Reduced Growth Hormone Secretion Is Associated with Increased Carotid Intima-Media Thickness in Obesity

Abstract

Obesity is associated with reduced GH. The aim of the study was to determine whether reduced GH is associated with increased carotid intima-media thickness (cIMT) in obesity. A total of 102 normal-weight and obese men and women without known hypopituitarism were studied. Subjects underwent GH stimulation testing with GHRH-arginine. Lipid profile, inflammatory markers, oral glucose tolerance test, abdominal computed tomography, dual-energy x-ray absorptiometry, and cIMT were measured. Relative GH deficiency was defined as peak GH of 4.2 microg/liter or less. Subjects were separated based on BMI and GH testing into three groups: normal weight, obese GH sufficient (GHS), and obese relative GH deficient (GHD). Age, gender, and race were similar between the groups. BMI, percentage body fat, and visceral adiposity did not differ between obese GHS and relative GHD. Peak GH was associated with cIMT, IGF-I, high-density lipoprotein, low-density lipoprotein, triglycerides, adiponectin, C-reactive protein, and TNF-alpha (all P < 0.05). Obese GHS subjects had similar cIMT compared to normal-weight subjects (P = not significant), whereas obese GHD subjects had higher cIMT compared to normal-weight subjects (P < 0.05) (normal weight, 0.645 +/- 0.023, vs. obese GHS, 0.719 +/- 0.021, vs. obese GHD, 0.795 +/- 0.063 mm; P = 0.01 by ANOVA). Similar results were seen in sensitivity analyses with less stringent cutoffs (< 5, < or = 8, < 9 microg/liter) to define GHD. In multivariate modeling, peak GH remained significantly associated with cIMT after controlling for age, gender, race, tobacco, blood pressure, cholesterol, and fasting glucose (R(2) for model, 0.35; P < 0.0001). These results suggest that reduced GH secretion is associated with a more abnormal metabolic phenotype in obesity, characterized by increased cIMT, dyslipidemia, insulin resistance, and inflammation.