Sarcopenic Obesity: Visceral Fat vs.
Skeletal Muscle Syndrome
Seok Won Park, MD, PhD, DrPH
Department of Internal Medicine
Concept of Sarcopenic Obesity (SO)
+
Problems of Misclassification (1)
Obesity: defined as excessive body fat mass
Excess fat mass
Excess non-fat
mass
Obesity
BMI > cut-point
True obesity
Non-obesity
BMI < cut-point
False (-): MONW
False (+): MHO
True non-obesity
Problems of Misclassification (2)
Metabolically unhealthy obesity: defined as obesity
causing metabolic derangements and CV complications
Metabolic
abnormality (+)
& CV risks
Metabolic
abnormality (-)
& CV risks
Obesity (+)
Obesity (-)
Truly unhealthy
; Tx. Needed
False (-): MONW
; Tx. Needed
False (+) MHO
; Tx. ?
True non-obesity
; No Tx.
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
Sarcopenia
Sarcopenic obesity
Synonyms of Sarcopenic Obesity
마른 비만
근육감소형 비만
올챙이형 인간, 거미형 인간
Metabolic Obese Normal Weight (MONW)?
Obesity/muscle impairment syndrome
Visceral fat vs. skeletal muscle syndrome
How to define Sarcopenic Obesity (SO)
Sarcopenia
aLM/ht2
BMI
Skeletal muscle index:
ASM/Wt (SMI, %)
Total body fat (%)
Waist circumference
Visceral fat area (VFA)
Cut-points ?
Obesity
< -1 SD
< -2 SD
Lower quintile
Problems in working definition of SO
Percent fat or fat/lean ratio, defines all obese as sarcopenic.
aLM/ht2 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/ht2 method
Fat & height method
(Newman et al., 2003)
Definition & Prevalence of SO
Chaos! (due to lack of standardization)
Sarcopenia
Obesity
Prevalence (%)
(F/M)
Baumgartner,
2000
ASM/ht2, < -2 SD total body fat %,
> Median
KSOS (0.8, 1.3)
Zoico, 2004
ASM/ht2,
2 lower quintile
total body fat %,
2 higher quintile
KSOS (16.5, 20.3)
Janssen modifed
by Kim, 2009
SMI, < -2 SD
total body fat %,
2 higher quintile
KSOS (12.5, 5.1)
Lim, 2010
ASM/ht2, < -1 SD VFA > 100 cm2
Lim, 2010
ASM/Wt , <-1 SD
VFA > 100 cm2
KLoSHA (48.1, 35.1)
Kim, 2013
SMI, <-1 SD
VFA > 100 cm2
KSOS (24.9, 17.8)
KLoSHA (5.7, 16.7)
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
Sarcopenic obesity – The fat impairs function
Overweight and obesity are risk factors for
disability independent of lean mass. (Visser M. et al.
JG:MS; 60:324-333, 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; 81:903-910,
2005)
Lean mass is not strongly related to function
once strength and IMF are considered. (Visser M. et al.
JAGS; 50:897-904, 2002)
Sarcopenic Obesity :
The War between Skeletal Muscle vs. Fat
win
defeat
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
Lifetime Trajectory of Body Weight and
Body Composition
일생동안 체중의 변화 (남자)
Kg
Kg
90
Weight
80
70
60
50
Lean mass
40
30
Fat mass
20
10
0
1
6
11 16 21 26 31 36 41 46 51 56 61 66 71 76 81
Age Age
(yr)
Loss of lean mass and gain in fat mass
Tradeoff going on regardless of weight trajectory
Proportional Changes in Lean and Fat
Compartments with Weight Loss vs. Gain
Women
25
25
20
20
15
17.9
10
5
1.98
0
-5.82
-5
-10
Loss
-10.6
Gain
Fat
Lean
% c h a n g e s in b o d y c o m p o s it io n
% c h a n g e s in b o d y c o m p o s itio n
Men
15
10
13.7
5
Fat
2.96
0
-5.02
-5
-10
-15
-15
-20
-20
Loss
-12.7
Gain
Lean
Weight and Body Composition
Age-related patterns of change
Weight Loss
Lean
Weight Stable
Lean
Weight Gain
Lean
Fat
Fat
Fat
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
Muscle fat impairs Strength
Men
Women
Intramuscular
fat
Specific force (Nm뷵m-2)
1.3
1.2
1.1
1.0
0.9
0.8
0.7
< 30.9
31.0-35.5 35.6-40. > 40.4
Muscle Attenuation (HU)
Goodpaster, BH J App Phys, 2001
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
Women
100
Five-Year Change (%)
Five-Year Change (%)
100
80
60
40
20
0
80
60
40
20
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.
