Reduced growth hormone secretion is associated with increased carotid intima-media thickness in obesity

Abstract

Context: Obesity is associated with reduced GH.

Objective: The aim of the study was to determine whether reduced GH is associated with increased carotid intima-media thickness (cIMT) in obesity.

Design: 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00562796.

Figures

Figure 1

Peak GH and cIMT. A, Peak stimulated GH is negatively associated with cIMT on univariate analysis. Men are depicted with open diamonds, whereas women are depicted with closed squares. B, Relative GHD was determined by peak stimulated GH of 4.2 μg/liter or less on standard GHRH-arginine stimulation test. cIMT is significantly different across groups by overall ANOVA (P = 0.01). Between-group comparisons with Tukey-Kramer post hoc tests show that cIMT is similar between normal-weight and obese GHS subjects (P = NS) but significantly different between normal-weight and obese subjects with relative GHD (P < 0.05).

Figure 2

The association of peak stimulated GH on standard GHRH-arginine stimulation test and inflammatory markers by univariate analysis. Men are depicted with open diamonds, whereas women are depicted with closed squares. A, Peak stimulated GH is negatively associated with serum CRP. B, Peak stimulated GH is positively associated with serum adiponectin. C, Peak stimulated GH is negatively associated with serum TNF-α.