CiteULike: omalbams Grobbee

Variations in the uncoupling protein-3 gene are associated with specific obesity phenotypes

Annet van Abeelen — 2008-04-21T19:09:45-00:00

Eur J Endocrinol, Vol. 158, No. 5. (1 May 2008), pp. 669-676.

ObjectiveUncoupling protein 3 (UCP-3) uncouples oxidative metabolism from ATP synthesis, resulting in the production of heat instead of energy storage. Single nucleotide polymorphisms (SNPs) in UCP-3 might result in a reduced function or expression of UCP-3 and therefore lead to an increased capacity to store energy as fat. DesignWe conducted a population-based, cross-sectional single-center study among 400 Dutch men between 40 and 80 years. MethodsSeven SNPs in the UCP-3 gene were genotyped by means of an allele-specific real-time TaqMan PCR. Linear regression analyses were performed to examine the independent effects of these SNPs on obesity phenotypes. ResultsWe found a significant association between homozygosity for the minor allele of rs647126, rs1685356, and rs2075577 and an increase in body mass index (BMI; P=0.033, P=0.016, and P=0.019 respectively). Heterozygosity for rs1685354 was associated with a significant decrease in visceral fat mass (P=0.030). ConclusionsOur results suggest that genetic variations in the UCP-3 gene are associated with an increase in BMI. A plausible mechanism by which these SNPs lead to an increase in BMI is that due to these SNPs, the UCP-3 activity might be decreased. As a result, uncoupling activity may also decrease, which will lead to an increase in body weight and BMI. 10.1530/EJE-07-0834

Oral testosterone supplementation and chronic low-grade inflammation in elderly men: a 26-week randomized, placebo-controlled trial.

HR Nakhai-Pour — 2008-01-27T19:56:29-00:00

Am Heart J, Vol. 154, No. 6. (December 2007)

BACKGROUND: To determine the effect of oral testosterone supplementation on systemic low-grade inflammation measured by high-sensitive C-reactive protein (hs-CRP) in aging men with low testosterone levels. METHODS: Two hundred thirty-seven men aged 60 to 80 years with a testosterone level of <13.7 nmol/L (below the 50th percentile of the population distribution) were recruited into a double-blind randomized placebo-controlled trial. Participants were randomized to either 4 capsules of 40 mg testosterone undecanoate (Andriol Testocaps, NV Organon, Oss, The Netherlands) or placebo daily for 26 weeks. Serum levels of hs-CRP were measured at baseline and at 26 weeks using a near-infrared particle immunoassay of the Synchron LX System (Beckman Coulter, Fullteron, CA). RESULTS: The median baseline hs-CRP level was 1.95 mg/L (0.30-6.43) in the testosterone group compared with 1.90 mg/L (0.40-5.91) in the placebo group. After 26 weeks of testosterone supplementation therapy, the 2 intervention groups were not statistically significantly different (median hs-CRP 2.20 vs 2.00 mg/L, interquartile range 0.40-6.54 vs 0.50-5.70, P = .36). In subgroup analysis, neither baseline testosterone level, nor age, nor baseline CRP-level modified the effect of testosterone supplementation on CRP levels. CONCLUSION: Oral testosterone undecanoate supplementation, in dosage of 160 mg daily for 26 weeks, does not increase hs-CRP levels in elderly men.

Endogenous Sex Hormones and Metabolic Syndrome in Aging Men

Majon Muller — 2008-01-11T03:21:57-00:00

J Clin Endocrinol Metab, Vol. 90, No. 5. (1 May 2005), pp. 2618-2623.

