Obesity in the pathogenesis of chronic disease

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1 Portoroz October 16th 2013 Obesity in the pathogenesis of chronic disease Rocco Barazzoni University of Trieste Department of Medical, Surgical and Health Sciences

2 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%

3 The epidemics

4 The epidemics Metabolic Disease Cancer CHF CKD CVD Infection Surgical Complications Rheumatic Disease

5 OBESITY A PERFECT METABOLIC STORM HORMONES ADIPOKINES + NF-kB OX STRESS INFLAMMATION IKK SUBSTRATES IRS-1 INFLAMMATION + INSULIN RESISTANCE

6 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:

7 CJASN 2007

8 OBESITY LEADS TO CHF Lavie et al, JACC 2009

9 OBESITY and CANCER

10 CHRONIC DISEASE and Nutritional Status: IMPACT OF OBESITY

11 CHRONIC DISEASE PERFECT METABOLIC STORMS DISEASE OX STRESS INFLAMMATION COMPLICATIONS + IKK NF-kB INFLAMMATION + IRS-1 INSULIN RESISTANCE

12 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

13 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

14 Chronic Disease CALORIC INTAKE Muscle CATABOLISM + RESTING EE = / Muscle Mass Survival

15 Chronic Disease Muscle CALORIC INTAKE INACTIVITY CATABOLISM + RESTING EE = / Muscle Mass Survival

16 Malnutrition Higher care needs and costs Guest J et al, Clin Nutr 2011; 30: 422-9

17 Nutritional treatment: Effective! Underimplemented!!

18 OBESITY A PERFECT METABOLIC STORM HORMONES ADIPOKINES + NF-kB OX STRESS INFLAMMATION IKK SUBSTRATES IRS-1 INFLAMMATION + INSULIN RESISTANCE

19 Obesity leads to higher chance of disability than other major disease risk factors Klijs et al, BMC Pub Health 2011

20 Chronic Disease CALORIC INTAKE INACTIVITY Muscle CATABOLISM + RESTING EE = / Muscle Mass Fat Mass Survival

21 Chronic Disease CALORIC INTAKE INACTIVITY Muscle CATABOLISM + RESTING EE = / Muscle Mass SARCOPENIC Fat Mass OBESITY Survival

22 Sarcopenic Obesity and SURVIVAL!!

23 OBESITY PARADOX and REVERSE EPIDEMIOLOGY in Chronic Disease?

24 Reverse Epidemiology BMI Survival Survival Massa Grassa Johansen et al, Am J Clin Nutr 2004 Lavie et al, JACC 2009

25 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

26 Cardiorespiratory fitness: a relevant confounding factor? McAuley et al, Mayo Clin Proc 2012

27 Cardiorespiratory fitness: a relevant confounding factor? Kramer et al, Am J Kidney Disease 2011

28 Nutritional STRATEGIES

29 Wong et al, Nutr Rev 2011 Am J Clin Nutr 2005

30 Mediterranean Diet and risk of Metabolic Syndrome Metabolic Syndrome Obesity Lipids Glucose Blood Pressure Kastorini et al, JACC 2011

31 Obesity and disease progression: Weight Loss improves renal function parameters in Obese Pre-Dialysys CKD patients Navaneethan et al, CJASN 2009

32 Cardiorespiratory fitness: a relevant confounding factor? Lifestyle/Weight Loss for CRF? McAuley et al, Mayo Clin Proc 2012

33 Preserve MUSCLE Promote ANABOLISM

34 CHRONIC DISEASE PERFECT (METABOLIC) STORMS ANABOLIC + IKK NF-kB IRS-1 RESISTANCE + PROTEIN DEGRADATION OX STRESS INFLAMMATION Reach the INSULIN RESISTANCE (ANABOLIC) threshold

35 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)

36 Oxidative Stress Calorie Intake Inflammation REE Muscle-Adipose T. Insulin Lean Mass Resistance Fat Mass ANABOLIC RESISTANCE

37 Nutraceutical approach? Ann Surg 2009 Clin Nutr 2012 Eur J Nutr 2013

38 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

39 Chronic Disease Immobilization Reduced mobilization Chronic Disease CALORIC INTAKE Exercise Muscle CATABOLISM + RESTING EE = / Muscle Mass Survival

40 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.

41 Thank you for your attention

42

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