Relationship between Low Testosterone Levels, Oxidative Stress, Mitochondrial Dysfunction and Altered Subclinical Atherosclerotic Markers in Type 2 Diabetes

Type 2 diabetes and cardiovascular diseases are related to low testosterone levels. In the present study we have evauated mitochondrial function, leukocyte-endothelium interactions, metabolic parameters and oxidative stress in type 2 diabetic patients and theirrelationship wuth typ2 2 diabetes.

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, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated.
Results: Testosterone levels were decreased in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, 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.

This study was financed by grants PI16/1083, PI16/oo301 and UGP15-193 and by the European Regional Development Fund (ERDF “A way to build Europe”).