
1. For visceral adiposity arm: waist circumference greater than or equal to 88 cm for women or 102 cm for men, and BMI greater than or equal to 25 kg/m2
2. For lean controls: BMI 18.5 to 24.9 kg/m2
For growth hormone treatment part (for men and women):
1. Visceral adiposity (waist circumference greater than or equal to 88 cm for women and 102 for men, BMI greater than or equal to 25 kg/m2)
2. IGF-I within the lowest 2 quartiles for age and gender
3. Willingness to maintain current activity level and diet

Exclusion Criteria

Diabetes mellitus (fasting plasma glucose greater than 126 mg/dL or 2-hour post-oral glucose tolerance test [OGTT] plasma glucose greater than 200)
Taking the following medications in the last 3 months: weight loss or lipid-lowering agents, medications to treat diabetes mellitus or "pre-diabetes", oral contraceptives or estrogen-containing medications, other medications known to significantly affect weight
Smoking
Hematocrit below the lower limit of normal
Amenorrhea for 3 months (in women)
Pregnant or breastfeeding (in women)
Polycystic ovary syndrome (in women)
Weight that exceeds 280 pounds
SGPT greater than 2 times the upper limit of normal
History of malignancy, except for fully resolved basal cell carcinomas of the skin (Specific Aim 2 only)
Radiation exposure greater than 1000 mrem over the last 12 months
Previous diagnosis of cardiovascular disease
History of pituitary or hypothalamic disease, brain radiation, or childhood growth hormone deficiency
History of carpal tunnel syndrome that has not been surgically treated

Arm && Interventions

Group	Intervention	Description
Male on Placebo	Placebo Growth Hormone	Participants received placebo. Placebo Growth Hormone : Participants gave themselves injections of placebo every night for 6 months.
Female on GH	Nutropin AQ growth hormone	Participants received growth hormone replacement therapy. The starting dose was 4 micrograms/kg per day and they were titrated within the normal range based on blood levels. Nutropin AQ growth hormone : Participants gave themselves injections of growth hormone every night for 6 months.
Female on Placebo	Placebo Growth Hormone	Participants received placebo. Placebo Growth Hormone : Participants gave themselves injections of placebo every night for 6 months.
Male on GH	Nutropin AQ growth hormone	Participants received growth hormone replacement therapy. The starting dose was 2 micrograms/kg per day and they were titrated within the normal range based on blood levels. Nutropin AQ growth hormone : Participants gave themselves injections of growth hormone every night for 6 months.

Primary Outcome Measures

Name	Time	Method
HsCRP	Measured at baseline and month 6	6 month change in HsCRP (primary cardiovascular risk endpoint)
Total Abdominal Fat	Measured at baseline and month 6	6 month change in total abdominal fat (primary body composition endpoint)
Abdominal Fat	Measured at baseline and month 6	6 month change in visceral abdominal fat (primary body composition endpoint)

Secondary Outcome Measures

Name	Time	Method
Measure of Insulin Resistance	Measured at baseline and month 6	6 month change in 2-hour glucose (primary insulin resistance endpoint)
Insulin-like Growth Factor-1 (IGF-1) Levels	Measured at baseline and month 6	6-month change in IGF-1 levels