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Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids.

ABSTRACT: To determine the effects of dehydroepiandrosterone (DHEA) therapy on changes in central adiposity, insulin action and blood lipids. Many of the actions of DHEA in humans are thought to be mediated through its conversion to sex hormones, which are modulators of adiposity, muscularity and insulin sensitivity. The effects of DHEA replacement on regional tissue composition, glucose metabolism and blood lipid profile in older adults have been inconsistent.A randomized, double-blinded, placebo-controlled trial. The intervention was oral DHEA 50 mg/day or placebo for 12 months.Fifty-eighty women and 61 men, aged 60-88 years, with low serum DHEA sulphate (DHEAS) levels at study entry.Computed tomography measures of abdominal fat areas, thigh muscle and fat areas, DXA-derived trunk fat mass, serum glucose and insulin responses to an oral glucose challenge, and fasted serum total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were assessed before and after the intervention.There were no significant (P > 0·05) differences between the DHEA and placebo groups in the changes in regional tissue composition or glucose metabolism. HDL-cholesterol (P = 0·01) and fasted triglycerides (P = 0·02) decreased in women and men taking DHEA.Restoring serum DHEAS levels in older adults to young adult levels for 1 year does not appear to reduce central adiposity or improve insulin action. The benefit of DHEA on decreasing serum triglycerides must be weighed against the HDL-lowering effect.

SUBMITTER: Jankowski CM

PROVIDER: S-EPMC3166648 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids.

Jankowski Catherine M CM Gozansky Wendolyn S WS Van Pelt Rachael E RE Wolfe Pamela P Schwartz Robert S RS Kohrt Wendy M WM

Clinical endocrinology 20111001 4

<h4>Objective</h4>To determine the effects of dehydroepiandrosterone (DHEA) therapy on changes in central adiposity, insulin action and blood lipids. Many of the actions of DHEA in humans are thought to be mediated through its conversion to sex hormones, which are modulators of adiposity, muscularity and insulin sensitivity. The effects of DHEA replacement on regional tissue composition, glucose metabolism and blood lipid profile in older adults have been inconsistent.<h4>Design</h4>A randomized ...[more]

PMID: 21521341

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Project description:BACKGROUND AND AIM:Cardiovascular diseases (CVDs) are globally the leading cause of death and hypertension is a significant risk factor. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with decreases in blood pressure and CVD risk. Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD. METHODS:This cross-sectional study included 837 Danish individuals from the ADDITION-PRO cohort (52% men, median (interquartile range) age 65.5 (59.8 to 70.7) years, BMI 26.1 (23.4 to 28.5) kg/m2, without antihypertensive treatment and known diabetes). All participants received an oral glucose tolerance test with measurements of GLP-1 at 0, 30 and 120 min. Aortic stiffness was assessed by pulse wave velocity (PWV). The associations between GLP-1 response and central and brachial blood pressure (BP) and PWV were assessed in linear regression models adjusting for age and sex. RESULTS:A greater GLP-1 response was associated with lower central systolic and diastolic BP of -?1.17 mmHg (95% confidence interval (CI) -?2.07 to -?0.27 mmHg, P?=?0.011) and -?0.74 mmHg (95% CI -?1.29 to -?0.18 mmHg, P?=?0.009), respectively, as well as lower brachial systolic and diastolic BP of -?1.27 mmHg (95% CI -?2.20 to -?0.33 mmHg, P?=?0.008) and -?1.00 (95% CI -?1.56 to -?0.44 mmHg, P?=?0.001), respectively. PWV was not associated with GLP-1 release (P?=?0.3). Individuals with the greatest quartile of GLP-1 response had clinically relevant lower BP measures compared to individuals with the lowest quartile of GLP-1 response (central systolic BP: -?4.94 (95% CI -?8.56 to -?1.31) mmHg, central diastolic BP: -?3.05 (95% CI -?5.29 to -?0.80) mmHg, brachial systolic BP: -?5.18 (95% CI -?8.94 to -?1.42) mmHg, and brachial diastolic BP: -?2.96 (95% CI -?5.26 to -?0.67) mmHg). CONCLUSION:Greater glucose-stimulated GLP-1 responses were associated with clinically relevant lower central and peripheral blood pressures, consistent with beneficial effects on the cardiovascular system and reduced risk of CVD and mortality. Trial registration ClinicalTrials.gov Identifier: NCT00237549. Retrospectively registered 10 October 2005.

Project description:Importance:The sequelae of gestational diabetes (GD) by contemporary criteria that diagnose approximately twice as many women as previously used criteria are unclear. Objective:To examine associations of GD with maternal glucose metabolism and childhood adiposity 10 to 14 years' postpartum. Design, Setting, and Participants:The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study established associations of glucose levels during pregnancy with perinatal outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers and 4832 children; study visits occurred between February 13, 2013, and December 13, 2016). Exposures:Gestational diabetes was defined post hoc using criteria from the International Association of Diabetes and Pregnancy Study Groups consisting of 1 or more of the following 75-g oral glucose tolerance test results (fasting plasma glucose ?92 mg/dL; 1-hour plasma glucose level ?180 mg/dL; 2-hour plasma glucose level ?153 mg/dL). Main Outcomes and Measures:Primary maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes or prediabetes). Primary outcome for children: being overweight or obese; secondary outcomes: obesity, body fat percentage, waist circumference, and sum of skinfolds (>85th percentile for latter 3 outcomes). Results:The analytic cohort included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was 11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall and by 14.1% (683/4832) of mothers of participating children. Among mothers with GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1% (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14]; risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers without GD. Adjusted for maternal body mass index during pregnancy, the OR was 1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD was 3.7% (95% CI, -0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was 1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI, 0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to 1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%). Conclusions and Relevance:Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.

Dataset Information

Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids.

Publications

Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids.

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