Prevalence and Cardiovascular Effects of Growth Hormone Deficiency in Abdominal Obesity

Prevalence and Metabolic Consequences of Relative Growth Hormone Deficiency in Abdominal Obesity

Obesity is one of the leading causes of cardiovascular-related diseases, including diabetes and heart disease. Obesity, and more specifically abdominal obesity, may cause decreased growth hormone (GH) levels. It is believed that GH deficiency may contribute to increased cardiovascular risk by affecting insulin resistance, inflammatory markers, and blood cholesterol levels. This study will determine the occurrence of GH deficiency in abdominal obesity and whether GH deficiency is associated with increased cardiovascular risk beyond traditional risk factors.

Obesity is associated with significant morbidity and mortality and is a primary public health concern. Both the incidence and prevalence of obesity have increased over the last several decades, with obesity now affecting an estimated 31% of the American population. Recent data suggest that people with abdominal obesity commonly exhibit low levels of GH, which affects the body's growth rate and the way the body uses food for energy. Low GH levels and excess abdominal fat have been linked to improper functioning of the cardiovascular system and, therefore, may increase one's risk of cardiovascular disease. This study will determine the prevalence of GH deficiency in abdominal obesity and whether GH deficiency is associated with increased cardiovascular risk beyond traditional risk factors.

Participation in this observational study will last between 2 and 4 weeks. The study will consist of two outpatient visits, held at either the Massachusetts General Hospital or Massachusetts Institute of Technology. Visit 1 will last 4 hours and will include a physical exam, medical history, blood draw, urine sampling, indirect calorimetry test, and growth hormone releasing hormone (GHRH)+Arginine stimulation test. Eligible participants will return within the next 3 weeks for Visit 2, which will last 5 hours. Before the second visit, participants will be asked to record their food intake for 4 days on a food record. During the visit, participants will have a repeat physical exam, urine sampling, and blood draw. Participants will also undergo an oral glucose tolerance test, whole body DEXA scan, abdominal computed tomography (CT) scan, and a carotid ultrasound. Participation in the study will end after Visit 2.

Inclusion Criteria for Obesity:

• Body mass index (BMI) greater than or equal to 30 kg/m2
• Abdominal obesity, defined as waist circumference greater than or equal to 102 cm in men and greater than or equal to 88 cm in women

Inclusion Criteria for Lean Controls:

• BMI less than 25 kg/m2
• Waist circumference less than 102 cm in men and less than 88 cm in women

Exclusion Criteria for both groups:

• Obesity due to known secondary causes
• Taking any weight lowering drugs
• Previous bariatric surgery
• Use of the following compounds within the 3 months prior to study entry: estrogen, progesterone, GH, GHRH, glucocorticoids, megesterol acetate, antidiabetic agents, oral contraceptive pills, or any other hormone or drug known to affect GH levels
• Change in lipid lowering or antihypertensive regimen within 3 months prior to study entry
• Use of testosterone or hormone replacement therapy
• Previously known diabetes mellitus or other severe chronic illness
• Hemoglobin less than 11.0 g/dL, creatinine greater than 1.5 mg/dL, or serum glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times the upper limit of normal
• Follicle stimulating hormone (FSH) greater than 20 IU/L in women
• Positive urine pregnancy test
• Prior history of pituitary disease, pituitary surgery, head irradiation, or any other condition known to affect the GH axis