Sarcopenic Obesity Prof Mauro Zamboni

Department of Medicine-Geriatric Division

University of Verona-Italy

4ST International Seminar on Preventive Geriatrics

Athens

April 1st-3rd 2011

Sarcopenic Obesity

R Roubenoff, 2004

Epidemicof Obesity

Prevalence of Obesity and Overweight for Adults Aged 20 Years or Older

Flegal, K. M. et al. 2010;303:235-241

BMI

underweight

normalweight

overweight

obesity

morbid obesity

< 18.5

18.5-25

25-30

> 30

>40

WHO, 1998

weight (kg)

height (m)2 BMI =

Obesity should be identified as the degree of fat storage associated with elevated health risk.

The practical definition of Obesity is based on BMI

Sarcopenic Obesity

Epidemicof Obesity

Aging of the

population

Age related body composition changes

Age related increase in body fat for normal males at constant body mass

index (BMI)

10

20

30

40

25 35 45 55 65 75

0

10

20

30

40

50

60

70

80

90

100

Body fat (%)

Body weight

(kg)

Age (years)

Prentice AM & Jebb SA, 2001

Age-related decreases in thigh muscle area, knee extensor strenght, and aerobic capacity

in 78 healthy persons

Nair KS, Am J Clin Nutr 2005

Normal Obese

SarcopenicSarcopeni

cObese

5.0

6.0

7.0

Rela

tive M

usc

le M

ass

(kg

/m2

)

20 30 40% Body Fat

Median

-2 S

D b

el o

wYou

ng a

dult

mean

Baumgartner, 2000

Body composition in healthy aging: the New Mexico Body composition in healthy aging: the New Mexico Elder Health Survey and the New Mexico Aging Elder Health Survey and the New Mexico Aging

Process StudyProcess Study

Definition of Sarcopenic Obesity

SarcopeniaMuscle mass/ height squared

less than -2SD below the young adult mean

Sarcopenic obesityMuscle mass/ height squared

less than -2SD below the young adult reference mean

with % Fat > 27 in men and 38 in women

or BMI > 30

Prevalences of obesity, sarcopenia and sarcopenic-Prevalences of obesity, sarcopenia and sarcopenic-obesity by age in the combined New Mexico Elder obesity by age in the combined New Mexico Elder

Health Survey and New Mexico Aging Process StudyHealth Survey and New Mexico Aging Process Study

0

10

20

30

40

50

60%

<70 y

70-74 y 75-79 y >80 y

Obese

Normal

SarcopenicSarcopenic-Obese

Baumgartner et al, 1998

Comparison of different sarcopenic obesity definitions and prevalences

Definition of sarcopenic obesity

N Mean age (SD) Prevalence*

New Mexico Aging Process Study

•Sarcopenia: skeletal muscle mass -2 SD below mean of young population or < 7.26 kg/m2 in men and < 5.45 kg/m2 in women. •Obesity: percentage body fat greater than median or > 27% in men and 38% in women.

831 60 and over M: 4.4%F: 3.0%

NHANES III •Sarcopenia: two lower quintiles of muscle mass (<9.12 kg/m2 in men and <6.53 kg/m2 in women) •Obesity: two highest quintiles of fat mass (>37.16% in men and > 40.01% in women).

M: 1391F: 1591

M: 76.3 (1.7†)F: 77.3 (2.2†)

M: 9.6%F: 7.4%

Zoico et al •Sarcopenia: two lower quintiles of muscle mass (<5.7 kg/m2) •Obesity: two highest quintiles of fat mass (>42.9%)

F: 167 71.7 (2.4) F: 12.4%

*Age and gender adjusted prevalence.

†Standard error Stenholm Curr Opin Clin Nutr Metab Care 2008

Quantity or Quality Quantity or Quality of fat free mass and fat of fat free mass and fat

mass ? mass ?

a potential problems with definition of Sarcopenic Obesity:

Loss of leg lean mass and muscle strength in older Results from the Health, Aging and

Body Composition Study

Goodpaster et al. J Gerontol Med Sci, 2006

Definition based on hand grip strength

(instead of muscle mass) and BMI in four

epidemiological studies gives a

prevalence of Sarcopenic Obesity

between 4-9%

With Sarcopenic Obesity increases in

Intermuscular Fat

and Intramuscular

fat: Low Density

Lean Tissue by CT

0

0,5

1

1,5

2

2,5

3

3,5

VAT IMAT VAT IMAT

<35

35-59

60+

kilog

ram

s

of

ad

ipose

Visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) increase

with age

Men Women

Gallagher et al., 2004

Body fat changes and ectopic fat deposition

in the elderly

Abdominal subcutaneous fat

Inter-intramuscular fat

Hepatic and pancreatic fat Abdominal

visceral AT

Epicardial fat, perivascular fat

Subcutaneous fatLower body

If loss of muscle mass or strength

Sarcopenic obesity

Muscle-Fat

a two-way cross-talk ?

