Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients

Free Radic Biol Med. 2017 Jul;108:155-162. doi: 10.1016/j.freeradbiomed.2017.03.029. Epub 2017 Mar 27.


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, TNFα, 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. 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.

Keywords: Cardiovascular risk; Leukocytes; Mitochondria; Testosterone; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / complications
  • Atherosclerosis / diagnosis
  • Atherosclerosis / metabolism*
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes / physiology*
  • Male
  • Membrane Potential, Mitochondrial
  • Middle Aged
  • Mitochondria / metabolism*
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Risk
  • Testosterone / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Vascular Cell Adhesion Molecule-1
  • Testosterone