Epidemiologic studies have clearly demonstrated that patients with a preponderance of abdominal or visceral adiposity are at profoundly higher risk for cardiovascular disease than those with preferential accumulation of body fat in the gluteofemoral region. Atherogenic abnormalities associated with visceral adiposity include increases in inflammatory cardiovascular risk markers, dyslipidemia and insulin resistance. Cardiovascular disease is the leading cause of death and illness in developed countries. Therefore, the investigation of possible mechanisms underlying the increased cardiovascular risk in patients with visceral adiposity is critical, as is the development of potential therapies for this disorder. An elevated risk of visceral adiposity and cardiovascular risk has been established in men and women with growth hormone (GH) deficiency due to hypopituitarism. Studies have been fundamental in establishing that decreased GH secretion is an independent risk factor for visceral obesity and cardiovascular disease in such patients. GH administration has been shown to decrease visceral adiposity in women with GH deficiency due to hypopituitarism, but cardiovascular risk markers have not been studied, nor have men and women with GH deficiency due to obesity in the absence of pituitary disease. Our preliminary data suggest a strong association between GH deficiency, truncal adiposity and increased cardiovascular risk markers in overweight normal women without pituitary disease. This is consistent with limited published studies suggesting that GH secretion may be reduced in morbidly obese compared with lean men and women in the absence of pituitary disease. In this proposal, we will investigate, in a double-blind, randomized, placebo-controlled protocol whether low-dose GH administration improves markers of cardiovascular risk in parallel with reductions in visceral fat mass in the normal men and women with visceral adiposity and diminished GH secretion. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL077674-01A2
Application #
7265459
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Aviles-Santa, Larissa
Project Start
2007-08-15
Project End
2012-07-31
Budget Start
2007-08-15
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$585,868
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph et al. (2017) The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease. Clin Transl Gastroenterol 8:e217
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Dichtel, Laura E; Schorr, Melanie; Gill, Corey M et al. (2017) Body composition in pituitary, adrenal and iatrogenic Cushing's syndrome and effects of DHEAS levels. Clin Endocrinol (Oxf) 86:160-162
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Bachmann, Katherine N; Bruno, Alexander G; Bredella, Miriam A et al. (2016) Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women. J Bone Miner Res 31:281-8
Karastergiou, Kalypso; Bredella, Miriam A; Lee, Mi-Jeong et al. (2016) Growth hormone receptor expression in human gluteal versus abdominal subcutaneous adipose tissue: Association with body shape. Obesity (Silver Spring) 24:1090-1096
Bove, Riley M; Gerweck, Anu V; Mancuso, Sarah M et al. (2016) Association between adiposity and cognitive function in young men: Hormonal mechanisms. Obesity (Silver Spring) 24:954-61

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