Clinical Nutrition in the 21st Century Malnutrition, sarcopenia and cachexia

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1 Clinical Nutrition in the 21st Century Malnutrition, sarcopenia and cachexia Stéphane M. Schneider, MD, PhD, FEBGH Professor of Nutrition and ESPEN ECPC Chair

2 In proto-indo-european, Latin and Greek Under (lower) nutritio (to feed oneself) Sarcos (flesh) penia (poverty) Kakos (bad) hexis (condition) Malnutrition, emaciation, inanition, deassimilation, cacotrophy, myopenia, dynapenia, kratopenia

3 (Protein-Energy) Undernutrition A type of malnutrition caused by inadequate food intake or the body's inability to make use of needed nutrients. Undernutrition is a state of nutrition in which a deficiency of energy, protein, and other nutrients causes measurable adverse effects on tissue/body form (body shape, size and composition) and function, and clinical outcome. Stratton et al. Cabi 2003

4 (Protein-Energy) Undernutrition ICD-10

5 PEU: a continuum Marasmus Kwashiorkor Pathophysiological continuum Normal albuminemia Hypoalbuminemia, edema Balanced PEU Physiological adaptation Protein loss Metabolic stress From J.C. Melchior

6 Nutritional disorders Cederholm et al. Clin Nutr 2015

7 Cruz-Jentoft et al. Age Ageing yrs Sarcopenia Sarcopenia is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death. 56 yrs 73 yrs 85 yrs

8 Sarcopenia: a geriatric syndrome Cruz-Jentoft et al. Curr Op Clin Nutr Metabol 2010

9 Cachexia Cachexia may be defined as a multifactorial syndrome characterized by severe body weight, fat and muscle loss and increased protein catabolism due to underlying disease(s). Cachexia is clinically relevant since it increases patients morbidity and mortality. Contributory factors to the onset of cachexia are anorexia and metabolic alterations, i.e. increased inflammatory status, increased muscle proteolysis, impaired carbohydrate, protein and lipid metabolism. Muscaritoli et al. Clin Nutr 2008

11 Baumgartner et al. Am J Epidemiol 1998 First definition of sarcopenia Sarcopenia Normal M : < 7.26 kg/m 2 F : < 5.45 kg/m 2-2 SD Mean Appendicular skeletal muscle (kg/m 2 )

12 Body composition BMI = 25 Muscle = 46.7 kg Fat = 21.3 kg BMI = 24.7 Muscle = 31.8 kg Fat = 20.5 kg Antoun and Baracos

13 Survival of obese cancer patients according to their muscle mass HR 4.2 [ ], p<0.0001) Prado et al. Lancet Oncol 2008

2 yrs) and 1997-98 Muscle strength (leg press) Cross sectional area (computed tomography)

14 Muscle work (J) Evolution of muscle strength and thigh muscle cross sectional area between ages 65 and %/yr %/yr Nine healthy subjects assessed in (age 65.4 ± 4.2 yrs) and Muscle strength (leg press) Cross sectional area (computed tomography) Knee extensors work (25 contractions) Thigh muscle area Frontera et al. J Appl Physiol 2000

15 HGS as a predictor of functional, psychological and social health Taekema et al. Age Ageing 2010

16 EWGSOP criteria for sarcopenia - adopted by EUGMS/ESPEN/IAGG/IANA Reduced muscle mass 2 SD below mean of muscle mass in a young ref population Appendicular lean mass < 5.7 kg/m 2 (F) < 7.2 kg/m 2 (M) + Impaired muscle function 4 m walking speed < 0.8 m/sec or reduced grip strength 20 kg (F), 30 kg (M) Cruz-Jentoft et al. Age Ageing 2010

17 Cachexia Weight loss 5% in 12 months (or BMI< 20) and chronic disease + at least three of the five following criteria: Reduced muscle strength (lowest tertile) Fatigue Anorexia (< 70 % usual food intake, < 20 kcal/kg/d, VAS ) Low fat-free mass index (MAMC < 10 th percentile, DXA according to Baumgartner) Abnormal biochemistry Inflammation (CRP > 5) / anemia (< 12) / hypoalbuminemia (< 32) Evans et al. Clin Nutr 2008

