EFFECTS OF GH ON BODY COMPOSITION AND CARDIOVASCULAR RISK MARKERS IN MEN WITH VISCERAL ADIPOSITY: A 6-MONTH RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED TRIAL

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 695-707-Obesity Treatment
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-706
Miriam Bredella1, Eleanor Lin1, Anu Gerweck2, Melissa Landa2 and Karen Klahr Miller*3
1Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Massachusetts Gen Hosp, Boston, MA
Context: GH exerts beneficial effects on body composition and cardiovascular risk factors in men with hypopituitarism and GH deficiency. Visceral adiposity is associated with increased cardiovascular risk and decreased GH secretion.  Objective: To determine the effects of GH administration in viscerally obese men on body composition and cardiovascular risk markers. Design: 6-month, randomized, double-blind, placebo controlled study. Study participants: 62 abdominally obese men (mean BMI: 37±6 [SD] kg/m2, 18-45 years (mean age: 33±7 years). Main outcome measures: Body composition: abdominal fat depots, including visceral adipose tissue (VAT)/subcutaneous abdominal adipose tissue (SAT) ratio by CT, fat and lean mass by DXA, intramyocellular (IMCL) and intrahepatic (IHL) lipids by proton MR spectroscopy.  Cardiovascular risk markers: hsCRP, total, HDL, LDL cholesterol, apo B, fibrinogen, tPA, carotid intimal-medial thickness (IMT) and endothelial function. Results: The mean GH dose at 6 months was 1.1±0.4 (SEM) mg/day, resulting in a mean IGF-1 SDS increase from -1.9±0.5 to 0.2±1.5 and mean increase in IGF-1 of 154 ng/ml in the GH group. BMI in the whole group increased  (37.0± 6.1 kg/m2 [baseline] vs. 38.3±6.9 kg/m2 [6 months], p= 0.05) without a difference between the GH and placebo groups.  GH administration resulted in a decrease in VAT/SAT ratio (-0.06±0.08 vs. 0.01±0.08, p=0.02), a decrease in trunk-extremity fat ratio (-0.06±0.09 vs. 0.02±0.09, p=0.009), and an increase in extremity fat (0.94±1.5 vs. 0.6±1.9 kg, p=0.003) compared to placebo.  GH decreased hsCRP (-1.08±2.27 vs. 1.83±4.68 mg/L, p= 0.02), and there was a trend toward a decrease in apo B/LDL (a measure of LDL size and atherogenecity) (-0.06±0.09 vs. -0.02±0.07, p=0.1) compared with placebo. GH increased tPA (0.84±4.0 vs. -1.3±3.1 ng/ml, p=0.04) compared to placebo. After controlling for the increase in weight, there was also a significant decrease in liver fat (p=0.01), trunk fat (p=0.004), and VAT (p=0.05) in the GH group vs. placebo; the GH effect on VAT/SAT ratio increased in significance (p=0.005).  Total, LDL, HDL cholesterol, fibrinogen, IMCL, IMT and endothelial function were comparable between groups. GH increased 2-hour glucose (5.3±26.5 vs. -12.5±26.7 mg/dl, p=0.04), but not fasting glucose, vs. placebo. There was no difference in fasting glucose or 2-hour glucose levels between groups at 6 months. Five  subjects were discontinued from the study for elevated glucose parameters (4 in the GH group and 1 placebo), and 4 for carpal tunnel symptoms (3 in the GH group and 1 placebo).  Conclusion: GH replacement in viscerally obese men exerts beneficial effects on body composition and cardiovascular risk markers.  In a minority of men, it is associated with a decrease in glucose tolerance.

Nothing to Disclose: MB, EL, AG, ML, KKM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH grants R01 HL-077674, UL1 RR-025758, and K23 RR-23090.   Growth hormone and identical placebo were provided by Genentech.