57 Congresso SIGG · 57° Congresso SIGG MiCo – Milano Convention Center 21/11/2012 - 24/11/2012...

57° Congresso SIGG

MiCo – Milano Convention Center

21/11/2012 - 24/11/2012

SIMPOSIO

“Gruppo di Lavoro Italiano sulla Sarcopenia”

TRATTAMENTO E NUTRIZIONE

Proposta di uno studio italiano sulla sarcopenia

Abete P, MD, PhD

Cattedra di Geriatria

Dipartimento di Medicina clinica, Scienze cardiovascolari ed immunologiche

Università di Napoli Federico II

LA SARCOPENIA NELL‟ANZIANO:

ALTERAZIONI BIOCHIMICO-MORFO-FUNZIONALI

E RISCHIO DI EVENTI AVVERSI

NAPOLI

FERRARA

MODENA

ROMA

FIRENZE

VERONA

Proposta di uno studio italiano

sulla “SARCOPENIA”

57° Congrsso

SIGG

SARCOPENIA

COPD

DIABETES

CHF

CHRONIC

RENAL

FAILURE

DEMENTIA

FALLS



57° Congrsso

SIGG

SARCOPENIA

DIABETES

Prevalence and Determinant Factors of

Sarcopenia in Patients With Type 2 Diabetes

Kim TN et al., Diabetes care 2010

MEN WOMEN



57° Congrsso

SIGG

SARCOPENIA

DEMENTIA

Reduced Lean Mass in Early Alzheimer Disease

and Its Association With Brain Atrophy

Burns JM et al., Arch Neurol. 2010



57° Congrsso

SIGG

SARCOPENIA

CHF

Relationship between chronic heart failure

severity and sarcopenia

Pu CT et al, J Appl Physiol 2001

uri

na

ry 3

-me

thylh

isti

din

e e

xc

reti

on

(mm

ol/g

cre

ati

nin

e)

NYHA



57° Congrsso

SIGG

SARCOPENIA

COPD

Sarcopenia and respiratory function in older

patients with COPD

Cesari M et al., Age & Ageing 2012

Beta

co

eff

icie

nt

Results from separate linear regression models predicting 6MWT

p=0.006 P<0.001



57° Congrsso

SIGG

SARCOPENIA

FALLS

No Injurious falls

Injurious fall

Kg

Injurious falls in the year following hip fracture A Prospective Study of Incidence and Risk Factors From the

Sarcopenia and Hip Fracture Study

Lloyd BD et al., J Gerontol 2009

P=0.01 P=0.03



57° Congrsso

SIGG

SARCOPENIA

CHRONIC

RENAL

FAILURE

Control

Renal transplantation

Hemodialysis

van den Hama EC et al., Ann Transplant 2005

Skeletal muscle strength and exercise capacity

between renal transplant and hemodialysis pts

nM

/kg

*

mL

/min

*

*p<0.05 vs renal transplantatione and hemodialysis



57° Congrsso

SIGG

OBIETTIVI

Primario:

-Prevalenza di sarcopenia nei tre diversi

setting assistenziali (ospedale per acuti,

residenza sanitaria assistenziale - RSA,

ambulatorio).

Citation Method Population Sex n. Age

(years)

Prev.

%

Baumgartner

et al,1998

Antro-

pometric

Rosetta study M

F

883 61–70

71–80

≥80

13

24

50

Janssen

et al, 2002

BIA NHANES III M

F

2224

2278

60

60

7

10

Newman

et al, 2003

DXA HABC M

F

1435

1549

70-79 20

20

Jansson

et al, 2004

BIA Cardiovascular

Health Study

M

F

2196

2840

65 17

11

International Working Group on Sarcopenia, JAMDA 2012

SARCOPENIA PREVALENCE

60-79 years = 7-20%

80 years = 50% what about different settings?



57° Congrsso

SIGG

OBIETTIVI

SAMPLE SIZE: - Considerando come “outcome primario” la prevalenza di

sarcopenia nei pazienti in ricovero per acuto ed assumendo

una prevalenza di sarcopenia pari al 30% (CI 95% 25-35), è

necessario un campione di 323 pazienti .

