Diabetic Dyslipidaemia

BY

بسم هللا الرحمن الرحيم

KHALED EL SAYED EL HADIDY. MD

Head of Internal Medicine Department.

Head of Diabetes and Endocrinology Unit.

Beni-Suef University.

• Apo A-1

• SD LDL

HDL

Apo A-1

(CETP)

(LACT)

Proteolysis of Apo B-100

Clearance LPL, APO CIII

TG

Apo B

IR-----FFA

SD

LDL

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

(CETP)

Apo A-1

(CETP)

( 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.

CAD. Risk Factors.

four groups of individuals were identified for whom an

extensive body of RCT evidence demonstrated a reduction in

atherosclerotic cardiovascular disease (ASCVD) events

with a good margin of safety from statin therapy:

No LDL-C or non-HDL-C treatment targets

Four Statin Benefit Groups:

• Individuals with clinical ASCVD (acute coronary syndromes, or a history of MI, stable or unstable angina,coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin ) without New York Heart Association (NYHA) class II-IV heart failure or receiving hemodialysis.

• Individuals with primary elevations of LDL-C ≥ 190 mg/dl.

• Individuals 40-75 years of age with diabetes, and LDL-C 70-189 mg/dl without clinical ASCVD.

• Individuals without clinical ASCVD or diabetes, who are 40-75 years of age with LDL-C 70-189 mg/dl, and have an estimated 10-year ASCVD risk of 7.5% or higher.

Pooled Cohort Equations for (ASCVD) risk assessment

Patient is at High-Risk of ASCVD

Implement treatment recommendations:

• A – Aspirin / Antiplatelet therapy• B – Blood pressure control• C – Cholesterol control /Cigarette smoking cessation• D – Diet and weight management / Diabetes and blood

sugar control• E – Exercise

Standards of Medical Care in Diabetes—2015Dyslipidemia/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 2014;37(suppl 1):S38

Standards of Medical Care in Diabetes—2015Dyslipidemia/Lipid Management (2)

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.

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S38

Standards of Medical Care in Diabetes—2015Dyslipidemia/Lipid Management (3)

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.

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S38

Standards of Medical Care in Diabetes—2015Dyslipidemia/Lipid Management (4)

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)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S38

Standards of Medical Care in Diabetes—2015Dyslipidemia/Lipid Management (2015)

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)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S38

If targets not reached on maximal tolerated statin therapyAlternative 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)

However, LDL cholesterol–targeted statin therapy remains the preferred strategy (A)

• Intensify lifestyle and optimize glycemic control for patients with C

– Triglyceride >150 mg/dL.

– HDL cholesterol >40 mg/dL in men and >50 mg/dL in women

• For fasting triglyceride > 500 mg/dL , evaluate for secondary causes and consider medical therapy to reduce the risk of pancreatitis C

• In clinical practice, providers may need to adjust intensity of statin therapy based on individual patient response to medication (e.g. side effects, tolerability, LDL cholesterol levels.) E

• Cholesterol laboratory testing may be helpful in monitoring adherence to therapy but may not be needed once the patient is stable on therapy E

• 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

Recommendations: Dyslipidemia/Lipid Management

Primary Objectives of Effective Management

A

B

C

45 50 55 60 65 70 75 80 85 90

9

8

7

130

100

145

140

Patient Age

Reduction of both micro- and macro-vascular event rates …by 75%

lGæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2

diabetes. N Engl J Med. 2003;348:383-393.

Mechanisms of action of lipid-lowering drugs

CETP Inhibitors

FDA approved supplement

Omega 3 Fish oil

LDL size

Pharmacological

AgentsLDL HDL TG other

First-line agentsStatins (HMG CoA Reductase Inhibtors)

21 -55%

2 -10%

6 - 30%

Fibrates (PPAR- γActivators)

20 -25%

6 -18%

20 -35%

Fenofibrate

↓ fibrinogen

↑ LDL size

Second-line agentsBAR (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.