Sarcopenic Obesity: Visceral Fat vs. Skeletal Muscle Syndrome. Seok Won Park, MD, PhD, DrPH Department of Internal Medicine

Transcription

1 Sarcopenic Obesity: Visceral Fat vs. Skeletal Muscle Syndrome Seok Won Park, MD, PhD, DrPH Department of Internal Medicine

2 Concept of Sarcopenic Obesity (SO) +

3 Problems of Misclassification (1) Obesity: defined as excessive body fat mass Obesity Non-obesity BMI > cut-point BMI < cut-point Excess fat mass True obesity False (-): MONW Excess non-fat mass False (+): MHO True non-obesity

4 Problems of Misclassification (2) Metabolically unhealthy obesity: defined as obesity causing metabolic derangements and CV complications Obesity (+) Obesity (-) Metabolic abnormality (+) & CV risks Metabolic abnormality (-) & CV risks Truly unhealthy ; Tx. Needed False (+) MHO ; Tx.? False (-): MONW ; Tx. Needed True non-obesity ; No Tx.

5 Problems of Misclassification (3) Body weight and/or BMI is a composite of both fat and lean mass. What matters is a body composition and its distribution (proportional issue). Recently, importance of skeletal muscle mass / function is highlighted. Obesity Non-obese Normal muscle mass Non-sarcopenic obesity Non-sarcopenic non-obese Low muscle mass Sarcopenic obesity Sarcopenia

6 Synonyms of Sarcopenic Obesity 마른비만 근육감소형비만 올챙이형인간, 거미형인간 Metabolic Obese Normal Weight (MONW)? Obesity/muscle impairment syndrome Visceral fat vs. skeletal muscle syndrome

7 How to define Sarcopenic Obesity (SO) Sarcopenia alm/ht 2 Skeletal muscle index: ASM/Wt (SMI, %) Cut-points? < -1 SD < -2 SD Lower quintile Obesity BMI Total body fat (%) Waist circumference Visceral fat area (VFA)

8 Problems in working definition of SO Percent fat or fat/lean ratio, defines all obese as sarcopenic. alm/ht 2 is highly correlated with BMI (r, 0.76~0.85), mostly lean are sarcopenic SMI (ASM/Wt), just opposite of percent fat (fat/wt) Fat and height adjusted lean mass 11% of men and 15% of women were sarcopenic- obese in Health ABC. This definition was most strongly related to function in both men and women alm/ht 2 method Fat & height method (Newman et al., 2003)

9 Definition & Prevalence of SO Chaos! (due to lack of standardization) Baumgartner, 2000 Zoico, 2004 ASM/ht 2, 2 lower quintile Janssen modifed by Kim, 2009 Sarcopenia Obesity Prevalence (%) (F/M) ASM/ht 2, < -2 SD total body fat %, > Median total body fat %, 2 higher quintile SMI, < -2 SD total body fat %, 2 higher quintile KSOS (0.8, 1.3) KSOS (16.5, 20.3) KSOS (12.5, 5.1) Lim, 2010 ASM/ht 2, < -1 SD VFA > 100 cm 2 KLoSHA (5.7, 16.7) Lim, 2010 ASM/Wt, <-1 SD VFA > 100 cm 2 KLoSHA (48.1, 35.1) Kim, 2013 SMI, <-1 SD VFA > 100 cm 2 KSOS (24.9, 17.8)

10 Sarcopenic obesity What is it? Sarcopenic obesity Obesity WITH Lower muscle mass than expected AND Age-related body composition changes Loss of lean mass and Fat infiltration into muscle. Is also used to refer to muscle weakness and poor metabolic profile in obese elderly

11 Sarcopenic obesity The fat impairs function Overweight and obesity are risk factors for disability independent of lean mass. (Visser M. et al. JG:MS; 60: , 2005) Direct and indirect effects: Fat has a direct impact on poor function Indirect effect through weight related health conditions (esp. diabetes and arthritis) Higher total fat is highly correlated with greater muscle fat infiltration. (Gallagher D, Am J Clin Nutr; 81: , 2005) Lean mass is not strongly related to function once strength and IMF are considered. (Visser M. et al. JAGS; 50: , 2002)

12 Sarcopenic Obesity : The War between Skeletal Muscle vs. Fat win defeat

13 Invasion of fat with aging Accumulation of adipose tissue in the abdominal cavity (visceral fat) Infiltration of adipose tissue into the muscle Indirect attack through various adipo-cytokines (TNF-α, IL-6, ), which induce inflammations Ectopic fat deposition (liver, pancreas, heart, etc) which impairs organ function

