2011

.


..

 2011

 1989 2010

etabolic syndrome
Insulin resistance syndrome
Syndrome X
Diabesity
Deadly quartet
Plurimetabolic syndrome
Dysmetabolic syndrome
CHAOS syndrome
Dysmetabolic syndrome X (277.7 ICDICD-9)

Metabolic Syndrome: Definition

The metabolic syndrome is a clustering

of factors associated with an increased
risk for atherosclerotic cardiovascular
disease (ASCVD) and diabetes.

Grundy, S. M. et al. Diagnosis and management of the metabolic syndrome.

An American Heart Association/National Heart, Lung, and Blood Institute
Scientific Statement. Circulation, 2005, 112: 27352752

- HDL-C
LDL
=





(plasminogen activator
inhibitor-1, PAI-1)


(ICAM, VCAM)
M
ADMA

CRP, TNF-a, IL-6

resistin, adiponectin

Meigs JB. The metabolic syndrome. BMJ 2003;327: 61

Eckel R, Grundy S, Zimett P. Lancet 2005; 365: 1415

;


Statement AHA -NHLBI
(3 5
)

1.

102 cm ()
()
88 ()

2.

150mg/dl
150mg/dl
TG

3. HDL

<40 mg/dl ()
()
<50 mg/dl ()
DL
DL

4.

130/ 85 mmHg
/

5.

100 mg/dl

Circulation 2005
2005; 11
112:
2: 2735 - 52


IDF, NHLBI, WHF, IAS, AHA 2005,
2005,2009
2009

/
.
94cm
80cm (DF)

A
. G

150mg/dL

HDL
HDL

<40mg/dL < 50mg/dL

.. 130mm / . .
85mm Hg

100mg/dL

Circulation 2009

A. Melidonis et al. Cardiovascular Diabetology 2006;5:212006;5:21-27

To .
.
800

(>150 mg%)

(AUC
(AUC 0.786).
0.786).


HDL (AUC 0.805 0.801
).

). Waist

Melidonis A. et al Cardiovascular Diabetol

Diabetol.. 2006; 4: 5: 21

11

16

Pasquale Strazzullo et al, Metabolism Clinical and Experimental 57

(2008) 355
355361


.

Olivetti heart study

Strazzullo et al. Metabolism Clinical and Experimental 57 (2008) 355

355361


--
NCEP--AHA/NHLBI vs IDF
NCEP
IDF--EASD
EASD--EAS

NCEP

AHA/NHLBI

IDF

N=9,669

70

*=p<0.0001

60

*=p<0.0001

50
40

*
*

30

20

10
0
18-70+

18-29

30-39

40-49

50-59

60-69

70+

Athyros et al. Curr Med Res Opin 2005;21:1157-9.

Athyros et al. Int J Cardiol 2006

MGSD ARIC

NHANES

. .

22.2

23.6

27.2

-----

24.1

34.8

56.8

27.9

63.0

55.0

33.4

37.6

51.3

30.0

62.5

24.3

25.7

26.5

10.0

42.8

HDL

34.8

24.7

75.2

24.0

39.5

12.4

18.2

5.5

42.0

27.2

 1




,

 2011.

 2011

WHR
BMI
Adiponectin
Leptin

Blood
pressure

Sodium retention
Sympathetic NS activation
Endothelial dysfunction

Dyslipidemia
Central
obesity

Metabolic
syndrome

LDL-C
LDLHDL--C
HDL
TG
Apo B
Signal dense
LDL particles

Sleep
apnea
Sympathetic tone

PCOS
Insulin
NAFLD
resistance
T2DM
Fasting Insulin
Fasting Glargine

Florinogen
CRP
IL--6
IL
Aciponectin

Systemic
inflammation

PAI-I
PAITNF--x
TNF
Fibrinolysis

JA Batsis et al, Clinical Pharmacology and therapeutics 2008;82:509

RBP4

A
( D)

IF
IL-1, 4, 6, 8, 10, 18

TNF
FF

PAI-1

FABP (aP2)

LPL ApoE

()- CP-1

Deng & Scherer Ann N Y Acad Sci 2010;1212:E1-E19

Ang II

PAIPAI
-1

ACE

TNFa

Insulin Resistance and Cardiovascular Disease
Brent M. Egan et al. AJH 2001; 14:116S
14:116S125S