- Per essere certi del risultato previsto, il numero di pazienti

sarà aumentato del 50% con un campione finale costituto da

484 pazienti (484/6=81 pazienti per unità operativa).

n=484



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Incidenza di declino funzionale (perdita

di almeno n. 1 attività di base della vita

quotidiana - ADL) ad un anno nel

ricovero per acuto, in RSA ed in regime

ambulatoriale;

Disability associated with obesity, sarcopenia, and

sarcopenic-obesity in elderly women: EPIDOS (EPIDemiologie de l’OSteoporose) Study

Od

ds r

ati

o

Sarcopenic

Obese

Sarcopenic-obese

Rolland Y et al., Am J Clin Nutr 2009

AD

L l

ost 1

(%

) Sarcopenia and Activity Daily living lost

Preliminary results -1 year follow-up

Abete P et al, unpublished results

Caratteristics

(n=120)

Age (y) 74.8

BMI (kg/m2) 21.5

MMSE 22.2

CIRS-S 1.9

GDS 4.2

PASE 72.4



57° Congrsso

SIGG

OBIETTIVI

SAMPLE SIZE: Considerando come “outcome secondario” l'incidenza di

declino funzionale (perdita di ≥ 1 ADL a 12 mesi), con un

rischio relativo di 2.00, con un potere dello studio 85%:

- ambulatorio (prevalenza 20%)= 392 pz

- pazienti in ricovero per acuto (prevalenza 30%) = 322 pz

- RSA (prevalenza 35%)= 304 pz

n=1018



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Mortalità

Sarcopenia and mortality among older

nursing home residents.

Landi F et al., JAMDA 2012

subjects (n = 122) aged 70 years and older who lived in the teaching

nursing home

log-rank test (p<0.001)

adjusted HR 2.34; 95% CI 1.04–5.24.

No sarcopenia

Sarcopenia

SU

RV

IVA

L



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Incidenza di sarcopenia nel ricovero per

acuto

- Ospedalizzazioni;

- Durata della degenza

- Consumo di risorse

Summary score (0-4)

- grip strength

- knee strength

- walking speed

- chair stands

Age, race, sex

Multivariate

+ muscle density

Od

ds r

ati

o

SUMMARY SCORE

Risk of hospitalization according to Summary

Physical Performance Score in older adults

Cawthon PM et al., JAGS 2009

Days n

um

ber

Days in hospital according to quartile of muscle

density

Cawthon PM et al., JAGS 2009

Least Dense Muscle Most Dense Muscle



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Rilevazione dei fattori di rischio per

sarcopenia

Comparison of anthropometric, lifestyle, and hormonal

variables between men with sarcopenia defined as a relative

appendicular skeletal muscle mass index (RASM)

Variable Normal

RASM

(>6.32 kg/m)

Low

RASM

(<6.32 kg/m)

Age (y) 63±8 67±9

BMI (kg/m2) 28.9±3.5 25.0±2.6*

Smokers (%) 12 17 *

Leisure time physical activity 22±13 18±11*

Free Testosterone (nmol/L) 208±80 190 ±75*

Free Testosterone index 0.25±0.09 0.22±0.11*

Szulc P et al., Am J Clin Nutr 2004 *p<0.05 vs normal RASM



57° Congrsso

SIGG

OBIETTIVI

Secondari:

-Cadute

Muscle weakness and falls in older adult

Moreland JD et al., JAGS 2004

3.06 (1.86-5.04) 1.52 (1.05-2.20)



57° Congrsso

SIGG

OBIETTIVI

Secondari:

-Validazione della diagnosi di sarcopenia

mediante Risonanza Magnetica Nucleare

Cray G et al, Clinical nutrition 2011

Magnetic resonance imaging in

sarcopenia/cancer cachexia

healthy woman aged 23 y

healthy woman aged 80 y (SARCOPENIA)

woman with upper GI “cancer” aged 75 yr

(CACHEXIA)



57° Congrsso

SIGG

OBIETTIVI

Secondari:

-Identificazione di marcatori di deficit

ormonali e/o nutrizionali (albumina, vit.

D, testosterone, FT3, FT4, ect.)

Risk of substantial decline in muscle strength

over 3 years according to sex-specific quartiles of

serum albumin concentration (g/L)

Women

1. < 43.0 g/L;

2. 43.1–44.6 g/L;

3. 44.7–47.1 g/L;

4. > 47.1 g/L.

Men

1. < 43.0 g/L;

2. 43.1–45.0 g/L;

3. 45.1–47.0 g/L;

4. > 47.0 g/L.

