DYSLIPIDEMIE DU DIABETE TYPE 22 3 100 160 220 85 65 45 25 HDL-C is a potent risk factor for heart disease: The Framingham Study LDL-C, mg/dL HDL-C, mg/dL Risk of CHD *Men 50 to 70

DYSLIPIDEMIE DU DIABETE TYPE 2

Pr. N. OuadahiMédecine interneCHU Bab El Oued

6° Forum National de l’OmnipraticienAlger le 8 Avril 2010

WH

O R

epor

t 199

7. W

orld

Hea

lth O

rgan

isat

ion.

Gen

eva

1997

40

15 13 1310

4 5

0

10

20

30

40

50

Ische

mic

heart

dise

ase

Other h

eart

disea

se

Diabete

s

Malign

ant

neop

lasms

Cerebro

vasc

ular

disea

se

Pneum

onia/

influe

nza

All othe

r

De a

ths

(%)

Causes of death in people with diabetes

Probability of Death From CHD in Patients With Type 2 Diabetes With

or Without Previous MI

Diabetics: a risk of death from CHD 3 times higher in post-MI patients

Mortality rate at 7 years

15.42.1

42

15.9

0

10

20

30

40

50

Diabetics Non-diabetics

%No previous MI

Previous MI

Haffner SM: NEJM 1998;330:229-234

X 3

De multiples FDR à l’origine des événements CV

Antécédents CV

Sexe

Age

Obésité androïde

Diabete

Dyslipidémie

Hypertension Tabac

High CRP Alimentation

Mortalité CVMortalité CV

Chez le diabètique, la dyslipidémie occupe une place centrale, en raison de son profil particulier.

UKPDS: Typical Lipid Profile in Patients with Diabetes Compared with No Diabetes

UKPDS. Diabetes Care 1997;20:1683-1687.

5

5,2

5,4

5,6

5,8

6

Total cholesterol mmol/L (mg/dL)

MenMen

WomenWomen

DT2non D

non D DT2

3

3,2

3,4

3,6

3,8

4

LDL-C mmol/L (mg/dL)

p<0.001

MenMen

DT2non D

non D DT2

WomenWomen

(193)

(232)

(224)

(216)

(208)

(201)

(116)

(124)

(131)

(139)

(147)

(154)

UKPDS: Typical Lipid Profile in Patients with Diabetes Compared with No Diabetes

UKPDS. Diabetes Care 1997;20:1683-1687.

1

1,2

1,4

1,6

1,8

2

Triglycerides (mmol/L)

p<0.001 p<0.001

MenMen WomenWomen

non D

DT2 DT2non D

1

1,2

1,4

1,6

HDL-C mmol/L (mg/dL)

DT2 DT2non D

non D

p<0.02

p<0.001

MenMen

WomenWomen

(39)

(46)

(54)

(62) (177)

(159)

(142)

(124)

(106)

(89)

Slide SourceLipidsOnline

www.lipidsonline.org

Dyslipidemies chez les adultes diabétiques.Dyslipidemies chez les adultes diabétiques.Framingham Heart StudyFramingham Heart Study

↑ cholesterol

↑ LDL

↓ HDL

↑ Triglycerides

NormalNormal DD NormalNormal DD

14%

11%

12%

9%

13%

9%

21%

19%

MM FF

21%

16%

10%

8%

24%

15%

25%

17%

Garg A et al. Diabetes Care 1990;13:153-169.

Augmentation Augmentation

Profil lipidique caractéristique du diabète de type 2

Diminution Diminution

Triglycerides

VLDL

LDL petites et denses

Apo B

HDL

Apo A-I

L’apoprotéine B, très abondante dans les LDL: marqueur du courant d’influx ;

l’apoprotéine AI, liée préférentiellement aux HDL: marqueur du courant de retour du cholestéro

VLDL

Rchylo

IDL LDL

CHOLESTEROL

ApoB

CHOLESTEROL

HDL Apo A

Entrée

Sortie



DyslipidemieDyslipidemie du Diabete type 2 du Diabete type 2

↓ HDL-C

± LDL LDL Petite

& Dense↑ TG



HDLHDL

0

1

2

3

100 160 220 8565

4525

HDL-C is a potent risk factor for heart disease: The Framingham Study

LDL-C, mg/dL

HDL-C, mg/dL

Ris

k of

CH

D

*Men 50 to 70 years of age Gordon T et al. Am J Med 1977;62:707-14.

3

2

1

4Equivalent RiskEquivalent Risk

Les triglycérides

TG Level Is Significant CVD Risk Factor: Recent Meta-Analysis of 29 Studies

Sarwar N, et al. Circulation. 2007;115:450-458.

*Individuals in top vs bottom third of usual log-TG values; adjusted for at least age, sex, smoking status, and lipid concentrations; also adjusted for BP (in most studies).