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
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
The Concept of Sarcopenia
Causes
Loss of muscle mass
muscle quality ↓
(strength / unit mass)
Aging
Other risk factors ?
Loss of Strength
Outcomes
Functional limitations
Falls
Frailty
Mortality
Disability and
Loss of independence
Fractures
SW Park, 02/17/04
Current Concepts
Alternative Hypothesis
Nutritional, Hormonal, Metabolic, Immunologic Factors
Fat infiltration
Muscle function
Muscle mass
Strength
Weakness
Decreased activity
and immobility
Secondary atrophy
Disability, Morbidity, Mortality
Muscle mass
SW Park, 02/17/04
Visceral Fat vs Skeletal Muscle Syndrome
KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995
내장지방/ 골격근 증후군
Visceral Fat vs Skeletal Muscle Syndrome
대한내분비학회지 14(1) 1-13, 1999
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<0.001
2.35
P<0.001 2.35
2.5
2.02
2.02
1.96
1.88
1.90
1.73
1.5
SMI<41
fat mass>median
SMI>41
fat mass<median
Choi et al, Huh Diabetes Clinic, EASD 2009
Carotid maximal IMT and Insulin Resistance
Right CCA
Left CCA
1
1
0.95
0.95
0.9
0.9
0.85
0.85
0.8
0.8
0.75
0.75
0
0.7
1s t
2nd
3rd
4th
0
0.7
1s t
2nd
3rd
Kitt Quartile
Kitt Quartile
P <0.001
P <0.001
Park et al, Atherosclerosis 205:309-313, 2009
4th
Kim et al, Inter J Obe 33:131-135, 2009
Kim et al, Inter J Obe 34:105-110, 2010
Lim et al, Clin Endocrinol 73:588-594, 2010
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: 285-291, 2011
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 78:525-532, 2013
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
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
Visceral Fat vs Skeletal Muscle Syndrome
Cardiovascular Diseases
대한내분비학회지 14(1) 1-13, 1999
Discussion Points
Sarcopenia가 Obesity를 유발하는 기전?
Sarcopenia (low muscle mass and strength) as a risk
factor for obesity
Obesity가 sarcopenia를 유발하는 기전?
How to intervene sarcopenia-obesity link?
Discussion Point (1)
Sarcopenia가 Obesity를 유발하는 기전?
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.
Discussion Point (2)
Obesity가 sarcopenia를 유발하는 기전?
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.
Vicious cycle of obesity and sarcopenic obesity
Clin Geriatr Med 27:401-421, 2011
Discussion Point (3)
How to intervene sarcopenia-obesity link?
Lesson from Dr. Huh
당뇨병은 뱃살 (복부비만)과 다리 근육의
싸움이다.
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
Clin Geriatr Med 27:401-421, 2011
What is the matter?
Increased fatness or decreased muscle mass?
