ueda2013 diabetic dyslipidaemia-d.khaled

Diabetic Dyslipidaemia BY

بسم هللا الرحمن الرحيم

KHALED EL SAYED EL HADIDY

Professor of Internal Medicine

Beni Sueif University

Consultant of Endocrinology & Diabetes

Is it only the LDL Goals that can solve the

problem of Diabetic Dyslipidaemia?

Agenda

Lipid Pathophysiolog in T2DM.

Dyslipidemia as a CAD. Risk Factor.

Neglected Area in Diabetic Dyslipidaemia .

ADA Standards of Medical Care in Diabetes (2013).

Antilipidemic drugs.

Take Home message.

• Apo A-1

• SD LDL

HDL

Apo A-1

(CETP)

(LACT)

IR-----FFA

TG

Apo B

Proteolysis of Apo B-100

Clearance LPL, APO CIII

HDL (CETP)

(LACT)

Apo A-1

IR-----FFA

TG

Apo B

Proteolysis of Apo B-100


SD

LDL

HDL (CETP)

(LACT)

Apo A-1

(CETP)

• Apo A-1

• SD LDL

HDL

Apo A-1

(CETP)

(LACT) Proteolysis of Apo B-100


TG

Apo B

IR-----FFA

SD

LDL

↑ Non–HDL

= Total C – HDL-C (all atherogenic lipids)

(CETP)

Agenda

• Lipid Pathophysiolog in T2DM.

• Dyslipidemia as a CAD. Risk Factor.

• Neglected Area in Diabetic Dyslipidaemia .

• ADA Standards of Medical Care in Diabetes (2013).

• Antilipidemic drugs.

• Take Home message.

(Aso. CHD) most common cause

of morbidity and mortality in type 2 DM.

( Aso. accounts for about 80% of all mortality).

(75% due to CHD & 25% due to cerebral or PVD).

`(CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696. 2Third Report of the NCEP Expert Panel on Detection, Evaluation, and Treatment of

High Blood Cholesterol in Adults (ATP III). Circulation. 2002;106:3143-3421.

(NCEP) (ATP) III : patients with diabetes should be

regarded as having CHD risk equivalent to that of patients with

known CHD.

European guidelines : risk of developing an MI is the

same for diabetic patients as it is for nondiabetic patients with a

prior MI.

Therefore, the same aggressive lipid treatment goals

should be applied to both diabetic and CHD patients,

even if the diabetic have no evidence of existing CHD.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15325833















CAD. Risk Factors

Agenda







Non–HDL-C Superior to LDL-C in Predicting CHD Risk

Liu J, et al. Am J Cardiol. 2006;98:1363-1368.

0

0.5

1

1.5

2

2.5

LDL - C mg/dL

Non–HDL-C, mg/dL

Rela

tive C

HD

Ris

k

<130 130-159 ≥160

≥190

160-189 <160

The Framingham Study

Why we Treat Non–HDL-C ? Non-HDL-C is much better (no unique advantages of LDL-C)

but we are stuck with LDL-C for now!

TG 120 mg/dL 400 mg/dL VLDL-C 24 mg/dL 88 mg/dL LDL-C 145 mg/dL 89 mg/dL HDL-C 40 mg/dL 32 mg/dL Non–HDL-C 169 mg/dL 177 mg/dL TG/HDL-C ratio 3.0 12.5

TC 209 mg/dL 209 mg/dL

Ch

ole

ste

rol

(mg

/dL

) Case 1 Case 2

50

100

150

200

225

TC = 209 mg/dL

HDL HDL

LDL

LDL

VLDL

VLDL

Non–HDL-C Stronger CVD.RF. Valid in H.TG Valid non-fasting

<147

>147

<116 >116 <142 >142

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Re

lati

ve

Ris

k o

f C

AD

Small, Dense LDL May Predict CAD

Better than LDL-C, Apo B, and TG

St-Pierre AC, et al. Circulation. 2001;104:2295-2299.

