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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.

SUBMITTER: Makimura H

PROVIDER: S-EPMC2795664 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

Makimura Hideo H Stanley Takara T Mun David D Chen Cindy C Wei Jeffrey J Connelly Jean M JM Hemphill Linda C LC Grinspoon Steven K SK

The Journal of clinical endocrinology and metabolism 20091016 12

<h4>Context</h4>Obesity is associated with reduced GH.<h4>Objective</h4>The aim of the study was to determine whether reduced GH is associated with increased carotid intima-media thickness (cIMT) in obesity.<h4>Design</h4>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 abso ...[more]

PMID: 19837914

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Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Project description:BACKGROUND:Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities. METHODS:Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values. RESULTS:Morquio A patients demonstrated significantly higher (P?<?0.001) adjusted carotid intima-media thickness (cIMT), mean (SD) of 0.56?mm (0.03) compared to control subjects, 0.44?mm (0.04). The Morquio A cohort had significantly greater adjusted carotid elasticity (carotid cross-sectional compliance +?43%, P?<?0.001; carotid incremental elastic modulus -?33%, P?=?0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%). CONCLUSIONS:Increased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.

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

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

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