Il Paziente diabetico complesso: dalla epidemiologia al ...
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Diabete e sarcopenia
Il Paziente diabetico complesso: dalla epidemiologia al trattamento
Dipartimento di Scienze Mediche – UNIFE
Dipartimento Medico ad Attività Integrata – OSPFE
Università di Ferrara - ex labore fructus -
Stefano Volpato
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Agenda
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Sarcopenia definitions
Diabetes muscle mass and muscle strenght
Underlying biological mechanisms
Functional impact of sarcopenia in older diabetic patients
Potential treatments
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What is Sarcopenia?
Age-related decline in muscle mass
and strength (weakness)
FAT BONE
MUSCLE MARBLED MUSCLE
25 years 75 years
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Cruz-Jentoft A J et al. Age Ageing 2010;39:412-423
Sarcopenia: operational definitions
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Studensky et al. JGMS 2014;69:547-558
EWGSOP FNIH
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Beas-Jmenenz et al. Rev Andal Med Deporte 2011
Etiopathogenesis and risk factors
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Major population-based studies investigating skeletal muscle mass distribution according to diabetes status
Source: Bianchi & Volpato. Acta Diabetol, 2016 6
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Role of Muscle Mass and Muscle Quality in the Association Between Diabetes and Gait Speed
Characteristics Without
Diabetes
With Diabetes
Diet Hypoglycemic
agents All
N 740 37 58 95
Age (yr), mean ±SD 73.8±6.5 75.4±6.8 72.9±5.7 73.9±6.2
Gender (%)
Female 55.9 37.8 48.3 44.2
BMI (kg/m2), mean ±SD 27.3±3.9 28.7±3.6 28.7±4.4 28.7±4.1*
Physical activity level (%)
Moderate 43.4 48.6 53.4 51.6
High 41.9 37.8 29.3 32.6
Fasting glucose (mmol/l)
mean ±SD 4.94±0.62 7.66±2.41† 8.08±2.22† 7.92±2.29†
Duration of diabetes (yr),
median (IQR) - 0 (0-3) 9.5 (4-20) 5.0 (0-13)
Source: Volpato et al, Diabetes Care, 2012 7
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Lower-limb skeletal muscle characteristics in people with and without diabetes: The InCHIANTI Study
All p adjusted for age and gender
No diabetes No hypoglycemic agents Hypoglycemic agents
45
50
55
60
65
70
75
Calf muscle area Muscle density
(Ncm/kg)
p<.01
p<.05
Source: Volpato et al, Diabetes Care, 2012
(cm2) (mg/cm3)
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Major population-based studies investigating skeletal muscle mass distribution according to diabetes status
Source: Bianchi & Volpato, Acta Diabetol, 2016 9
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Major epidemiologic studies investigating skeletal muscle strenght according to diabetes
Source: De Rekeneire & Volpato, Clinics in Geriatric Medicine, 2014 10
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Decreased Muscle Strength and Quality in Older Adults with Type 2 Diabetes (Health ABC Study)
Without diabetes
Diabetes
Diabetes with
duration 6 yrs
Without diabetes
Diabetes, A1C 8%
Diabetes, A1C > 8%
Source: Park et al, Diabetes 2006 11
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3-year changes in knee extensor strength and muscle quality by diabetes in the Health ABC Study
Muscle strength
-20
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
Kn
ee e
xte
nso
r t
orq
ue (
Nm
)
Muscle quality
-2
-1,8
-1,6
-1,4
-1,2
-1
-0,8
-0,6
-0,4
-0,2
0
Sp
ecif
ic t
orq
ue (
Nm
/kg
)
Source: Park et al, Diabetes Care; 2007
p=0.001 p=0.026
Adjusted for age sex, and race
Fully adjusted Fully adjusted
p=0.034 p=0.018
Adjusted for age sex, and race
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Goodpaster B H et al. J Appl Physiol 2001
Skeletal Muscle Mass fat infiltration according to age and adiposity
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MRI images of the lower limbs of control subjects vs. patients with type 2 diabetes
Healthy 69-yr control 67-yr old diabetic with polyneuropathy
Mid-thigh level
Mid-tibia level
Source: Almurdhi M et al., Diabetes Care, 2016 14
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20
25
30
35
40
45
50
55
60
65
70
75
80
Muscle power Kneeextension
torque
Musclequality
Lower-limb skeletal muscle characteristics in people with and without diabetes: The InCHIANTI Study
All p adjusted for age and gender
No diabetes No hypoglycemic agents Hypoglycemic agents
45
50
55
60
65
70
75
Calf musclearea