 ,
,

Jose Manuel Ferna

Jose
Ferna ndez
ndez--Real1 and John C. Pickup2, Trends in Endocrinology and Metabolism, 2008; 19(1):10

Vessel and metabolic actions of insulin in healthy individuals

and CVD patients

JNK

JNK

Seung Hwan Han et al. JACC 2007

2007;; Vol. 49, No. 5 : 531
531
8

Dandona et al. Circulation 2005; 111: 1448

Visceral Obesity and atherosclerosis

Macrophage
infiltration

Adipose
Tissue
(VAT
VAT))

Free Fatty
Acids
Acids

Cytokines
Cytokines

Adiponectin
Adiponectin

Inflammation

Insulin resistance

etab.Syn
drome-drome
Diabetes

Atherogenesis
Ydkin, ECO 2005

H

Genetic variation

Environmental factors

Abdominal obesity
Adipokines

Adipocyte

Cytokines
Inflammatory markers
Insulin resistance

Tg

Metabolic syndrome

Monocyte/
macrophage

HDL

BP
Atherosclerosis

Plaque rupture/thrombosis

Cardiovascular events

Reilly &Rader Circulation 2003; 108:1546 -51

Eckel et al Lancet. 2005; 365: 14151415- 28

ANTI - -
STRESS

RAS
SNS

Leptin

Nutrition
Age
Genes
Fetal programming
Race

Atherosclerosis

Adipose tissue
Brain

Cytokines

SNS

Beta cell
Liver

Inflammation

Acute
phase proteins

ACTH

Acute phase
response

F
Insulin
resistance

CRP
Fibrinogen
Serum amyloid A
PAI -1
tPA
Complement

HDL

Cortisol
Glucose
Intolerance
Central obesity

Hypertension

Insulin
resistance

Black et al. Brain Behav Immun. 2003; 17:35017:350- 364

Pathogenesis of MetS: Insulin resistance

Insulin resistance

Compensatory
hyperinsulinemia to maintain
euglycemia, especially
postprandially

Obesity (appetite stimulation?)

-cell failure and diabetes
Overstimulation of MAP kinase
pathway
Dyslipidemia due to high FA flux

Metabolic Syndrome
Increased atherosclerosis and
CVD
Miranda PJ, DeFronzo R et al. Am Heart J, 2005, 149:33149:33-45

 2011.

 2011

 (..)

.;
..

;

..
..
..

;



Kuopio study

20

20

20

15

15

Cumulative Hazard, %

15

RR (95% CI), 2.43 (1.64

(1.64--3.51)

10

10

10

0
0

No. at Risk
.
Yes
No

RR (95% CI), 3.55 (1.96

(1.96--6.43)

RR (95% CI), 3.77 (1.74

(1.74--8.17)

866
867

4
6
8
10
,, y

852
279

834
234

292
100

12

0
0

866
288

4
6
8 10
, y

852
279

834
234

12

292
100

866
288

4
6
8 10
, y

852
279

834
234

12

292
100

*NCEP ATP III.

Lakka H, et al. JAMA. 2002;288:2709
2002;288:2709--2716.

 CV (H
(H R,
95% CI)
ULSAM study: 1758 . Fu=30

.
.

.
.

1.28
(0.90 1.82)

1.21
(1.03 1.40)

1.53
(1.19 1.96)

1.65
(1.03 2.66)

2.43
(1.81 3.27)

CV

1.77
(1.11 2.83)

1.44
(1.14 183)

2.19
(1.57 3.06)

1.20
(0.49 2.93)

3.20
(2.12 4..82)

CV

1.63
(1.11 2.37)

1.52
(1.28 1.80)

1.74
(1.32 2.30)

1.95
(1.14 3.34)

2.55
(1.82 3.58)

Lancet 2009;373:1844-1860

To

591 . Fu = 10,1

HR

95% CI

P value

1.166

0.801--2.044
0.801

0.113

(cm
(cm))

1.011

1.009--1.049
1.009

0.002

. . (mm/Hg
mm/Hg))

1.032

0.900--1.153
0.900

0.033

HDL (mg/dl
mg/dl))

0.978

1.003--1.039
1.003

0.031

A. . .

1.020

0.822--1.265
0.822

0.858

1.009

1.005--1.048
1.005

0.002

(cm)

Protopsaltis J, Melidonis A et al. Stroke 2008;39:10362008;39:1036-1038


/
37 , 17200

Gami A.S., Journal of the American College of Cardiology Vol. 49, No. 4, 2007


87 951083

(
)

.
(
)

2.35
(
)

2.40

1.58

1.99

2.27

. NCEP
2001
o
o

2.51

1.85

1.54

1.69

2.43

(2004) NCEP
..

