Susana Rovira-Llopis1, Celia Bañuls1, Aranzazu M de Marañon1, Noelia Diaz-Morales1, Ana Jover1, Sandra Garzon1, Milagros Rocha2, Victor M Victor3, Antonio Hernandez-Mijares4. 1. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain. 2. 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. 3. 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. 4. 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.
Abstract
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.
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 diabeticpatients. MATERIALS AND METHODS: The study was performed in 280 male type 2 diabeticpatients 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 diabeticpatients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabeticpatients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabeticpatients, 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 diabeticmen 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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