Transcript Diapositiva 1 - Progetto LIBRA

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Diabetes obesity in patients with COPD
Angelo Avogaro
Intra-abdominal Obesity, Metabolic Risk
Factors and CHD
Atherogenic dyslipidemia
 Triglycerides
 HDL-cholesterol
 Cholesterol/HDL-cholesterol ratio
"Normal" LDL-cholesterol but  apo B
Small, dense LDL and HDL
Postprandial hyperlipidemia
Insulin resistance
Insulin resistance
Hyperinsulinemia
Hyperglycemia
Type 2 diabetes
Thrombotic state
 PAI-1
 Fibrinogen
Inflammatory state
 CRP
 Cytokines
Abdominal obesity
Metabolic risk factors
Inflammation
Lipid core
Thin fibrous cap
CORONARY ATHEROSCLEROSIS
UNSTABLE PLAQUE
 risk of acute
coronary syndrome
adapted from Despres, 2004
Adverse cardiometabolic effects of
products of adipocytes
↑ Lipoprotein lipase
↑ Agiotensinogen
↑ IL-6
Inflammation
Hypertension
↑ Insulin
↑ TNFα
Adipose
tissue
↑ Adipsin
(Complement D)
↓ Adiponectin
Atherosclerosis
↑ FFA
↑ Resistin
↑ Leptin
↑ Lactate
↑ Plasminogen
activator inhibitor-1
(PAI-1)
Thrombosis
Lyon 2003; Trayhurn et al 2004; Eckel et al 2005
Atherogenic
dyslipidaemia
Type
2 diabetes
2001
COPD Inflammation May Contribute
to Cardiovascular Disease
Rennard. Proc Am Thorac Soc. 2005;2:94-100.
The metabolic syndrome in patients with
chronic obstructive pulmonary disease
38 COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16%
34 control participants matched for age and gender are included in this study.
RESULTS: 47% of COPD patients and 21% of control participants
presented metabolic syndrome.
CONCLUSIONS: The presence of metabolic syndrome is frequent
in patients with COPD who participated in a cardiopulmonary program.
Hence, this population should be considered for screening for the
metabolic syndrome.
Marquis K et al, J Cardiopulm Rehabil. 2005
Peak YJ at al, Metabolism 2010
Log-transformed (log) hs-CRP (A), log interleukin-6 (B), fibrinogen (C), and
physical activity level (D) according to GOLD stages and the absence or presence
of the metabolic syndrome.
Watz H et al. Chest 2009;136:1039-1046
220
200
180
1,3
1
1
160
140
120
100
110
1,3
(1) (2) (3) (4) (5)
Waist girth (cm)
Visceral tissue area (cm2)
Visceral adipose tissue favours systemic
inflammation
1,2
106
102
1
1,2,3
1
98
94
90
Quintiles of PCR
Lemieux I et al. Arterioscler Thromb Vasc Biol 2001;21:961-7.
(1) (2) (3) (4) (5)
Quintiles of PCR
11
Sleep Disorders-Metabolic Syndrome
Sleep Fragmentation
Sleep Deprivation
Sleep
Disorders
Intermittent Hypoxemia
Increased Sympathetic Drive
Metabolic
Syndrome
Homeostasis model assessment in Respiratory
Distress Syndrome
Punjabi, N. M. et al. Am. J. Epidemiol. 2004 160:521-530; doi:10.1093/aje/kwh26
Schematic overview of the distinct steps that comprise
leukocyte transendothelial migration
van Buul, J. D. et al. Arterioscler Thromb Vasc Biol 2004;24:824-833
Risk Factors
Cigarette smoking
Diabetes Mellitus
Hypercholesterolemia
Hypertension
Obesity
Age
Family history of CVD
Gender
Postprandial Hyperglycemia
Rescue Factors
HDL cholesterol
Anti oxidant reserves
Endothelial progenitor cells
Cardiovascular Health
Endothelial cell apoptosis and -regeneration
Regeneration
Apoptosis
Risk factors
EPC
Apoptosis
The biological significance of EPCs
What they are?
HSCs
(Lin-,
Totipotent stem cells
CD34+, CD133+ sca-1+, c-kit+)
Multipotent stem cells
(Lin+/-, CD34+, CD133+/- sca-1+/-, c-kit+)
(Lineage commitment)
Lineage progenitor cells
(Lin+, CD34+/-, CD133- sca-1+/-, c-kit+/-)
(Differentiation)
Mature cells
Endotheliocyte
Fadini et al, Diabetes Care 2007
The clinical significance of EPCs
Disease Marker – Cardiovascular risk
Healthy subjects (r=-0.12; p=0.216)
1200
Predicted
500
CVD subjects (r=-0.34; p=0.003)
450
.
.
1000
At risk subjects (r=-0.61; p<0.001)
CD34 cell count
CD34+ cells
800
600
400
Observed
= 3 components:
diagnosis of MS
400
350
*
300
250
200
*
< 3 components
150
100
200
50
0
0
0
20
40
60
10-year Framingham risk (%)
80
100
None
One
Two
Three
Four
Five
Components of the Metabolic Syndrome
Fadini et al. Eur Heart J 2006
Fadini et al. ATVB 2006
The clinical significance of EPCs
Disease Marker – Pulmonary diseases
RLD
CTRL
All patients
COPD
RLD
.
800
600
500
400
300
COPD
200
100
13
3+
KD
R+
R+
CD
34
+C
D
13
3+
KD
CD
R+
34
+K
D
CD
13
3+
34
+C
D
CD
13
3+
CD
34
+
.
0
CD
Progenitor cell counts
700
Fadini et al. Stem Cells 2006
500
80
.
450
70
Cells /10^6 events
The clinical significance of EPCs
Disease Marker – CVD vs Pulmonary disease
400
Healthy (n=137)
CVD (n=62)
PD (n=35)
60
350
300
50
250
40
200
30
150
R
C
34
+C
D
D
13
3+
K
13
3+
K
D
D
R
R+
D
D
C
34
+C
C
D
C
34
+K
D
13
3+
D
34
+
D
C
+
0
D
0
C
10
13
3+
50
+
20
100
Fadini et al. AJRCMB 2006
Fadini et al. Eur Respir J. 2010