14 Lifetime Trajectory of Body Weight and Body Composition Kg Kg 일생동안체중의변화 ( 남자 ) Weight Lean mass Fat mass Age Age (yr)

15 Loss of lean mass and gain in fat mass Tradeoff going on regardless of weight trajectory

16 Proportional Changes in Lean and Fat Compartments with Weight Loss vs. Gain Men Women % c h a n g e s in b o d y c o m p o s itio n Loss Gain Fat Lean % c h a n g e s in b o d y c o m p o s it io n Loss Gain Fat Lean

17 Weight and Body Composition Age-related patterns of change Weight Loss Weight Stable Weight Gain Lean Lean Lean Fat Fat Fat

18 Skeletal Muscle fat Less More Most CT Scans of the mid thigh from actual Health ABC participants showing muscle area, subcutaneous fat and intermuscular fat (highlighted in pink) variability in thighs of similar cross-sectional area

19 Muscle fat impairs Strength Intramuscular fat Specific force (Nm 뷵 m-2) Men Women 0.7 < > 40.4 Muscle Attenuation (HU) Goodpaster, BH J App Phys, 2001

20 100 Muscle fat infiltration increases with age, even with weight loss Five-Year % Change in Thigh Intermuscular Fat in Men and Women by Weight Change Group Men 100 Women Five-Year Change (%) Five-Year Change (%) Weight Gainers Weight Stable Weight Losers 0 Weight Gainers Weight Stable Weight Losers Goodpaster B, et al. Sarcopenia, Muscle Fat Accumulation and the Loss of Strength with Age. The Gerontologist. 2006;46(S1):336.

21 Discordance of Muscle mass & strength Why? (changes in muscle composition and quality) QMA: Quadriceps muscle area MT: Muscle torque SF: Subcutaneous fat IMF: Intermuscular fat

22 Rethinking sarcopenic obesity Lean and fat move together Stresses need to consider muscle and fat together Coupling of body composition compartments (Forbes GB. 1999) Key features and distinct targets are the fat, muscle strength and fat in muscle Although sarcopenic obesity captures an important concept Need to refocus away from sarcopenia and on the fat and muscle quality

23 The Concept of Sarcopenia Causes Loss of muscle mass Aging Other risk factors? muscle quality (strength / unit mass) Loss of Strength Outcomes Disability and Functional limitations Loss of independence Falls Fractures Frailty Mortality SW Park, 02/17/04

24 Current Concepts Alternative Hypothesis Nutritional, Hormonal, Metabolic, Immunologic Factors Fat infiltration Muscle mass Muscle function Strength Weakness Disability, Morbidity, Mortality Decreased activity and immobility Secondary atrophy Muscle mass SW Park, 02/17/04

25 Visceral Fat vs Skeletal Muscle Syndrome KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995 내장지방 / 골격근증후군

26 Visceral Fat vs Skeletal Muscle Syndrome 대한내분비학회지 14(1) 1-13, 1999

27 Low Relative Skeletal Muscle Mass is Independently Associated with Insulin Resistance in Patients with Type 2 Diabetes Insulin sensitivity (kitt) of subjects according to skeletal muscle index (SMI) and fat mass (A) men P<0.001 (B) women P< P< SMI<41 SMI>41 fat mass>median fat mass<median Choi et al, Huh Diabetes Clinic, EASD 2009

28 Carotid maximal IMT and Insulin Resistance 1 Left CCA 1 Right CCA st 2nd 3rd 4th Kitt Quartile s t 2nd 3rd 4th Kitt Quartile P <0.001 P <0.001 Park et al, Atherosclerosis 205: , 2009

29 Kim et al, Inter J Obe 33: , 2009

30 Kim et al, Inter J Obe 34: , 2010

31 Lim et al, Clin Endocrinol 73: , 2010

32 Skeletal muscle mass to visceral fat area ratio is associated with metabolic syndrome and arterial stiffness: The Korean Sarcopenic Obesity Study (KSOS) Fig. 1 Relationship between the ratio of the appendicular skeletal muscle mass-to-visceral fat area (MFR) and mean brachial-ankle pulse wave velocity (PWV). Kim TN, et al, DRCP 93: , 2011

33 Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: KSOS HOMA-IR hs-crp 25(OH)D Kim TN, et al, Clin Endocrinol 78: , 2013

34 Ratio of Waist-to-Calf Circumference and Carotid Atherosclerosis in Korean Patients with Type 2 Diabetes Kim SK, et al. Diabetes Care 34(9): 2067-, 2011

35 Number of cardiovascular disease events per 10,000 person-years according to abdominal obesity and sarcopenia classified using either obesity X muscle mass (Panel A) or obesity X muscle strength (Panel B) NL Sarcopenia Obese SO NL Sarcopenia Obese SO

36 Visceral Fat vs Skeletal Muscle Syndrome Cardiovascular Diseases 대한내분비학회지 14(1) 1-13, 1999

37 Discussion Points Sarcopenia 가 Obesity 를유발하는기전? Sarcopenia (low muscle mass and strength) as a risk factor for obesity Obesity 가 sarcopenia 를유발하는기전? How to intervene sarcopenia-obesity link?