Summary
in the meantime
KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995
Age-Related Changes
in Body Composition
Loss of muscle mass
Increase proportion of body fat across life span,
age 18-85 (Novak, 1972)
18 to 36% in men
33 to 44% in women
Shift to more central fat distribution
About 1% per year in older adults
Visceral fat
intermuscular fat, intramyocellular fat
“ectopic” organ fat
Reduced bone mass
Lifetime Trajectory of Weight
(남자에서 가상적인 모델)
일생동안 체중의 변화 (남자)
Kg
90
80
70
60
50
40
30
20
10
0
1
6
11 16 21 26 31 36 41 46 51 56 61 66 71 76 81
Age
Lifetime Trajectory of Body Weight and
Body Composition
일생동안 체중의 변화 (남자)
Kg
90
Weight
80
70
60
Muscle mass
50
40
30
Fat mass
20
10
0
1
6
11 16 21 26 31 36 41 46 51 56 61 66 71 76 81
Age
Loss of lean mass and gain in fat mass
Tradeoff going on regardless of weight trajectory
Proportional Changes in Lean and Fat
Compartments with Weight Loss vs. Gain
Women
25
25
20
20
15
17.9
10
5
1.98
0
-5.82
-5
-10
Loss
-10.6
Gain
Fat
Lean
% c h a n g e s in b o d y c o m p o s it io n
% c h a n g e s in b o d y c o m p o s itio n
Men
15
10
13.7
5
Fat
2.96
0
-5.02
-5
-10
-15
-15
-20
-20
Loss
-12.7
Gain
Lean
Weight and Body Composition
Age-related patterns of change
Weight Loss
Lean
Weight Stable
Lean
Weight Gain
Lean
Fat
Fat
Fat
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.
Place of Sarcopenia in the Cycle of Frailty
Experimental Gerontology 43 (2008) 674-678
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
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
골감소증과 다른 점
1. 질량의 감소만을 의미하지 않는다.
2. 노화에 따른 근육 감소의 과정..
3. 이차적 원인을 배제하면서 동시에
근육병도 제외한다.
Sarcopenia
Age related loss of muscle mass
“Sarco” = Muscle, “-penia” = reduced
Low muscle mass & BeyondL
최근의 경향은 근육의 양적 감소에
국한하지 않고 근력의 저하를
포함한 개념으로 사용되고 있다.
Challenges in defining sarcopenia
근육량 측정 방법의 다양성
지표로 절대 근육량 사용시의 문제점
(body size 차이 감안해야 할 필요성)
비교 대상 (reference population)
근육량의 차이가 결과(outcome)의 차이를
충분히 설명하지 못한다.
양보다 질의 문제 ??
Measurements of skeletal muscle mass
Anthropometric approaches
Volume displacement methods
Bioimpedance techniques (BIA)
DEXA
Multiscan CT
MRI
Whole body DEXA
Sarcopenia: Definition and Epidemiology
%
Baumgartner RN, 1998
Lean Mass Index
(appendicular lean mass in kg
/ height in m2) < -2SD of
young adult mean
Men
Women
Prevalence (%) of Sarcopenia in New Maxico
Elder Health Survey, by age, sex, and ethnicity
Am J Epidemiol 147:755-763, 1998
Prevalence of sarcopenia varies by
operational Definitions
Author (year)
Definition
Baumgartner,
1998
aLM / ht2 < 2
Imputation
sd below young using
anthropometry
/grip strength
M W
70-74 19.8 33.3
75-80 26.7 35.9
Melton III, 2000
aLM / ht2 < 2
DXA
sd below young
M W
70-79 16.0 11.8
80+
34.0 4.0
Janssen, 2002
Muscle mass/
BIA
total mass < 2
sd below young
Tanko, 2002
Technique
aLM / ht2 < 2
DXA
sd below young
Prevalence (%)
70-79
80+
60-69
70+
M
7
7
W
11
11
W
9.4
12.3
Operational Definitions of
Sarcopenia II
Author (year)
Definition
Technique Prevalence (%)
Castillo, 2003
FFM < 2 sd
below young
BIA
Muscle mass /
ht2 < 2 sd
below young
BIA
Janssen, 2006
Newman, 2003
Lowest quintile DXA
of residual aLM
after regressing
fat mass on
aLM
55-98
M
W
6.2 5.9
65 +
M
W
17.1 10.7
70-79
M
W
20 20
Problems in Baumgartner’s Definition
In Health ABC study
aLM/ht2 highly correlated with BMI
r = 0.76 (men), 0.85 (women)
Identified thin Health ABC
participants as sarcopenic
aLM/ht2 method
Fat & height method
(Newman et al., 2003)
Newman’s method – fat mass and height adjusted
Fat mass and height relative to appendicular lean mass (aLM)
Prevalence Odds Ratio* (95% CI) of having a
Low SPPB Score in the Health ABC study:
Two Definitions of Sarcopenia
aLM/ht2
Men
1.5
(1.1, 2.1)
Women
0.9
(0.7, 1.2)
Residual
Method
1.8
1.9
(1.3, 2.5)
(1.4, 2.5)
*adjusted for age, race, smoking, drinking, co-morbidity, physical activity, and BMI
(aLM/ht2 only)
Newman et al, J Am Geriatrics Soc 2003;51:1602-9.
