X-FILES in NUTRIZIONE CLINICA ed ARTIFICIALE

Transcription

1 Obesità sarcopenica Lorenzo M Donini Dipartimento di Medicina Sperimentale Sezione di Fisiopatologia Medica, Scienza dell Alimentazione ed Endocrinologia Lorenzomaria.donini@uniroma1.it

2 Definizione e fisiopatologia dell obesità sarcopenica

3

4 increased FM is associated with larger thigh muscle but with muscle of different composition than in leaner subjects advancing age and increased obesity are associated with reduced muscle density in older, healthy adults, but the respective effects on muscle size are opposite

5 Greater FM was related to LBM at baseline in men and women muscle strength but significantly muscle quality decline in leg lean mass in both men and women The decline in muscle strength exceeds the decline in muscle mass (Hughes VA et al: J Gerontol Biol Sci. 2001;Lauretani F et al: J Appl Physiol. 2003)

6 Fat has several adverse effects on muscle function: greater intramuscular lipid and reduced muscle quality (reduced strength/cross sectional area) decrease of the capacity to generate power (= force x speed) (muscle power is more closely related to functional capacity than muscle strength).

7 mean muscle attenuation values are a direct measure of reduced muscle density and are associated with an increased lipid accumulation within muscle the attenuation values of muscle on CT can account for differences in muscle strength not attributed to muscle quantity.

8 age-related increase in fatty infiltration of muscle (increase in IMF) IMF of skeletal muscle worsened over 5y regardless of weight and SF changes the decreases in strength were 2 5 times greater than the loss of muscle size weight gain did not attenuate the loss of strength with aging losses in MQ with aging

9 Fat infiltrates skeletal muscle under a host of conditions, including obesity. pluripotent capacity of progenitor cells of myocytes, which can differentiate into other cell types, including adipocytes, in response to various stimuli, such as the denervation of muscle tissue that accompanies aging. insulin resistance

10 Functioning problems may arise as a result of the impairment of: muscle mass and quality anabolic effect of insulin to suppress protein breakdown and stimulate muscle synthesis (Chevalier S et al: Am J Clin Nutr 2005 and J Gerontol A Biol Sci Med Sci 2006; Visser M et al: J Am Geriatr Soc 2002; Goodpaster BH et al: Am J Clin Nutr 2000)

11 After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated proinflammatory cytokines (IL-6, CRP, IL-1 receptor antagonist, soluble IL-6 receptor) global obesity (in particular central obesity) directly affects inflammation, which in turn negatively affects muscle strength proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity.

12 overall reduction in muscle size and quality the number and size of skeletal muscle fibers decreases both with aging and obesity skeletal muscle protein synthesis decreases concurrent with muscle mitochondrial function (Marcell TJ, 2003). obesity exacerbates muscle fiber loss over the lifespan by reducing the muscle satellite cell DNA content and cell turnover (Peterson JM et al., 2008) fat infiltrates muscle tissue to create a marbling effect (Zamboni M et al, 2008). muscle power and strength decline (dynapenia) functional limitations and mobility disability Puthoff ML et al: 2007

13 the downward trend in muscle mass with aging seen in the context of the high degree of variability between individuals

14

15 Definizione di obesità sarcopenica Conseguenze cliniche

16

17 Frailty was originally characterized by Fried et al. (2001) as a condition that consists of at least three of five phenotypic criteria: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. The low proportion of muscle mass relative to the high proportion of fat mass can create frailty in the obese adult (Jarosz PA et al, 2009).

18 In post-menopausal women SO was associated to reduced cardio-pulmonary fitness (peak VO 2 and ventilatory threshold) (Oliveira R et al, 2011) higher risk of frailty and poorer quality of life (Janssen I et al, 2004; Villareal DT et al 2004), longer hospitalization (Kyle UG et al, 2005) and greater mortality rates (Honda H et al, 2007; Prado CM et al, 2008)

19

20

21 Clinical param. QoL obesity & Non sarcop Pre sarcop Sarcop Severe sarcop n M (n=30) F (n=48) Age (years) 57.8± ± ± ±8.7 < 65 yrs (%) ,3 42,1 Charlson Comorb Index 2.6± ± ± ±2.3 CRP- HS (mg/dl) 6.6± ± ± ±3.8 SF-36 PHI 31.7± ± ± ±12.2 Total score 32.7± ± ± ±13.0 p * p <0.05 between all four groups; p<0.05 between non sarcopenia and severe sarcopenia groups

22 Definizione di obesità sarcopenica Conseguenze cliniche Conseguenze funzionali

23

24

25

26 Ultrasound studies have demonstrated the importance in tendon changes in altering muscle power with aging. With aging there is a decrease in tendon stiffness which, coupled with the shortening of muscle fascicles, results in smaller pennation angles and a decrease in specific force (i.e., fascicle force/physiological crosssectional area). Aging is associated with a greater decline in lower body than upper body and extensor compared with flexor strength.

