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Microvesicles Correlated with Components of Metabolic Syndrome in Men with Type 2 Diabetes Mellitus and Lowered Testosterone Levels But Were Unaltered by Testosterone Therapy.

ABSTRACT: Aims. To investigate how circulating microvesicle phenotypes correlate with insulin sensitivity, body composition, plasma lipids, and hepatic fat accumulation. We hypothesized that changes elicited by testosterone replacement therapy are reflected in levels of microvesicles. Methods. Thirty-nine type 2 diabetic males with lowered testosterone levels were assigned to either testosterone replacement therapy or placebo and evaluated at baseline and after 24 weeks. Microvesicles were analysed by flow cytometry and defined as lactadherin-binding particles within the 0.1-1.0??m gate. Microvesicles of platelet, monocyte, and endothelial cell origin were identified by cell-specific markers and their expression of CD36 was investigated. Results. Triglycerides correlated positively with all investigated microvesicle phenotypes in this study (p < 0.05), and indicators of hepatic fat accumulation, alanine aminotransferase, and gamma glutamyltransferase correlated with platelet and endothelial microvesicles and CD36-expressing microvesicles from platelets and monocytes (p < 0.05). BMI, waist circumference, and fat percentage correlated with CD36-expressing monocyte microvesicles (p < 0.05), while insulin sensitivity did not correlate with any microvesicle phenotypes. Microvesicle levels were unaffected by testosterone therapy. Conclusions. Metabolic syndrome components and hepatic fat accumulation correlated with microvesicle phenotypes, supporting the involvement of especially CD36 on monocytes in metabolic syndrome pathogenesis. Although testosterone therapy improved body composition measures, microvesicle phenotype levels were unaffected. This trial was registered at ClinicalTrials.gov (NCT01560546).

SUBMITTER: Botha J

PROVIDER: S-EPMC5266820 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Microvesicles Correlated with Components of Metabolic Syndrome in Men with Type 2 Diabetes Mellitus and Lowered Testosterone Levels But Were Unaltered by Testosterone Therapy.

Botha Jaco J Velling Magnussen Line L Nielsen Morten Hjuler MH Nielsen Tine Bo TB Højlund Kurt K Andersen Marianne Skovsager MS Handberg Aase A

Journal of diabetes research 20170112

<i>Aims.</i> To investigate how circulating microvesicle phenotypes correlate with insulin sensitivity, body composition, plasma lipids, and hepatic fat accumulation. We hypothesized that changes elicited by testosterone replacement therapy are reflected in levels of microvesicles. <i>Methods.</i> Thirty-nine type 2 diabetic males with lowered testosterone levels were assigned to either testosterone replacement therapy or placebo and evaluated at baseline and after 24 weeks. Microvesicles were a ...[more]

PMID: 28168203

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Project description:BackgroundHypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD).Study designRetrospective, cohort study.Setting & participants2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH.PredictorsTotal testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL).OutcomesFactors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves.ResultsHypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16).LimitationsSingle-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias.ConclusionsLow total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.

Dataset Information

Microvesicles Correlated with Components of Metabolic Syndrome in Men with Type 2 Diabetes Mellitus and Lowered Testosterone Levels But Were Unaltered by Testosterone Therapy.

Publications

Microvesicles Correlated with Components of Metabolic Syndrome in Men with Type 2 Diabetes Mellitus and Lowered Testosterone Levels But Were Unaltered by Testosterone Therapy.

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