Sjukdoms- vs. svältrelaterad undernäring - malnutrition ur etiologiskt perspektiv Tommy Cederholm Professor, Klinisk nutrition och metabolism, Folkhälsooch vårdvetenskap, Uppsala Universitet Överläkare, Geriatriska kliniken, Akademiska sjukhuset, Uppsala Catabolic trajectories leading to disability & death Robust & Healthy Cachexia, sarcopenia and frailty are risk factors for disability and death † Kakexi = Sjukdoms-relaterad malnutrition (DRM) med inflammation - Sjukdom - Viktförlust >5% s. 12 m eller - BMI<20 + ≥3 av - Minskad muskelstyrka - Minskad muskelmassa - Trötthet - Anorexi - CRP/albumin/anemi Evans et al. Clin Nutr 2008 - Sjukdom - Viktförlust >5% 3m/10% och - BMI<20/22 (<70/>70 år) eller - Minskad muskelmassa - CRP/albumin ESPEN Consensus. Clin Nutr 2015 Current challenges The nutrition community needs - clinically relevant aetiology-based diagnoses of malnutrition (to be used for the ICD and other classification systems) - diagnostic criteria for malnutrition Etiology-based defintions General mechanisms underlying malnutrition/undernutrition • Food deprivation/starvation – due to poverty, natural disaster; floodings, droughts • Catabolic disease with inflammation and anorexia • Disease with non-inflammatory reasons for reduced food intake or absorption Todays diagnostic procedures of malnutrition don’t take aetiology into consideration ESPEN Guidelines on Definitions and Terminology Malnutrition diagnoses tree Risk screening Basic diagnosis Etiology-based diagnoses At risk for malnutrition Malnutrition/Undernutrition Disease-related malnutrition (DRM) with inflammation Acute disease- or injury-related malnutrition Disease-related malnutrition (DRM) without inflammation Chronic DRM with inflammation Malnutrition/Undernutrition without disease Socioeconomic or psychologic related malnutrition Hunger-related malnutrition Cancer cachexia and other disease-specific cachexia ESPENCederholm Consensus 2016 et al. Statement Clin Nutr 2016;e-pub ESPEN Guidelines on Definitions and Terminology Malnutrition diagnoses tree Risk screening Basic diagnosis Etiology-based diagnoses At risk for malnutrition Malnutrition/Undernutrition Disease-related malnutrition (DRM) with inflammation Acute disease- or injury-related malnutrition Disease-related malnutrition (DRM) without inflammation Chronic DRM with inflammation Malnutrition/Undernutrition without disease Socioeconomic or psychologic related malnutrition Hunger-related malnutrition Cancer cachexia and other disease-specific cachexia ESPENCederholm Consensus 2016 et al. Statement Clin Nutr 2016;e-pub Malnutrition or undernutrition? ESPEN membership ballot >300 votes: 53% malnutrition 47% undernutrition More consideration is needed ESPEN Guidelines on Definitions and Terminology Malnutrition diagnoses tree Risk screening Basic diagnosis Etiology-based diagnoses At risk for malnutrition Malnutrition/Undernutrition Disease-related malnutrition (DRM) with inflammation Acute disease- or injury-related malnutrition Malnutrition/Undernutrition Disease-related malnutrition Malnutrition related to without disease (DRM) without inflammation Chronic DRM with inflammation Cancer cachexia and other disease-specific cachexia - Cancer Socioeconomic or COPD psychologic related Congestive heart failue malnutrition Infections Trauma ICU Hunger-related malnutrition ESPENCederholm Consensus 2016 et al. Statement Clin Nutr 2016;e-pub Inflammation och kakexi/KOL 70 S-TNF (pg/ml) 60 50 (16) 40 30 p<0.05 20 10 (14) 0 COPD/PEM COPD Controls Di Francia Am J Respir Crit Care Med 1994;150:1453-5 Disease/trauma/aging Inflammation Neuropeptid Y↓ Leptin↑ Anorexia Insulin resistence Hormon sensitive lipase↑ Cathepsin↑ Ubiquitin-proteasom↑ Proteolysis Lipoprotein lipase Lipolysis Cachexia → Sarcopenia Inflammation och muskelnedbrytning insulin TNFa IL-1b protein Insulin resistance + Sarkopeni + ubiquitine nucleus proteasome Amino acids - alanine - glutamine Oliff 1987 gluconeogenesis gut immune system Muskel... • • • • • • • • • • ~40% av kroppsvikten ~20% av muskeln är protein 50-75% av kroppens