27 Multiple comorbidities (such as chronic obstructive pulmonary disease, vascular disease, fibromyalgia, gout and anxiety/depression) that commonly exist with either obesity or old age may generate exercise-induced pain and discomfort.

28 pressure increase in different foot areas of obese and particularly in sarcopenic obese higher loading during the stance phase comparing with non-sarcopenic non-obese discomfort and pain in the foot. limitation of basic daily activity tasks (e.g. walking)

29

30 Age-dependent adoption of a sedentary lifestyle may contribute to added fat accumulation, muscle atrophy, strain on muscles and joints. Adipose tissue which has infiltrated skeletal muscle mass is significantly associated with insulin resistance and systemic inflammation (Chevalier S et al: Am J Clin Nutr 2005 and J Gerontol A Biol Sci Med Sci 2006; Visser M et al: J Am Geriatr Soc 2002; Goodpaster BH et al: Am J Clin Nutr 2000)

31 Physical restrictions in obese subjects may be due to musculoskeletal pain due to osteoarthritis induced inflammation (Lamb et al, 2000; Grotle et al, 2008; Weaver et al, 2009) impaired functional tests of knee or back flexibility or strength but obese individuals demonstrate higher levels of kinesiophobia (fear of movement due to pain) compared with non-obese individuals presence of somatization and catastrophic thinking patterns (focus on the pain and negative aspects of pain hypervigilance to pain & anticipation of pain anxiety and somatic arousal with exercise and other physical activities) physical inactivity (Roelofs et al, 2004; Smits et al, 2010)

32 The term dynapenia has recently been coined to define the loss of strength associated with aging. Because obesity and dynapenia are each associated with physical function, it would be rational to hypothesize that older individuals with both a high fat mass and a low muscle strength (dynapenic-obese) would have greater impairments in their physical function than older individuals with obesity alone or dynapenia alone.

33

34

35

36 FM, HG strength and CRP, together with various chronic (joint diseases and diabetes mellitus in particular) significantly interact on walking limitation

37 OR for 2 self reported physical disabilities IADL Obesity: 1.34 M; 2.15 F Sarcopenia: 3.78 M; 2.96 F SO: 8.72 M; F Kaplan-Meier survival curve for time to drop in IADL by body composition type. Adjusted for age at baseline. NS, NO: nonsarcopenic, nonobese; S, NO: sarcopenic, nonobese; NS, O: nonsarcopenic, obese; S, O: sarcopenic, obese.

38 obesity & Non sarcop Pre sarcop Sarcop Severe sarcop p Anthrop. BMI (kg/m 2 ) 46.8± ± ± ±6.5 NS FM (%) 45.3± ± ± ±4.5 NS Function FFM (kg) 69.9± ± ± ±7.7 * FFMI 25.4±4 20.6±2 19.6±3 20,9±2 * FFMreal/FFMideal 0.99± ± ± ±0.04 * HGST (kg) 25.7± ± ± ±6.4 * 6MWT (m) 266± ± ±78 150±78 * 6MWT/pred-6MWT 0.76± ± ± ±0.28 * TSD-OC 56.2± ± ± ±8.7 * SPPB 8.5± ± ± ±1.8 * * p <0.05 between all four groups; p<0.05 between non sarcopenia and severe sarcopenia groups

39 Definizione di obesità sarcopenica Conseguenze cliniche Conseguenze funzionali Conclusioni

40

41 Both obesity and aging [characterized by a relative decline in muscle mass and strength (Baumgartner et al., 2004) concurrent with elevations in fat mass (Schultz et al., 2002)] can independently contribute to muscle inadequacy and deterioration of mobility The combination of the two likely exacerbates negative physiological changes in the musculoskeletal system and shapes However SO is not only characteristic of the geriatric age.

42 Obesity and sarcopenia can independently contribute to clinical and functional deterioration. But when they are combined the effect is more evident.

43 E N O I Z I R T U N E n L i A S I E C I L I F I F T R A X d e A C I N CLI Macchi M41 (1930)