18 Cancer cachexia Involuntary weight loss > 5% over 6 months or BMI < 20 and weight loss > 2% or Sarcopenia : appendicular skeletal muscle mass (M < 7.26 kg/m 2, F < 5.45) or mid-arm muscle circumference (M < 32 cm, F < 18) or CT-scan lumbar muscle surface (M < 55 cm 2 /m 2, F < 39) or BIA FFM (H < 14.6 kg/m2, F < 11.4) and weight loss > 2% Do not take body weight into account in case of water retention, large tumour mass, overweight/obesity. Fearon et al. Lancet Oncol 2011

19 Precachexia Underlying chronic disease, Unintentional weight loss 5% of usual body weight during the last 6 months, Anorexia or anorexia-related symptoms, Chronic or recurrent systemic inflammatory response. All criteria must be fulfilled Muscaritoli et al. Clin Nutr 2010

20 Why an early diagnosis? Fearon et al. Lancet Oncol 2011

21 Malnutrition thresholds in older patients Raynaud-Simon et al. Clin Nutr 2010

22 Problems with the current situation No gold standard Mix between screening and diagnosis Huge differences in prevalence Lack of recognition Lack of financing

24 What experts want Meijers et al. Nutrition 2010

ASPEN/AND consensus statement Because no single parameter is definitive for adult malnutrition, the identification of 2 or more of the following 6 characteristics is recommended for diagnosis:

25 ASPEN/AND consensus statement Because no single parameter is definitive for adult malnutrition, the identification of 2 or more of the following 6 characteristics is recommended for diagnosis: Insufficient energy intake Weight loss Loss of muscle mass Loss of subcutaneous fat Still no cut-offs! Localized or generalized fluid accumulation that may sometimes mask weight loss Diminished functional status as measured by handgrip strength White et al. JPEN 2012

26 Diagnostic criteria for malnutrition Step 1. Risk screening by a validated instrument, e.g. NRS2002, MUST, MST, MNA(-SF),... i.e. BMI, Weight loss, Reduced food intake, Disease severity Step 2. Diagnosis BMI <18.5 kg/m 2 Alternative diagnostic trajectory Weight loss >10% (indefinite time)/>5% last 3 mo combined with either BMI <20 (if <70 years)/<22 (if >70 y) or FFMI <15 and 17 kg/m 2 in women and men, respect. Cederholm et al. Clin Nutr 2015

27 Differential diagnosis Starvation (young) Starvation (old) Metabolic stress Agerelated sarcopenia Cachexia Appetite Inflammation Body weight Muscle mass Muscle strength Fat mass Blood markers - (Alb) Alb, CRP CAF CRP, Alb Prognosis Treatment Nut Nut (Nut) Resistance AI

28 260 subjects, 87 ± 5 yrs RR = 3.45 ( ) Landi et al. Clin Nutr 2012

29 Rheumatoid cachexia: a disappointing definition However, nearly all patients were in the lowest tertile for HGS van der Schueren et al. Clin Nutr 2012

35 A black hole

36 Conclusions Semantics are crucial as they allow communication, comparisons and common initiatives. The ideal definitions need to : Have a prognostic value Integrate mechanisms (for therapeutic purposes) Address the main body compartments (body composition) Be sensitive to interventions What s next? Validation studies!!!

37 A possible consensus? Malnutrition diagnosed (ESPEN) White et al. JPEN 2012, Jensen et al. JPEN 2012

38 I am not sure So? Malnourished, sarcopenic, cachectic?

ESPEN Congress Copenhagen 2016

ESPEN Congress Copenhagen 2016 THE DIVERSITY OF OBESITY MALNUTRITION IN THE OBESE R. Barazzoni (IT) Malnutrition in the obese patient Rocco Barazzoni Dept of Medical, Surgical and Health Sciences University