Portoroz October 16th 2013 Obesity in the pathogenesis of chronic disease Rocco Barazzoni University of Trieste Department of Medical, Surgical and Health Sciences
Obesity Trends* Among U.S. Adults BRFSS, 2010 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%
The epidemics
The epidemics Metabolic Disease Cancer CHF CKD CVD Infection Surgical Complications Rheumatic Disease
OBESITY A PERFECT METABOLIC STORM HORMONES ADIPOKINES + NF-kB OX STRESS INFLAMMATION IKK SUBSTRATES IRS-1 INFLAMMATION + INSULIN RESISTANCE
Abdominal Obesity Hypertension Dysglycemia Dyslipidemia Metabolic Syndrome CV Risk MI Stroke Measure Elevated waist circumference Elevated blood pressure* Elevated fasting glucose* Elevated triglycerides* Reduced HDL-c* Categorical cut points >94 cm in males >80 cm in females Systolic > 130 and/or diastolic > 85 mm Hg > 100 mg/dl > 150 mg/dl (1.7 mmol/l) < 40 mg/dl (1.0 mmol/l) in males; < 50 mg/dl (1.3 mmol/l) in females Alberti KGMM, et al. Circulation 2009; 120: 1640-5.
CJASN 2007
OBESITY LEADS TO CHF Lavie et al, JACC 2009
OBESITY and CANCER
CHRONIC DISEASE and Nutritional Status: IMPACT OF OBESITY
CHRONIC DISEASE PERFECT METABOLIC STORMS DISEASE OX STRESS INFLAMMATION COMPLICATIONS + IKK NF-kB INFLAMMATION + IRS-1 INSULIN RESISTANCE
CAUSES of MUSCLE LOSS in Chronic Kidney Disease -Genetics -Cause of CKD Obesity Diabetes -Toxins -Acidosis -Infections -Endocrine (GH,T) -Oxidative Stress -Inflammation + -Inactivity -Anorexia Muscle PROTEIN CATABOLISM
CAUSES of MUSCLE LOSS in Chronic Kidney Disease -Genetic -Cause of CKD Obesity Diabetes Dyalisis -Oxidative Stress -Inflammation -Nutrient loss + - Inactivity - Anorexia Muscle PROTEIN CATABOLISM
Chronic Disease CALORIC INTAKE Muscle CATABOLISM + RESTING EE = / Muscle Mass Survival
Chronic Disease Muscle CALORIC INTAKE INACTIVITY CATABOLISM + RESTING EE = / Muscle Mass Survival
Malnutrition Higher care needs and costs Guest J et al, Clin Nutr 2011; 30: 422-9
Nutritional treatment: Effective! Underimplemented!!
OBESITY A PERFECT METABOLIC STORM HORMONES ADIPOKINES + NF-kB OX STRESS INFLAMMATION IKK SUBSTRATES IRS-1 INFLAMMATION + INSULIN RESISTANCE
Obesity leads to higher chance of disability than other major disease risk factors Klijs et al, BMC Pub Health 2011
Chronic Disease CALORIC INTAKE INACTIVITY Muscle CATABOLISM + RESTING EE = / Muscle Mass Fat Mass Survival
Chronic Disease CALORIC INTAKE INACTIVITY Muscle CATABOLISM + RESTING EE = / Muscle Mass SARCOPENIC Fat Mass OBESITY Survival
Sarcopenic Obesity and SURVIVAL!!
OBESITY PARADOX and REVERSE EPIDEMIOLOGY in Chronic Disease?
Reverse Epidemiology BMI Survival Survival Massa Grassa Johansen et al, Am J Clin Nutr 2004 Lavie et al, JACC 2009
Which obese patients may BENEFIT? ONE size does NOT fit all HIGH BMI HIGH WC (ABDOMINAL OBESITY) Kramer et al, Am J Kidney Disease 2011
Cardiorespiratory fitness: a relevant confounding factor? McAuley et al, Mayo Clin Proc 2012
Cardiorespiratory fitness: a relevant confounding factor? Kramer et al, Am J Kidney Disease 2011
Nutritional STRATEGIES
Wong et al, Nutr Rev 2011 Am J Clin Nutr 2005
Mediterranean Diet and risk of Metabolic Syndrome Metabolic Syndrome Obesity Lipids Glucose Blood Pressure Kastorini et al, JACC 2011
Obesity and disease progression: Weight Loss improves renal function parameters in Obese Pre-Dialysys CKD patients Navaneethan et al, CJASN 2009
Cardiorespiratory fitness: a relevant confounding factor? Lifestyle/Weight Loss for CRF? McAuley et al, Mayo Clin Proc 2012
Preserve MUSCLE Promote ANABOLISM
CHRONIC DISEASE PERFECT (METABOLIC) STORMS ANABOLIC + IKK NF-kB IRS-1 RESISTANCE + PROTEIN DEGRADATION OX STRESS INFLAMMATION Reach the INSULIN RESISTANCE (ANABOLIC) threshold
Dietary PROTEIN: Strategies for optimal muscle anabolism Protein DISTRIBUTION Paddon-Jones et al, Curr Op Clin Nutr Metab Care 2009 Protein DIGESTION-Availability (FAST-SLOW)
Oxidative Stress Calorie Intake Inflammation REE Muscle-Adipose T. Insulin Lean Mass Resistance Fat Mass ANABOLIC RESISTANCE
Nutraceutical approach? Ann Surg 2009 Clin Nutr 2012 Eur J Nutr 2013
TREATMENT for ENERGY METABOLISM AND ATP Production Amino Acids? Barazzoni et al Am J Physiol Endocrinol Metab 2012 D Antona et al, Cell Metab 2011
Chronic Disease Immobilization Reduced mobilization Chronic Disease CALORIC INTAKE Exercise Muscle CATABOLISM + RESTING EE = / Muscle Mass Survival
Conclusions Obesity is a major risk factor for chronic metabolic disease and chronic organ failure, associated with substantial clinical burden. Obesity may negatively modulate metabolic and nutritional status of chronic disease patients, with negative impact on outcome. Reported improved outcome in obese patient subgroups with chronic disease may reflect the impact of better nutritional status (absence of malnutrition) but more studies are needed to determine risk stratification in patients with metabolic and cardiovasular complications (abdominal fat, CRF). Nutritional intervention to enhance muscle anabolism and lean body mass is potentially lifesaving in both non-obese and obese patients with chronic disease.
Thank you for your attention