protein Rörlighet Styrka Aminosyrapool Glukosreglering Energiomsättning Endokrina funktioner .... Weight as predictor of COPD mortality Survival (%) 100 400 COPD-patients, >65 y 4 y follow-up 80 Independent mortality predictors; • BMI <24 (obesity paradox) 60 40 20 • Age • PaO2 • PaCO2, FEV1, sex BMI>29 BMI 24-29 BMI 20-24 BMI <20 0 12 24 36 48 Months Schols et al. Am J Respir Crit Care Med 1998;157:1791-7 Kardiell- kakexi Kardiell kakexi mortalitet Definition: >6% viktförlust s. 6 mån Prevalens: 12-15% (NYHA II-IV) Incidens: 10%/år Anker et al. Clin Nutr 2006;25:311 Anker et al. Lancet 2003;361:1077-83 Myrianthefs et al. Cytokine 2007 ESPEN Guidelines on Definitions and Terminology Malnutrition diagnoses tree Risk screening Basic diagnosis Etiology-based diagnoses At risk for malnutrition Malnutrition/Undernutrition Disease-related malnutrition (DRM) with inflammation Acute disease- or injury-related malnutrition Disease-related malnutrition (DRM) without inflammation Chronic DRM withMalnutrition related to inflammation Malnutrition/Undernutrition without disease Socioeconomic or psychologic related malnutrition Hunger-related malnutrition - Stroke, Parkinson - Dementia Cancer cachexia and other - Anorexia nervosa disease-specific cachexia - Depression - Malabsorption ESPEN Consensus Statement 2016 - Coeliac disease - Short bowel syndrome Cederholm et al. Clin Nutr 2016;e-pub ESPEN Guidelines on Definitions and Terminology Malnutrition diagnoses tree Risk screening Basic diagnosis Etiology-based diagnoses At risk for malnutrition Malnutrition/Undernutrition Disease-related malnutrition (DRM) with inflammation Acute disease- or injury-related malnutrition Disease-related malnutrition (DRM) without inflammation Chronic DRM with inflammation Malnutrition/Undernutrition without disease Socioeconomic or psychologic related malnutrition Hunger-related malnutrition Cancer cachexia and other disease-specific cachexia ESPENCederholm Consensus 2016 et al. Statement Clin Nutr 2016;e-pub Kroppsviktens relation till funktion och överlevnad hos hemmaboende äldre ~13.000 >65 år 7 års uppföljning Optimal funktion vid BMI ~25 Högst överlevnad vid BMI ~25-30 Sämst överlevnad vid BMI <22 Bra funktion Al Snih S et al. Arch Intern Med 2007;167:774-80 ”Obesity paradox” ! BMI<22 Överlevnad MAIDS – malnutrition associated immune deficiency syndrome Cell mediated immunity↓ – – • Humoral immunity↓ – • T lymphocytopenia CD4/CD8 ratio↓ Ig-prod↓→Vaccination↓ Granulocyte dysfunction – – Chemotaxis↓ Oxygen radical production↓ Infections Mentala effekter av svält 34 unga män, 1500 kcal/dag 6 mån, förlorade 25% av kv • Depression • Apati • Irritabilitet • Social tillbakadragenhet Depressionsskala 100 50 Svält 0-6 Refeeding 6-15 0 0 6 9 15 Mån Keys A. The Biology of Human Starvation 1950 Next challenge: Define diagnostic criteria for malnutrition/undernutrition The nutrition care process needs to assure a diagnostic procedure • Screening/risk evaluationnutritional risk • Assessment for treatment • Treatment • Monitoring Next challenge: Define diagnostic criteria for malnutrition/undernutrition The nutrition care process needs to assure a diagnostic procedure • Screening/risk evaluationnutritional risk • Assessment for diagnosis and treatment • Diagnosis • Treatment • Monitoring ”…elements important in operationalism of malnutrition were involuntary weight loss, body mass index, and no nutritional intake” Conclusion: This study shows that there is no full agreement among experts on the elements defining malnutrition. The results of this study may fuel the discussion within the nutritional societies, which will most ideally lead to an international consensus on a definition and operationalism of malnutrition. ESPEN initiative 2012-2015 Diagnostic criteria for malnutrition to be • used by physicians in daily clinical practice; • simple; i.e. minimum no. of items – compare Obesity = BMI >30 kg/m2 • adopted by the International Classification of Diseases (ICD-10/11) ESPEN initiative 2012-2015 What is the core of malnutrition? Nutrition indicators