1.93

2.91

1.63

1.97

2.92

--

1.75

1.32

1.62

1.86

Mottilo S., Filion KB, Genest et al J Am Coll Cardiol 2010;56:11132010;56:1113-1132

( . .
)

Gami A.S., Journal of the American College of Cardiology Vol. 49, No. 4, 2007

NHANES study

T
HDL

1.13
1.12
1.74 *
1.87 *
0.96
1.55 *
0.94

*
Alexander CM et al Diabetes, Vol. 52, 2003; 1210-1214

 (..)

(NHANES STUDY: 6255 , FU: 13,5
))

HR

HR

HR

..,
..,
,, CVD

2878

1.0

1.0

1.0

..((
..
))

1698

2.02

0.0001

1.82

0.005

1.40

0.0001

1178

1.65

0.02

1.56

<0.0001

1.17

0.11

520

2.87

<0.0001

2.42

<0.0001

1.97

<0.0001

..((
..
))

..
..((
))

alik S. et al. Circulation 2004

2004; 11
110
0: 1245
1245--50

H
(S
(S)
Framingham offspring study,
study, 2800 , FU: 11

MS with ATP III

MS with IDF
MS with EGIR

JAMES B. MEIGS, Diabetes Care 30:1219

30:1219
25, 2007

.

,
,

.

 (..)

.;
..

;

..
..
..?
..

;

O


4350 , FU: 7,1

(H.R= 2.5 ,
P<0.001)

(H.R= 2.3 ,
P<0.001)

(H.R= 0.78 ,
P=0.48)

T. S. Church et al, Diabetes Care 2009;32:12892009;32:1289-1294


(.)
.
62.000
62
.000 Fu = 3,57
3,57

Diabetes Care 30:2381

30:2381
2387, 2007




600 , : 10

HDL
(Hazard
(Hazard Ratio=1,791).

Protopsaltis I, Melidonis A,
A, et al, Atherosclerosis 195 (2007) 189
189194
194..


..

.. IDF,
..
. .
..

..


.

 (..)


.;
..

;

..

...
.
..

;

TO METABO
METABO
/
FRAMINGHAM SCORE;
San Antonio Heart Study
2570 CVD
CVD,, 7
aROC
Framingham score

0.816

Framingham score
+ metabolic syndrome

0.811

Framingham score CVD
CVD..
Stent et al. Diab Care 2004; 27: 2676 -81
Mergs (Editorial) : Diab Care 2004; 27: 2761

..


.

 2011.

( )

 2011

(
)

(
)

lberti 2005;

 ADA EASD


,
,
,

..

.

Statement ADA and EASD

Diabetes Care 2005; 28: 2289 -2304

Kahn R. Diabetes Care 2006;
2006; 29:1693
29:1693--1696



Statement AHA -NHLBI

:
:
: LDL

High risk <100 mg/dl

Very high risk + <70 mg/dl
high risk+
risk+ <13
130
0 mg/dl

: non HDL Very high risk + <100 mg/dl

high risk + < 13
130
0 mg/dl
: HDL

Lifestyle . HDL

.:

<140/ 90 mmHg & <130/ 80

. .
.

IFG lifestyle .
. . . 1C
1C <7%.

.
CVD clopidogrel
.
Circulation 2008
2008; 11
112:
2: 2735

 2011.

( )

 2011

(scores)

F. Ferrannini JCEM 2007;92:396

Insulin Resistance, Cardiovascular Disease, and the

Metabolic Syndrome
How well do the emperors clothes fit?
Gerald M. Reaven
the greatest potential drawback is to focus on whether a patient
has the metabolic syndrome rather than addressing abnormalities
associated with insulin resistance and compensatory
hyperinsulinemia..
hyperinsulinemia
emphasizes

the need to implement appropriate

therapeutic intervention to reduce the CVD risk
associated with insulin resistance, irrespective
of the number of ATP III criteria satisfied.
satisfied.
Diabetes Care 2004; 27:101127:1011-1012.

