Rosiglitazone influences adipose tissue distribution without deleterious impact on heart rate variability in coronary heart disease patients with type 2 diabetes

IntroductionObesity is associated with decreased heart rate variability (HRV). Rosiglitazone, a PPARγ agonist, is generally associated with increases in body mass.PurposeTo assess whether the gain in body mass and adiposity expected from rosiglitazone treatment has an influence on HRV in patients with type 2 diabetes and coronary artery disease.MethodsOne hundred and twenty-five patients with type 2 diabetes and coronary artery disease aged between 40 and 75 years were studied. Anthropometric measurements: (1) body mass index (BMI), (2) waist circumference (WC), (3) abdominal computed tomography (CT) scan, and HRV (using a 24 h Holter) were measured at baseline and after 12 months of treatment. Patients were randomized to rosiglitazone or placebo regimen.ResultsIn the rosiglitazone vs. placebo group, there were significant increases in body mass [3.5 (2.6;4.4); mean (95 % CI) vs. 0.2 (−0.4;0.8)] kg), BMI [1.3 (1.0;1.6) vs. 0.1 (−0.1;0.3) kg/m2], WC [2.1 (0.9;3.3) vs. 0.4 (−0.4;1.2) cm, all p ≤ 0.001] and subcutaneous adipose tissue [253 (187;319) vs. 6 (−24;36) cm3, p ≤ 0.001] without statistically significant changes in visceral adipose tissue [−22 (−91;47) vs. 57 (43;71) cm3, p = 0.546], respectively. There was no change in HRV in either group after 12 months. There were no correlations between changes in HRV variables and fat distribution.ConclusionOur results suggest that changes in adiposity indices observed after 12 months of rosiglitazone therapy have no deleterious influence on HRV in patients with type 2 diabetes and coronary artery disease.

[1]  M. Dumont,et al.  Is the relationship between adipose tissue and waist girth altered by weight loss in obese men? , 2001, Obesity research.

[2]  B. Boyer,et al.  Relationships between plasma adiponectin and body fat distribution, insulin sensitivity, and plasma lipoproteins in Alaskan Yup'ik Eskimos: the Center for Alaska Native Health Research study. , 2009, Metabolism: clinical and experimental.

[3]  Jarett D. Berry,et al.  Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults , 2012, Obesity.

[4]  O. Dekkers,et al.  Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: meta-analysis and dose-response meta-regression. , 2013, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[5]  A. Alwan.  Global status report on noncommunicable diseases 2010. , 2011 .

[6]  C. Kahn,et al.  Unraveling the mechanism of action of thiazolidinediones. , 2000, The Journal of clinical investigation.

[7]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[8]  Y. Terauchi,et al.  The Mechanisms by Which Both Heterozygous Peroxisome Proliferator-activated Receptor γ (PPARγ) Deficiency and PPARγ Agonist Improve Insulin Resistance* , 2001, The Journal of Biological Chemistry.

[9]  A. Balasubramanyam,et al.  Thiazolidinediones: a review of their mechanisms of insulin sensitization, therapeutic potential, clinical efficacy, and tolerability. , 2004, Diabetes technology & therapeutics.

[10]  Philippe Pibarot,et al.  Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[11]  J. Després,et al.  Influence of obesity indices, metabolic parameters and age on cardiac autonomic function in abdominally obese men. , 2012, Metabolism: clinical and experimental.

[12]  R. Heine,et al.  Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. , 2003, Drugs.

[13]  V. Rovella,et al.  Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity , 2013, International journal of endocrinology.

[14]  André Tchernof,et al.  Pathophysiology of human visceral obesity: an update. , 2013, Physiological reviews.

[15]  H. Lebovitz,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Rosiglitazone Monotherapy Is Effective in Patients with Type 2 Diabetes , 1999 .

[16]  Y. Terauchi,et al.  The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. , 2001, The Journal of biological chemistry.

[17]  Y. Saijo,et al.  Relationship between C‐reactive protein and visceral adipose tissue in healthy Japanese subjects , 2004, Diabetes, obesity & metabolism.

[18]  Walter C Willett,et al.  Comparison of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes among men. , 2005, The American journal of clinical nutrition.

[19]  J. Després,et al.  Visceral Obesity: The Link Among Inflammation, Hypertension, and Cardiovascular Disease , 2009, Hypertension.

[20]  Pamela Katz,et al.  Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. , 2018, Canadian journal of diabetes.

[21]  Takeshi Tanigawa,et al.  Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study , 2014, Journal of epidemiology.

[22]  L. Ferrucci,et al.  The Relationship between Heart Rate Variability and Adiposity Differs for Central and Overall Adiposity , 2012, Journal of obesity.

[23]  Thomas D. Giles,et al.  Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[24]  S. Mudaliar,et al.  Pioglitazone: side effect and safety profile , 2010, Expert opinion on drug safety.

[25]  H. Crijns,et al.  Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment. , 1994, British heart journal.

[26]  P. Raskin,et al.  Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with Type II diabetes , 2000, Diabetologia.

[27]  M. Jensen,et al.  Lipolysis: contribution from regional fat. , 1997, Annual review of nutrition.

[28]  J. Després,et al.  Impact of visceral obesity on cardiac parasympathetic activity in type 2 diabetics after coronary artery bypass graft surgery , 2013, Obesity.

[29]  J. Dixon,et al.  A randomized controlled trial of the effects of pioglitazone treatment on sympathetic nervous system activity and cardiovascular function in obese subjects with metabolic syndrome. , 2014, The Journal of clinical endocrinology and metabolism.

[30]  J. Després,et al.  A multicentre, randomized, double-blind placebo-controlled trial evaluating rosiglitazone for the prevention of atherosclerosis progression after coronary artery bypass graft surgery in patients with type 2 diabetes. Design and rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after b , 2009, The Canadian journal of cardiology.

[31]  C. Bouchard,et al.  Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements , 1989, British Journal of Nutrition.