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Diabetes obesity in patients with COPD Angelo Avogaro

Atherogenic dyslipidemia  Triglycerides  HDL-cholesterol  Cholesterol/HDL-cholesterol ratio "Normal" LDL-cholesterol but  apo B Small, dense LDL and HDL Postprandial hyperlipidemia Insulin resistance Hyperinsulinemia Hyperglycemia Type 2 diabetes Thrombotic state  PAI-1  Fibrinogen Inflammatory state  CRP  Cytokines  risk of acute coronary syndrome Metabolic risk factorsAbdominal obesity Inflammation Lipid core Thin fibrous cap CORONARY ATHEROSCLEROSIS UNSTABLE PLAQUE Intra-abdominal Obesity, Metabolic Risk Factors and CHD adapted from Despres, 2004

Adverse cardiometabolic effects of products of adipocytes Adipose tissue ↑ IL-6 ↓ Adiponectin ↑ Leptin ↑ TNF α ↑ Adipsin (Complement D) ↑ Plasminogen activator inhibitor-1 (PAI-1) ↑ Resistin ↑ FFA ↑ Insulin ↑ Agiotensinogen ↑ Lipoprotein lipase ↑ Lactate Inflammation Type 2 diabetes Hypertension Atherogenic dyslipidaemia Thrombosis Atherosclerosis Lyon 2003; Trayhurn et al 2004; Eckel et al 2005

2001

COPD Inflammation May Contribute to Cardiovascular Disease Rennard. Proc Am Thorac Soc. 2005;2:

38 COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16% 34 control participants matched for age and gender are included in this study. RESULTS: 47% of COPD patients and 21% of control participants presented metabolic syndrome. CONCLUSIONS: The presence of metabolic syndrome is frequent in patients with COPD who participated in a cardiopulmonary program. Hence, this population should be considered for screening for the metabolic syndrome. Marquis K et al, J Cardiopulm Rehabil The metabolic syndrome in patients with chronic obstructive pulmonary disease

Peak YJ at al, Metabolism 2010

Log-transformed (log) hs-CRP (A), log interleukin-6 (B), fibrinogen (C), and physical activity level (D) according to GOLD stages and the absence or presence of the metabolic syndrome. Watz H et al. Chest 2009;136:

11 Visceral adipose tissue favours systemic inflammation Visceral tissue area (cm 2 ) Waist girth (cm) , ,2 1,2,3 Quintiles of PCR (1)(2)(3)(4)(5)(1)(2)(3)(4)(5) Lemieux I et al. Arterioscler Thromb Vasc Biol 2001;21: Quintiles of PCR

Sleep Disorders-Metabolic Syndrome Sleep Fragmentation Sleep Deprivation Intermittent Hypoxemia Increased Sympathetic Drive Sleep Disorders Metabolic Syndrome

Homeostasis model assessment in Respiratory Distress Syndrome Punjabi, N. M. et al. Am. J. Epidemiol : ; doi: /aje/kwh26

van Buul, J. D. et al. Arterioscler Thromb Vasc Biol 2004;24: Schematic overview of the distinct steps that comprise leukocyte transendothelial migration

Cardiovascular Health Risk Factors Rescue Factors HDL cholesterol Anti oxidant reserves Endothelial progenitor cells Cigarette smoking Diabetes Mellitus Hypercholesterolemia Hypertension Obesity Age Family history of CVD Gender Postprandial Hyperglycemia

Risk factors Apoptosis Regeneration EPC Endothelial cell apoptosis and -regeneration

The biological significance of EPCs What they are? The biological significance of EPCs What they are? Fadini et al, Diabetes Care 2007

The clinical significance of EPCs Disease Marker – Cardiovascular risk The clinical significance of EPCs Disease Marker – Cardiovascular risk Fadini et al. Eur Heart J 2006 Fadini et al. ATVB 2006

The clinical significance of EPCs Disease Marker – Pulmonary diseases The clinical significance of EPCs Disease Marker – Pulmonary diseases Fadini et al. Stem Cells 2006 COPD RLD

The clinical significance of EPCs Disease Marker – CVD vs Pulmonary disease The clinical significance of EPCs Disease Marker – CVD vs Pulmonary disease Fadini et al. AJRCMB 2006

Fadini et al. Eur Respir J. 2010