 2010
Rest in peace

 2010
( WHO)

(premorbid)
(premorbid)

Diabetologia 2010


1988
1996 2003
2005

2010
WHO

..it has limited practical utility as a diagnostic or

disease management tool and it should not be ranked as a
clinical diagnosis

Diabetologia

Our best wishes for the Metabolic

Syndrometherefore should be: Rest

in peace!

!!!!

 2011.

( )


87 951083

(
)

.
2.35 risk estimates
2.40 than before,
1.58
We found higher
(
(
metabolic syndrome
is a more serious condition
)

1.99
2.27
suggesting
that
than we previously

thought

. NCEP
2001

2.51

1.85

1.54

(2004) NCEP

1.93

2.91

--

.75

1.69

2.43

1.63

1.97

2.92

1.32

1.62

1.86

Pr. Eisenberg
Mc Gill University

Mottilo S., Filion KB, Genest et al J Am Coll Cardiol 2010;56:11132010;56:1113-1132

 DPP
DPP--4

Diabetes 2011;60:1917
2011;60:1917--1925

 DPP
DPP--4

Vis: viscelar
Sub: subcutaneous

Diabetes 2011;60:1917
2011;60:1917--1925

 DPP
DPP--4 (
) Akt

Diabetes 2011;60:1917
2011;60:1917--1925

 DPP
DPP--4

Diabetes 2011;60:1917
2011;60:1917--1925

Alberti 2011

Final Comment

Metabolic syndrome remains alive and well

It continues to be a useful tool to focus CVD and
diabetes risk
It comprises a simple diagnostic set capable of
use in primary care world wide

Metabolic Syndrome as a
Risk Condition
(Framingham Heart Study)

-Men: RR 2.50 x increased

Cardiovascular disease
- Women: RR 1.58 x increased

-Men: RR 4.76 x increased

Type 2 Diabetes
- Women: RR 5.66 x increased

Alberti 2011

To
.
,
.

(.. 10 ) , Framingham risk
scoring.
..
/ .
.
/
.


.
.

Grundy S. JACC 2006; 47: 1093

Grundy S. Diabetes Care 2006 29:168929:1689-1692

ahn R Lancet 2008;371:1892

 !
, !!!

 2010
( WHO)

(premorbid)
(premorbid)

Diabetologia Apr. 2010

++

++

, & .

++

++

++

++

1111-HSD

++

++

++

IL
IL--6, ILIL-8, PAIPAI-1, .

+++

- / &

++

PPAR
PPAR

++

++/+++

2 .

( JNK, p38MAPK, IKK,

ERK, JNK p38 MAPK

Wajchenberg BL Endocr Rev 2000;21:6972000;21:697-738, Yang X et al. Diabetologia 2007;50:1127

2007;50:1127--39


TG
VLDL

LPL
CETP

TG, HDL,
LDL

FF

Heilbronn et al Int J Obes 2004;28:12

2004;28:12--21
21,, Carr et al J Clin Endocrinol Met
Metab
ab 2004;89:2601
2004;89:2601--7, Eckel et al. Lancet 2005;365:1415
2005;365:1415--28



INTERHEART study

Mente et al. JACC 2010;55(21):23902010;55(21):2390-2397



INTERHEART STUDY

 11 HSD1

JCEM 2009;94:46452009;94:4645-4654

 KAI

-/
Standl E. et al. Eur. Heart J. 2005; 7: D10
D10--13



34179

n=34179

T. S. Church et al, Diabetes Care 2009;32:12892009;32:1289-1294

 , ,

(NHANES 19991999- 2000: 3873 )
Odds ratio
of CVD

Malik S. et al. Diabetes Care 2005; 28: 692

Diabetologia 2010;53:2
2010;53:2105
105--2111

 concept

Diabetologia 2010;53:2
2010;53:2105
105--2111

Van Gaal L. Mertens I. De Block C; Nature 2006

 CVD
CVD
Framingham Heart Study

PW Wilson, RB DAgostino, H. Parise et al Circulation 2005;112:30662005;112:3066-3072

Diabetes Care 2011;34(suppl. 2):s171

2):s171---s1
s176
76

 2011.

( )