What is the biological connection between

Sarcopenia and Obesity?

Nair KS, 2005

Does muscle loss cause fat gain ?

Adipose tissue

Pro-inflammatory cytokines

Pathways to sarcopenia ?

Does Fat gain cause Muscle loss?

Anti-inflammatory cytokines

Juge-Aubry CE et al, 2005

Man 79 years

BMI 35.21 Kg/m²

Obese sarcopenic subject Normal weight subject

80 years80 yearsBMI 26 Kg/m²BMI 26 Kg/m²

79 years79 yearsBMI 35.2 Kg/m²BMI 35.2 Kg/m²

Rossi et al. Obesity 2010 Mar 18

Association between intermuscular

adipose tissue area (IMAT), metabolic

variables, indices of sistemic and local

inflammation in 20 elderly men

Insulin HOMA Leptin hs-CRP

r 0.55 r 0.49

r 0.76

r 0.40

p<0.05

p<0.001

p<0.01

IL-6

r 0.11

IL-6 mRNA SAT

r 0.50

p<0.05

Zoico E, Zamboni M et al. 2009

Subcutaneous AT

Peritoneal AT

Peri Aortic AT

Epicardial AT

35 men aged 65.7±5 with coronary artery diseases or valve diseases35 men aged 65.7±5 with coronary artery diseases or valve diseases

SAT EAT

SAT

SAT

AOAT

EAT

EAT

AOAT

AOAT

*

*

Ad

ipon

ect

Ad

ipon

ect

ininM

CP

-1M

CP

-1

CD

-3C

D-3

*=p<0,05

**

**

Bambace et al. Cardiovascular Pathology 2010

A. B.

C. D.

Inflammatory cells and pericardial fat

macrophages

linphocytes

University of Verona 2010, to be submitted

University of Verona 2010, to be submitted

Human atrium stained with hematoxylin and eosin; Magnification. A. 10x; B. 20x; Scale bar: A. = 200μm; B.= 100μm

9 subjects of 35 (4 CAD; 5 nonCAD)

Age M ± SD 69,55 ± 7.50 years

BMI 27.33±1.98 kg/m2

University of Verona 2010, to be submitted

Staining: Perilipin + hematoxylin; Magnification: A.B. 10x ; C. 100x ; D. 40x

Scale bar: A. and B.= 200μm; C. = 20μm; D. = 50μm

Grp-75 marker of mithocondrial

stress

Grp-78 marker of

endoplasmatic reticolus stress

Grp-75 Grp-78University

of Verona and Brescia. Unpublished

Grp-75 Grp-78

subject 42

University of Verona and Brescia.

Unpublished

fibrosis

Miosteatosis plus MiofibrosisMiosteatosis plus Miofibrosisfor muscle quality?for muscle quality?

University of Verona Unpublished

miofibrosismiofibrosis

miosteatosismiosteatosis

Obesity acts synergistically with sarcopenia

to maximize the risk of physical

disability

Associations between purely sarcopenic, purely obese, or sarcopenic-obese subjects and self-reported difficulties

with physical function

Rolland Y, 2009

Incidence of Sarcopenia and Sarcopenic Incidence of Sarcopenia and Sarcopenic Obesity Obesity

(7 year follow-up)(7 year follow-up)

0

10

20

30

40

50

60

70

80

90

100

sarcopenic obese sarcopenic

%

19%

49%

Rossi A et al, 2008

Relative Risk of Pulmonary declineRelative Risk of Pulmonary declineby body composition changesby body composition changes(adjusted by sex and smoking)(adjusted by sex and smoking)

0

2

4

6

8

10

12

14

16

18

20

FFM decline FFM stable

SAD decline

SAD increas

* p<0.05

OR

*

*

Sarcopenic obeseOR=14

Rossi A et al, 2008

Differences in muscle density , muscle area ratio and fat area ratio, according frailty syndrome status

923 subjects, aged 65 years or older

The fat frail sarcopenic subject

Sarcopeniareduced muscle mass

and strenght

Obesitymainly

visceral obesity

Risk Falls

Fractures

PhysicalDisability

DiabetesHypertensionDyslipidemia

CVD

Insulin resistance

Zamboni et al, 2008

The concept of Sarcopenic Obesity

could help us understand the

complexity of the relation between

obesity, mortality and morbidity in

the elderly

Better knowledge of the biological

connection between sarcopenia and

obesity is needed

Better definition of sarcopenic

obesity is warranted