Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 108, Issue -, Pages 155-162Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2017.03.029
Keywords
Testosterone; Type 2 diabetes; Cardiovascular risk; Mitochondria; Leukocytes
Funding
- Carlos III Health Institute, Spain [PI15/1424, PI16/1083, PI16/00301]
- FISABIO, Spain [UGP15-193]
- Ministry of Education of the Valencian Regional Government [CIBERehd CB06/04/0071, PROMETEO 2014/035, GV/2016/169]
- European Regional Development Fund (ERDF A way to build Europe)
- Ministry of Health of the Valencian Regional Government [CES10/030]
- Carlos III Health Institute [CPII16/00037, CD14/00043]
- Juan de la Cierva-Formacion contract from the Ministry of Economy and Competitiveness, Spain [FJCI-2015-25040]
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Introduction: Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. Materials and methods: The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNF alpha, adhesion molecules and leukocyte-endothelium cell interactions were evaluated. Results: Testosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFa, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion. Conclusions: Our data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events.
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