38 Discussion Point (1) Sarcopenia 가 Obesity 를유발하는기전? Sarcopenia (low muscle mass and strength) as a risk factor for obesity Low muscle mass = reduced BMR Weakness = reduced PA 1+2= decline in T.E.E.

39 Discussion Point (2) Obesity 가 sarcopenia 를유발하는기전? IR impaired muscle protein turnover Adipokines induce Low grade inflammation High FFA suppression of GH-IGF axis Low testosterone activity Reduced PA = loss of muscle mass & fc.

40 Vicious cycle of obesity and sarcopenic obesity Clin Geriatr Med 27: , 2011

41 Discussion Point (3) How to intervene sarcopenia-obesity link?

42 Lesson from Dr. Huh 당뇨병은뱃살 ( 복부비만 ) 과다리근육의 싸움이다.

43 Acknowledgement YW Cho, SK Kim, CHA University KB Huh, My life-long mentor. Anne B. Newman, Bret H. Goodpaster, University of Pittsburgh, Tamara Harris, NIA, NIH IAGG Seoul Symposium; SO, The link between fat and muscle, COEX, 8:00~9:30, 26, June, 2013

44 Clin Geriatr Med 27: , 2011

45 What is the matter? Increased fatness or decreased muscle mass?

46

47 Summary in the meantime

48 KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995

49 Age-Related Changes in Body Composition Loss of muscle mass About 1% per year in older adults Increase proportion of body fat across life span, age (Novak, 1972) 18 to 36% in men 33 to 44% in women Shift to more central fat distribution Visceral fat intermuscular fat, intramyocellular fat ectopic organ fat Reduced bone mass

50 Lifetime Trajectory of Weight ( 남자에서가상적인모델 ) Kg 90 일생동안체중의변화 ( 남자 ) Age

51 Lifetime Trajectory of Body Weight and Body Composition Kg 일생동안체중의변화 ( 남자 ) Weight Muscle mass Fat mass Age

52 Loss of lean mass and gain in fat mass Tradeoff going on regardless of weight trajectory

53 Proportional Changes in Lean and Fat Compartments with Weight Loss vs. Gain Men Women % c h a n g e s in b o d y c o m p o s itio n Loss Gain Fat Lean % c h a n g e s in b o d y c o m p o s it io n Loss Gain Fat Lean

54 Weight and Body Composition Age-related patterns of change Weight Loss Weight Stable Weight Gain Lean Lean Lean Fat Fat Fat

55

56 Sarcopenia - Hypotheses Muscle mass is a major determinant of function and mortality (particularly in older adults). Strategies to preserve lean mass may improve functional independence, while loss of lean mass would likely accelerate loss of function.

57 Place of Sarcopenia in the Cycle of Frailty

58 Experimental Gerontology 43 (2008)

59 Consequences of sarcopenia Muscle weakness Functional impairments Disability Loss of independence Falls and fractures Mortality Others: pharmacokinetic change, decline in RMR, fat accumulation (obesity), insulin resistance, glucose intolerance and diabetes

60 What is sarcopenia? ( 근감소증, 골격근감소증 ) Muscle mass ( sarx is flesh) that is reduced in quantity ( penia is loss). Refers to the process of loss of muscle mass with aging (IH Rosenberg: AJCN 1989;50(suppl):1231-3, WJ Evans: J Nutr 1993;123:465-8) Is distinguished from: Cachexia Wasting Muscle Disease 골감소증과다른점 1. 질량의감소만을의미하지않는다. 2. 노화에따른근육감소의과정.. 3. 이차적원인을배제하면서동시에근육병도제외한다.

61 Sarcopenia Age related loss of muscle mass Sarco = Muscle, -penia = reduced Low muscle mass & Beyond 최근의경향은근육의양적감소에 국한하지않고근력의저하를 포함한개념으로사용되고있다.

62 Challenges in defining sarcopenia 근육량측정방법의다양성 지표로절대근육량사용시의문제점 (body size 차이감안해야할필요성 ) 비교대상 (reference population) 근육량의차이가결과 (outcome) 의차이를충분히설명하지못한다. 양보다질의문제??