RESULTS
Incident persistent lower extremity limitation by the fat &
height adjusted and aLM/ht2 methods.
Normal
Sarcopenic
n
9.7
289
10.6
0.91 (0.73-1.15)
--
1229
15.0
314
17.2
1.34 (1.11-1.61)
--
Men
1142
10.0
291
9.4
0.76 (0.60-0.96) 0.84 (0.66-1.08)
Women
1231
17.1
312
9.8
0.75 (0.60-0.93) 1.04 (0.82-1.31)
Fat & Height Method
Men
1144
Women
Events/100 Adjusted HR*
Person-yrs
(95% CI)
Adjusted HR†
(95% CI)
Events/100
Person-yrs
n
aLM/ht2 Method
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/ht2 method, HRs additionally adjusted for total body fat mass.
Odds of Prevalent ADL, IADL Difficulties in
167 Women, 67-87 years old
aLM/ht2*
BMI
SMI
(Muscle/Total
Mass)**
20-24.9
1.0
normal
1.0
1.0
25-29.9
1.01
1-2 sd below
young
0.54
1.57
> 30
4.56§
< 2 sd below
young
0.98
3.86§
Adjusted for age, heart disease, hypertension, diabetes, arthritis.
*Using Cut-points from Baumgartner et al, 1998.
**Using Cut-points from Janssen et a, 2002
§P < 0.05
Zoico E et al. Int J Obesity 2004;28:234-41
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
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
Prerequisite for defining sarcopenia
Standardization of measurements
Reference (healthy population) data
Simple and easy in clinical setting
Should predict outcomes !!!
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;412-423
Categories of Sarcopenia
Stages of Sarcopenia
Measurements
Algorithm for sarcopenia case finding
Mean IMT according to WC & VFT
†
*
Mean IMT (mm)
0.8
0.6
0.4
0.2
0
≥ 47.6
< 47.6
VFT (mm)
≥ 90
< 90
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.
Case (M, 48)
IFG, r/o T2DM, FHx: Father – DM
Ht 170cm, Wt 65kg, BMI 22.5, WC 90cm
1 년전 개원하면서 운동은 거의 못하고 잦은 음주
2011. 3. FBS 116, A1c 6.9%, Lipid 232/279/42/121
식이 조절과 함께 하루 8km 걷기 운동, 주 5일
2011. 5. FBS 111, A1c 6.4%, Lipid 212/114/48/110
2011. 7. FBS 108, A1c 5.8%, Lipid 190/115/56/98
체중은 1kg 밖에 안 빠졌는데 허리 둘레가 많이 줄었다.
Currently used Definitions of SO
Visceral Fat vs Skeletal Muscle Syndrome
KB Huh et al. 8th Japan-Korea symposium on diabetes mellitus, 1995
대한내분비학회지 14(1) 1-13, 1999