considered • • • • • • • • • Weight loss Reduced food intake Reduced appetite Low BMI Reduced lean mass Reduced fat mass Inflammation Subjective evaluation Functional measures ESPEN Working Group: Tommy Cederholm, Ingvar Bosaeus, Rocco Barazzoni, Juergen Bauer, Andre Van Gossum, Stanislaw Klek, Maurizio Muscaritoli, Ibolya Nyulasi, Johann Ochenga, Stéphane Schneider, Marian de van der Schueren, Pierre Singer Cederholm et al. Clin Nutr 2015;34:335-40. ESPEN suggestion for diagnostic criteria for malnutrition Step 1. Risk screening by a validated instrument , e.g. NRS-2002, MUST, MNA(-SF), SNAQ, ... i.e. BMI, Weight loss, Reduced food intake, Disease severity Step 2. Diagnosis is confirmed by • BMI <18.5 kg/m2 or • Weight loss >10% (indefinite time)/>5% last 3 mo combined with either • BMI <20 (<70 y)/<22 (>70 y) or • FFMI <15 and 17 kg/m2 in women and men, respect. Cederholm et al. Clin Nutr 2015;34:335-40. ESPEN Poll - 304 ”votes” Criteria 1 5 10 1=strongly disagree, 2-9= .... 10=strongly agree 26% 8 Result: ~70% ≥ 8/10 agreement Conclusion: ”Strong support” Problems and issues raised that should be considered • Too restrictive cut-offs – Low prevalence figures less reimbursement • How to handle weight loss/malnutrition in obese patients? • Low access to body composition measurement techniques • Lack of criteria indicating pathophysiology • Ethnicity/adapted cut-offs Potential solutions from on-going discussions within the ESPEN community Introduction of a grading system? – At risk for malnutrition (not for ICD) For ICD –Malnutrition stage 1 –Malnutrition stage 2 Grading of malnutrition • At risk for malnutrition (by any validated screening tool) – The diagnosis of malnutrition is only considered after screening positive • Malnutrition stage 1 – – – – • Weight loss (unintentional, 5/10%) and Any etiology; e.g. food intake↓, catabolic disease, malabsorption and BMI >20/22 kg/m2 or FFM > lower cutoff/culture relevant (FFMI >15/17); BC, muscle function Malnutrition stage 2 (similar to ESPEN Diagnostic Criteria 2015) – – – – Weight loss (unintentional, 5/10%) and Any etiology; e.g. food intake↓, catabolic disease, malabsorption and BMI < 20/22 kg/m2 or FFM < lower cutoff/culture relevant (FFMI >15/17); BC, muscle function On-going process since 2016 The Global Leadership Initiative on Malnutrition* (GLIM) Diagnosis and diagnostic criteria of malnutrition *Working Group created with 5-7 delegates from each continental PEN- society: ESPEN, ASPEN, FELANPE and PENSA - A CORE Working Group with 2 delegates each is also created Energi- och proteintillägg halverade dödligheten hos utskrivna sjukhuspatienter – The Nourish Study • • • • 652 undernärda sjukhuspat, >65 år Hjärtsvikt, KOL, AMI, pneumoni RCT: 350 kcal, 20 g prot, 160 IU D-vitamin, 1,5 g HMB x2/placebo 90 dagars behandling Slutsats: Halverad dödlighet efter 3 månaders behandling med kosttillägg; från ~10% till ~5% Deutz et al. Clin Nutr 2016;35:18-26 Metaanalys av proteinrika näringstillskott • • • • • 36 RCT, 3790 patienter (1/3 gamla, 1/3 höftfrakturer) Observationstid 3 mån Högprotein-ONS (>20E%) Färre • Komplikationer • Återinläggningar Förbättrad • Vikt • Greppstyrka Cawood. Aging Res Rev 2012 ONS and re-admission – a meta-analysis • 6 studies (n=852) qualified to be part of the meta-analyses • 23% re-adm by ONS vs 33% in controls (p<0.001) Conclusion: ONS reduced re-admissions by ~40% Stratton et al. Aging Res Rev 2013 Ghrelin-agonist, lungcancer och lean body mass 495 patienter med små-cellig lungcancer och anorexi-kakexi. Ghrelin-agonist under 12 veckor. DXA/lean body mass (kg). Handgreppsstyrka. • LBM↑ • HGS • Symptom Temel et al. Lancet Oncol 2016;17:519-31 Sammanfattning • Sjukdomsrelaterad malnutrition med inflammation – Cancer, KOL, hjärtsvikt, …. • Sjukdomsrelaterad malnutrition utan inflammation – Stroke, Parkinson, demens, depression, …. • Diagnoskriterier för malnutrition? – ESPEN: Viktförlust, BMI, Fettfri massa/muskel, etiologi, – GLIM: Viktförlust, …? • DRM är behandlingsbart – Mat, träning, läkemedel • Att behandla DRM är kostnadseffektivt