63 Measurements of skeletal muscle mass Anthropometric approaches Volume displacement methods Bioimpedance techniques (BIA) DEXA Multiscan CT MRI

64 Whole body DEXA

65 Sarcopenia: Definition and Epidemiology Baumgartner RN, 1998 % Lean Mass Index (appendicular lean mass in kg / height in m 2 ) < -2SD of young adult mean Men Women Prevalence (%) of Sarcopenia in New Maxico Elder Health Survey, by age, sex, and ethnicity Am J Epidemiol 147: , 1998

66 Prevalence of sarcopenia varies by operational Definitions Author (year) Definition Technique Prevalence (%) Baumgartner, 1998 alm / ht 2 < 2 sd below young Imputation using anthropometry /grip strength M W Melton III, 2000 alm / ht 2 < 2 sd below young DXA M W Janssen, 2002 Muscle mass/ total mass < 2 sd below young BIA M W Tanko, 2002 alm / ht 2 < 2 sd below young DXA W

67 Operational Definitions of Sarcopenia II Author (year) Definition Technique Prevalence (%) Castillo, 2003 FFM < 2 sd below young Janssen, 2006 Muscle mass / ht 2 < 2 sd below young BIA BIA M W M W Newman, 2003 Lowest quintile of residual alm after regressing fat mass on alm DXA M W

68 Problems in Baumgartner s Definition In Health ABC study alm/ht 2 highly correlated with BMI r = 0.76 (men), 0.85 (women) Identified thin Health ABC participants as sarcopenic (Newman et al., 2003) Newman s method fat mass and height adjusted alm/ht 2 method Fat & height method Fat mass and height relative to appendicular lean mass (alm)

69 Prevalence Odds Ratio* (95% CI) of having a Low SPPB Score in the Health ABC study: Two Definitions of Sarcopenia alm/ht 2 Residual Method Men 1.5 (1.1, 2.1) 1.8 (1.3, 2.5) Women 0.9 (0.7, 1.2) 1.9 (1.4, 2.5) *adjusted for age, race, smoking, drinking, co-morbidity, physical activity, and BMI (alm/ht 2 only) Newman et al, J Am Geriatrics Soc 2003;51:

70 RESULTS Incident persistent lower extremity limitation by the fat & height adjusted and alm/ht 2 methods. Normal Sarcopenic Fat & Height Method n Events/100 Person-yrs n Events/100 Person-yrs Adjusted HR* (95% CI) Adjusted HR (95% CI) Men ( ) -- Women ( ) -- alm/ht 2 Method Men ( ) 0.84 ( ) Women ( ) 1.04 ( ) Five years of follow-up. Mean follow-up time (FU) of 3.2 (SD = 0.8) years. *Adjusted for age, race, comorbidity, smoking, alcohol use, physical activity baseline lower extremity performance score, and interim hospitalization. When using the alm/ht 2 method, HRs additionally adjusted for total body fat mass.

71 Odds of Prevalent ADL, IADL Difficulties in 167 Women, years old BMI alm/ht 2* (Muscle/Total SMI Mass)** normal sd below young > < 2 sd below young Adjusted for age, heart disease, hypertension, diabetes, arthritis. *Using Cut-points from Baumgartner et al, **Using Cut-points from Janssen et a, 2002 P < 0.05 Zoico E et al. Int J Obesity 2004;28:234-41

72 Sarcopenia Mass vs. Strength Lean mass is not a good surrogate for strength or function Muscle mass per se is not as important as muscle function in predicting outcomes Strength is not a good surrogate for sarcopenia Much more work is needed to define the additional factors that contribute to strength loss and other aspects of muscle function change

73 Summary of Controversies Sarcopenia Definitions No consensus on best metric Controversy about whether it is appropriate to anchor definition to young controls cohort effects Validation criterion Disability? Mortality? Individual change may be best definition for tracking health

74 Prerequisite for defining sarcopenia Standardization of measurements Reference (healthy population) data Simple and easy in clinical setting Should predict outcomes!!!

75 Working definition (2010, EWGSOP) 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. Age & Aging 2010: 39;

76 Categories of Sarcopenia

77 Stages of Sarcopenia

78 Measurements

79 Algorithm for sarcopenia case finding

80

81 Mean IMT according to WC & VFT * 0.8 Mean IMT (mm) < < 47.6 VFT (mm) Waist (cm) p < 0.05, p < 0.01 compared to Waist < 90 cm & VFT < 47.6 mm Adjusted for age, systolic pressure, total cholesterol and HOMA-IR.

82

83 Case (M, 48) IFG, r/o T2DM, FHx: Father DM Ht 170cm, Wt 65kg, BMI 22.5, WC 90cm 1 년전개원하면서운동은거의못하고잦은음주 FBS 116, A1c 6.9%, Lipid 232/279/42/121 식이조절과함께하루 8km 걷기운동, 주 5일 FBS 111, A1c 6.4%, Lipid 212/114/48/ FBS 108, A1c 5.8%, Lipid 190/115/56/98 체중은 1kg 밖에안빠졌는데허리둘레가많이줄었다.

84 Currently used Definitions of SO

85 Visceral Fat vs Skeletal Muscle Syndrome KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995 대한내분비학회지 14(1) 1-13, 1999