LDL-C (mg/dL)

Apolipoprotein B (mg/dL)

Triglycerides (mg/dL)

39.6%

<39.6%

Small, dense

LDL (<255 Å)

4.0

p<0.001

(N=35)

1.0 (N=35)

6.5

p<0.001

(N=50)

6.5

p=0.13

(N=15)

3.9

p<0.001

(N=27)

1.0 (N=9)

5.9

p<0.001

(N=58)

2.0

p=0.12

(N=14) 1.0

(N=12)

3.3

p<0.001

(N=20) 1.9

p=0.15

(N=11)

5.6

p<0.001

(N=65)

>147 LDL-C

130 mg/dL

LDL-C

130 mg/dL

Elevated Triglycerides Increase the Risk of CHD at All Levels of HDL-C

17.2

4.36.7

7.9

6.1

3.1 3.71.15.7

2.2 1.3 1.0

0

4

8

12

16

20

Od

ds R

ati

o f

or

Pre

matu

re C

AD

<30 30-39 40-49 50+

<200

200-299

>300

HDL-C, mg/dL

Triglycerides,

mg/dL

Hopkins PN, et al. J Am Coll Cardiol. 2005;45:1003-1012.

Agenda







Standards of Medical Care in Diabetes—2013 Dyslipidemia/Lipid Management (1)

Screening

• Most: measure fasting lipid. / y. (B)

• low-risk lipid values: (LDLc <100 , HDLc >50 , and TG <150) (mg/dL)

measure fasting lipid. / 2 y. (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.


Treatment recommendations

lifestyle modification (A)

– Reduction of saturated fat, trans fat, cholesterol intake.

– Increased n-3 fatty acids, viscous fiber, plant stanols/sterols.

– Reduction of Weight. (if indicated)

– Increased physical activity.



Treatment recommendations Statin therapy

• should + lifestyle .

(( regardless of baseline lipid levels)).

– with overt CVD. (A) – without CVD > 40 y. + 1 or >1 other CVD. RF. (A)

• Consider + lifestyle.

– with lower risk (e.g., without overt CVD, < 40 years of age). (C) * LDLc remains >100 mg/dL. * Multiple CVD. RF.



Treatment recommendations

• Combination therapy has been shown not to provide additional cardiovascular benefit above statin therapy alone and is not generally recommended (A)

• Statin therapy is contraindicated in pregnancy (B)



Treatment (LDLc cholesterol) goals

• without overt CVD

– < 100 mg/dL (2.6 mmol/L) (B)

• with overt CVD

– < 70 mg/dL (1.8 mmol/L), (using a high dose of a statin, is an option ) (B)


If targets not reached on maximal tolerated statin therapy Alternative goal: reduce

LDLc ~30–40% from baseline (B)

TG < 150 mg/dL (1.7 mmol/L),

HDLc > 40 mg/dL (1.0 mmol/L) in men and

> 50 mg/dL (1.3 mmol/L) in women, are desirable (C)

ADA/ACC 2008 Consensus Statement: Goals

Brunzell JD, et al. Diabetes Care. 2008;31:811-822.

Whenever TG > 200 mg/dL

LDL-C

Non–HDL-C = Total C – HDL-C

Apo B

Highest-Risk Patients

• Known CVD

• Diabetes plus ≥1 additional major

CVD risk factora

<70 mg/dL <100 mg/dL <80 mg/dL

High-Risk Patients

• No diabetes or known CVD but

≥2 major CVD risk factorsa

• Diabetes but no other major

CVD risk factorsa

<100 mg/dL <130 mg/dL <90 mg/dL

““Very High” 1ry Objective: TG reduction

• TG ≥500 mg/dL 2nd Objective: LDL-C and non–HDL-C reduction

Recommendations for lipid analysis as

treatment target in the prevention of CVD

Every 40

mg/dL

reduction in

LDL-C is

associated

with

corresponding

22%

reduction in

CVD

mortality and

morbidity

LDL-C

remains the

primary

target of

therapy

ESC - 2011

Mechanisms of action of lipid-lowering drugs

CETP Inhibitors

FDA approved supplement

Omega 3 Fish oil

LDL size

Pharmacological

Agents LDL HDL TG other

First-line agents Statins (HMG CoA Reductase Inhibtors)

21 -55%

2 -10%

6 - 30%

Fibrates (PPAR- γ Activators)

20 -25%

6 -18%

20 -35%

Fenofibrate

↓ fibrinogen

↑ LDL size

Second-line agents BAR (Bile Acid Sequestering Resins)

15-25%

Colesevela

m ↓ H A1c

(~0.5%)

Niacin (Plain or SR) 10 -25%

10 -35%

20 -30%

↓Lipoprotein (a)

↑ LDL size

Cholesterol absorption inhibitors 10-18%

11-16% ↓ Apo B &

LDL numb.

ADA. Diabetes Care 2003;26 (suppl 1):S 83-S 86

Take home message.

THANK YOU

Date post:	10-Aug-2015
Category:	Health & Medicine
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