Muscledensity
(Ncm/kg)
p<.01
p<.05
Source: Volpato et al, Diabetes Care, 2012
p<.05
p<.01
p<.05
(W)
(Ncm/kg)
(kg/dm2) (cm2) (mg/cm3)
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Sarcopenia ≠ Dynapenia
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Relationship of Diabetes with BMI and Sarcopenia: The Glisten Study
33,2% 31,5%
3,6%
25,0%
0%
10%
20%
30%
40%
50%
BMI ≥30 Diabete
Not Sarcopenia Sarcopenia
17,2%
26,3%
39,5% 38,1%
0%
10%
20%
30%
40%
50%
BMI ≥30 Diabete
Not sarcopenia Sarcopenia
Source: Volpato et al, dati non pubblicati
EWGSOP FNIH
SMI: Appendicular skeletal muscle mass/height2 SMI: Appendicular skeletal muscle mass/BMI
P<001* P<005* P<001*
P=238
*age and gender adjusted
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Potential mechanisms of age-related and disease-related muscle loss
Diabetes Obesity
Source: Kalyani et al, Lancet Diabetes 2014 18
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Pathways of accelerated muscle loss in type 2 diabetes
Source: Kalyani et al, Lancet Diabetes 2014 19
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Source: Andersen et al. Diabetes, 1996
Isokinetic Muscle Strength in Long-Term IDDM Patients in Relation to Diabetic complications
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Diabetes, Peripheral neuropathy and lower extremity function: InChianti Study
Chiles , Volpato et al, JDC 2014;28:91-5 21
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Potential biological mechanism explaining the diabetes-related muscle dysfunction
Bianchi & Volpato. Acta Diabetol, 2016 22
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Cross-sectional and case-control studies
Mobility Disability ADL Disability
Source: Wong et al, Lancet Diab&End; 2013 23
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Longitudinal studies: Mobility Disability
Source: Wong et al, Lancet Diab&End; 2013 24
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Longitudinal studies: ADL Disability
Source: Wong et al, Lancet Diab&End; 2013 25
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Walking disability (walking speed <0.4 m/s) in older women (Women Health and Aging Study)
Prevalence (%)
Source: Volpato S. et al. Diabetes Care; 2002
Adjusted OR: 1.90 (1.24-2.90)
Adjusted for age, race, smoking, education, BMI, knee osteoarthritis, cognitive impairment, depressive symptoms
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0,7
0,8
0,9
1
1,1
1,2
1,3
Age-gender All musclevariables
Fully adjusted
0,7
0,8
0,9
1
1,1
1,2
1,3
Age-gender All musclevariables
Fully adjusted
Association of diabetes and gait speed: Multivariable linear regression analyses
Hypoglycemic agents
No diabetes
No hypoglycemic agents
p<.001
p<.01 p<.05
p=.002
p<.05
p=.01
Muscle variables:
• muscle density
• knee extension torque
• ankle strentgh
• muscle power
• muscle quality
400-m gait speed (m/s)
4-m gait speed (m/s)
Source: Volpato et al, Diabetes Care, 2012 27
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Percent reduction in the association between diabetes and gait speed after adjustment for potential mediators
Source: Volpato et al, Diabetes Care, 2012
4-meter test
400-meter test
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Putative model of the pathway from diabetes to impaired mobility
29 Source: Bianchi & Volpato. Acta Diabetol, 2016
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Potential treatments for age-related and diabetes-related disability and muscle impairment
Diet
High quality protein supplementation?
Strict glycemic control
No evidence available
Risk of hypoglycemia in older people
Insulin sensitizer agents
Thiazolidinediones ?? No evidence available
Exercise
Yes but specific RCT are missing
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31 Source: Pahor M et al. JAMA, 2014
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Effect of Structured Physical Activity on Prevention of Major Mobility
Disability in Older Adults: The LIFE Study Randomized Clinical Trial
Source: Pahor M et al. JAMA, 2014 32
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Conclusions
Diabetes accelerates the age-related declini in muscle strenght
and quality
The mechanism explaining the excess risk of disability in older
diabetic patients is multifactorial, however sarcopenia is an
important mediator linking diabetes to disability
Structured physical activity programs might prevent or
postpone disability onset in older people with diabetes and
sarcopenia
33