CHD Risk Ratio* (95% CI)

1.72 (1.56-1.90)21

Duration of follow-up≥10 years 5902<10 years 4256

SexMale 7728Female 1994Fasting statusFasting 7484

Nonfasting 2674Adjusted for HDLYes 4469No 5689

N = 262,525Groups CHD Cases




Sous classe phénotypique des LDL et Sous classe phénotypique des LDL et diabètediabète

Men*Men* Diabetic Nondiabetic

Women**Women** Diabetic Nondiabetic

** Selby JV et al. Circulation 1993; 88:381-387.

IntInt BB

* Feingold KR et al. Arterioscler Thromb 1992; 12:1496-1502.

2987

54543

2847

3485

2129

309

5124

366

LDL SubclassLDL Subclass

nn AA

PercentPercent

LDL size (Å)

LDL

chol

este

rol (

mm

ol/l) r=-0.01

n=299

Relationship between LDL particle sizeand LDL cholesterol

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0270265260255250245240235

From Després JPAnn Med (2001) 33:534-541

M. Austin JAMA 1988; 269: 1916

““Normal” LDL-C in people with impaired LPL can be misleading...Normal” LDL-C in people with impaired LPL can be misleading...small, dense LDL-C particles present in people with impaired LPLsmall, dense LDL-C particles present in people with impaired LPL

are more atherogenic than normal LDL-Care more atherogenic than normal LDL-C

Lower CHD risk Higher

‘Normal’ LDL-cholesterol

Normal LPLLDL particles

Impaired LPLLDL particles

‘Normal’ LDL-cholesterolhowever:

Number of LDL-C particlesConcentration of Apo-B

Small, dense LDL-C with more Apo-B

• Apo-B• LDL-C

Atherogenicité des LDL petites et densesAtherogenicité des LDL petites et denses

Penetration

Small LDL particles penetrate arterial intima more readily, are retained preferentially, and are more susceptible to oxidation,

leading to enhanced macrophage uptake and foam cell formation.

Macrophage uptake

High proteoglycan

binding affinity

Accelerated oxidation

VESSEL LUMENEndothelial Cells

Small LDL

ARTERIAL INTIMA

Large LDL

FOAM CELL LESION

LDL diameter vs plasma TGLDL diameter vs plasma TG

R= –0.88

28

27

26

25

24

23 0 1 2 3 4 5 6Plasma TG (mmol/l)

LDL

diam

eter

(nm

)

Scheffer et al. Clin Chem 1997;43:1904–12

Les lipoprotéines athérogènesLes lipoprotéines athérogènes

- Lipoprotéines riches en TG - Lipoprotéines riches en TG

VLDLVLDLVLDLVLDLRR

IDLIDLLDLLDL

Small,Small,densedenseLDLLDL


Quelle sera la stratégie Quelle sera la stratégie thérapeutique ? thérapeutique ?

Les règles d’hygiène de vie sont Les règles d’hygiène de vie sont en première ligne et seront en première ligne et seront poursuivies indéfiniment. poursuivies indéfiniment.

Quels sont les objectifs Quels sont les objectifs thérapeutiques selon les thérapeutiques selon les

recommandations ? recommandations ?

Calcul du non HDL c:

Non HDL c = Cholestérol Total – HDL c

Détermination de son objectif:

Objectif non HDL c = Objectif LDL c + 30 mg/l

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

Calcul du non – HDL c et détermination de son objectif

Joint European Societies’ recommendations for lipid management.

Lipid management to aggressively lowercardiovascular disease in high-risk type 2 diabetes mellitus*

ADA Standards of Medical Care in Diabetes:ADA Standards of Medical Care in Diabetes:Dyslipidemia ManagementDyslipidemia Management

First Priority Second Priority

LDL-C LoweringGoal: <100 mg/dL*

TLC Statins

Niacin, ezetimibe, bile acid sequestrants, or fenofibrate

HDL-C RaisingGoal: >40 mg/dL†

TLC Niacin‡ or fibrates

TG LoweringGoal: <150 mg/dL

TLC Glycemic control

Fibrates (fenofibrate, gemfibrozil) Niacin‡

Statins (if LDL-C is also high)

CombinedHyperlipidemia

Glycemic control + high-dose statin

Glycemic control + statin + fibrate Glycemic control + statin + niacin‡

American Diabetes Association. Diabetes Care. 2004;27:S68-S71.American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4-S41.

*An LDL-C goal <70 mg/dL is an option in patients with overt CVD. †An HDL-C goal >50 mg/dL should be considered for women. ‡At high doses, niacin may increase blood glucose levels.

ConclusionConclusion

Vive laVive la Formation Médicale Formation Médicale

Continue !Continue !

Documents

DYSLIPIDEMIE DU DIABETE TYPE 22 3 100 160 220 85 65 45 25 HDL-C is a potent risk factor for heart disease: The Framingham Study LDL-C, mg/dL HDL-C, mg/dL Risk of CHD *Men 50 to 70