Background: Sex hormone levels in men change during aging. These changes may be associated with insulin sensitivity and the metabolic syndrome. Methods: We studied the association between endogenous sex hormones and characteristics of the metabolic syndrome in 400 independently living men between 40 and 80 yr of age in a cross-sectional study. Serum concentrations of lipids, glucose, insulin, total testosterone (TT), SHBG, estradiol (E2), and dehydroepiandrosterone sulfate (DHEA-S) were measured. Bioavailable testosterone (BT) was calculated using TT and SHBG. Body height, weight, waist-hip circumference, blood pressure, and physical activity were assessed. Smoking and alcohol consumption was estimated from self-report. The metabolic syndrome was defined according to the National Cholesterol Education Program definition, and insulin sensitivity was calculated by use of the quantitative insulin sensitivity check index. Results: Multiple logistic regression analyses showed an inverse relationship according to 1 SD increase for circulating TT [odds ratio (OR) = 0.43; 95% confidence interval (CI), 0.32-0.59], BT (OR = 0.62; 95% CI, 0.46-0.83), SHBG (OR = 0.46; 95% CI, 0.33-0.64), and DHEA-S (OR = 0.76; 95% CI, 0.56-1.02) with the metabolic syndrome. Each SD increase in E2 levels was not significantly associated with the metabolic syndrome (OR = 1.16; 95% CI, 0.92-1.45). Linear regression analyses showed that higher TT, BT, and SHBG levels were related to higher insulin sensitivity; beta-coefficients (95% CI) were 0.011 (0.008-0.015), 0.005 (0.001-0.009), and 0.013 (0.010-0.017), respectively, whereas no effects were found for DHEA-S and E2. Estimates were adjusted for age, smoking, alcohol consumption, and physical activity score. Further adjustment for insulin levels and body composition measurements attenuated the estimates, and the associations were similar in the group free of cardiovascular disease and diabetes. Conclusions: Higher testosterone and SHBG levels in aging males are independently associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, independent of insulin levels and body composition measurements, suggesting that these hormones may protect against the development of metabolic syndrome. 10.1210/jc.2004-1158

Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial.

MH Emmelot-Vonk — 2008-01-07T22:38:03-00:00

JAMA, Vol. 299, No. 1. (2 January 2008), pp. 39-52.

CONTEXT: Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might beneficially affect the aging processes. OBJECTIVE: To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone mineral density, body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherlands. INTERVENTION: Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months. MAIN OUTCOME MEASURES: Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test, isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments), bone mineral density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose, and insulin), quality of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters (serum prostate-specific antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hemoglobin, and hematocrit). RESULTS: A total of 207 men completed the study. During the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the placebo group had the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related quality-of-life measure that improved. No negative effects on prostate safety were detected. CONCLUSION: Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN23688581.

High dietary glycemic load and glycemic index increase risk of cardiovascular disease among middle-aged women: a population-based follow-up study.

JW Beulens — 2007-09-04T06:30:50-00:00

J Am Coll Cardiol, Vol. 50, No. 1. (3 July 2007), pp. 14-21.

OBJECTIVES: The goal of this work was to assess whether high dietary glycemic load and glycemic index are associated with an increased risk of cardiovascular disease (CVD). BACKGROUND: The associations of dietary glycemic index and glycemic load with risk of CVD are not well established, particularly in populations consuming modest glycemic load diets. Moreover, risk may differ between lean and overweight subjects. METHODS: Associations of glycemic index and glycemic load with incident CVD were examined in a prospective cohort of 15,714 Dutch women age 49 to 70 years without diabetes or CVD. Dietary glycemic index and glycemic load were calculated using the glycemic index, carbohydrate content, and frequency of intake of individual foods. RESULTS: During 9 +/- 2 years of follow-up, 556 cases of coronary heart disease (CHD) and 243 cases of cerebrovascular accident (CVA) occurred. Dietary glycemic load (mean = 100; SD = 17) was associated with increased risk of CVD, adjusted for CVD risk factors and dietary variables, with a hazard ratio (HR) for the highest against lowest quartile of 1.47 (95% confidence interval [CI] 1.04 to 2.09; p(trend) = 0.03). Similar results were observed for dietary glycemic index with a corresponding HR of 1.33 (95% CI 1.07 to 1.67; p(trend) = 0.02). Glycemic load tended to be associated with both CHD (HR 1.44; 95% CI 0.95 to 2.19; p(trend) = 0.14) and CVA (HR 1.55; 95% CI 0.81 to 2.97; p(trend) = 0.10), but glycemic index only with CHD (HR 1.44; 95% CI 1.10 to 1.89; p(trend) = 0.01). Among overweight women (body mass index >25 kg/m2), glycemic load was associated with CVD (1.78; 95% CI 1.11 to 2.85; p(trend) = 0.04), but not among normal weight women (p(interaction) = 0.19). Body mass index did not modify the association of glycemic index with CVD. CONCLUSIONS: Among women consuming modest glycemic load diets, high dietary glycemic load and glycemic index increase the risk of CVD, particularly for overweight women.