title: Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Rovira-Llopis
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Aranzazu M
authors.initials: AM
authors.lastname: de Marañon
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Diaz-Morales
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Jover
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Garzon
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, Department of Pharmacology, University of Valencia, Valencia, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, Department of Pharmacology, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain. Electronic address: victor.victor@uv.es.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
authors.affiliation: Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain. Electronic address: hernandez_antmij@gva.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez-Mijares
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk; D013739:Testosterone / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D013739:Testosterone
keywords: Cardiovascular risk; Leukocytes; Mitochondria; Testosterone; Type 2 diabetes