Schalk BWM et al., JAGS 2005

Age-adjusted relations between sexual hormone

levels and sarcopenia

Maximum

extension

strength

maximum

handgrip

strengt

P

Total testosterone/SHBG 0.193 -0.021 <0.001

Free testosterone; 0.178 -0.017 <0.01

Estradiol (E2, pmol/l) -0.014 -0.005 0.56 (NS)

Tineke AC et al., European Journal of Endocrinology 2009

0

20

40

60

80

100

Euthiroyd Sublinical hypo Overtly hypo

Muscle mass and prevalence of sarcopenia

according to the thyroid functional status

*p<0.05 vs.euthyroid

Sarcopenia (prevalence%)

Moon MK et al., J Korean Med Sc 2010

* *

FT3

(pg/ml)

3.35

(0.64)

2.55

(0.59)

<0.001

FT4

(ng/dl)

1.32

(0.26)

1.25

(0.23)

<0.001

TSH

(μlU/ml)

1.39

(0.86)

1.54

(0.89)

<0.001

Corsonello A et al., Age & Ageing 2010



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Identificazione di biomarcatori specifici

di sarcopenia (biomarcatori

infiammatori, sirtuine);

Schaap LA et al., Am J Med 2006

Interleukin-6 (IL-6) and C-reactive protein (CRP)

and risk of muscle strength loss

“SIRT1” signaling as potential modulator of

skeletal muscle diseases

Tonkin J et al., Current Opinion in Pharmacology

Increased muscle PGC-1 expression protects from

sarcopenia and metabolic disease during aging

Wenz T et al., PNAS 2009

Hand-Grip = 23.7 kg = not SARCOPENIC

CHE = 7.679 U/L (v.n. 5.400-13.200)

SARCOPENIC Hand-Grip = 3.75 kg =

CHE = 2917 U/L (v.n. 5.400-13.200)

Linear regression between grip strenght,

muscle mass and (A) e butyrryl-colinesterase

and muscle mass (B)

Magliocca A et al., SIGG 2012



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Identificazione del meccanismo della

sarcopenia (insulino-resistenza…).

Sarcopenia Exacerbates Obesity-Associated

Insulin Resistance and Dysglycemia: National Health and Nutrition Examination Survey III

Srikanthan P et al., Plos One 2010

Sarcopenia without obesity

Obesity without sarcopenia

Sarcopenic obesity

Insulin resistance HOMA-IR ratio

1.0 1.5 2.0 2.5



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Identificazione del meccanismo della

sarcopenia (…riduzione del

meccanismo di autofagia a livello

biomolecolare).

tissue lost

↑ APOPTOSIS

regeneration deficit

↓ AUTOPHAGY

CALCIUM OVERLOAD

Molecular mechanisms involved in sarcopenia Conversation between apoptosis and autophagy:

„„Is it your turn or mine?‟‟

Lum JJ et al., Nature 2005

Skeletal muscle autophagy and apoptosis during

aging: effects of calorie restriction and exercise

Wohlgemuth SE et al., Exp Gerontol 2009

Y-AL =youg ad libitum

O-AL =old ad libitum

O-CR =old caloric restricted

O-CREX=old caloric restricted exercised

a = p<0.01

b = p<0.05

APOPTOTIC INDEX AUTOPHAGIC INDEX

Guido S et al., Nature 2010

Is autophagy reduced in sarcopenic patients ?

Micro-biopsy



57° Congrsso

SIGG

OBIETTIVI

Secondari:

- Identificazione di polimorfismi genetici

associati alla sarcopenia.

Polymorphic Variation in the Human Myostatin

Gene is associated with accelerated sarcopenia

“Women’s Health Aging

Study II”

Seibert MJ et al, JAGS 2001

*

Mu

scle

str

en

gth

(Kg

)

p<0.05 vs KK

“Chianti Study”

Corsi AM et al, JAGS 2002

Mu

scle

str

en

gth

(Kg

)

*

mTOR regulation of autophagy This protein kinase plays a key role in autophagy in response to

nutritional status, growth factor and stress signals.



57° Congrsso

SIGG

GRUPPO DI LAVORO ITALIANO

SULLA SARCOPENIA

57 Congresso SIGG · 57° Congresso SIGG MiCo – Milano Convention Center 21/11/2012 - 24/11/2012...

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Transcript of 57 Congresso SIGG · 57° Congresso SIGG MiCo – Milano Convention Center 21/11/2012 - 24/11/2012...