Abstract
BackgroundObesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study’s purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance.Methods22 obese girls 13–21 years old were followed for a randomized 6-month trial of rhGH vs. placebo/no treatment. At baseline and 6-months, DXA was performed for body composition, MRI to measure visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT), and fasting blood drawn for IGF-1, inflammatory cardiovascular risk markers [soluble intercellular adhesion molecule (sICAM), high sensitivity CRP], lipids and HbA1C. An oral glucose tolerance test (OGTT) was performed. Twelve girls completed the 6-month visit. Baseline and mean 6-month change were compared between the groups using the Student t-test and the relationship between variables was determined through multiple regression analysis.ResultsAfter 6-months, the rhGH group maintained IGF-1 levels, and had decreases in total cholesterol (p = 0.03), sICAM-1 (p = 0.04) and HbA1C (p = 0.03) compared to placebo/no treatment. The rhGH group trended towards greater decreases in LDL and 2-hour OGTT glucose. Glucose tolerance did not worsen with rhGH administration.ConclusionsAdministering rhGH in small doses is able to stabilize IGF-1 levels in obesity. We have also shown that rhGH administration leads to an improvement in some markers of cardiovacular risk with without adversely affecting glucose tolerance.Trial registrationClinical Trial Registration Number: NCT01169103.
Highlights
Obesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk
There were no significant baseline differences noted between the blinded (N = 15) and unblinded (N = 7) groups with one exception; the waist to hip ratio (W/H) ratio was higher in the group who remained blinded to their treatment allocation (0.96 ± 0.06 vs. 0.90 ± 0.07, p = 0.05)
We have shown that administering recombinant human growth hormone (rhGH) to female adolescents in physiologic doses is able to stabilize insulin like growth factor-1 (IGF-1) in obesity, a state characterized by relative growth hormone (GH) insufficiency, without adversely affecting glucose tolerance
Summary
Obesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study’s purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance. There is a dearth of data regarding effects of GH replacement on body composition and cardiometabolic risk in otherwise healthy obese adolescents. This proof-of-concept study used rhGH as a physiologic probe to observe the effects of GH replacement on body composition. We hypothesized that rhGH administration in replacement doses to obese adolescent females would have lipolytic effects without deleterious effects on glucose tolerance
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