Diabetic Dyslipidemia- Dr Shahjada Selim

Dr Shahjada Selim
Associate Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University
Email: selimshahjada@gmail.com, info@shahjadaselim.com

The lipid abnormalities associated with
insulin resistance affect all lipid fractions.
They are characterised by elevated fasting
triglyceride levels, elevated postprandial
triglyceride-rich remnant lipoproteins, low
HDL cholesterol, and small dense LDL
particles. This pattern correlates strongly
with cardiovascular risk, and treatment
decreases this risk.
Diabetic Dyslipidemia

Apolipoprotein B (apo B) is typically
associated with LDL cholesterol; however,
in insulin resistant atherogenic dyslipidemia,
in response to increased delivery of free
fatty acids to the liver, there is an
overproduction of apo B and increased
VLDL triglyceride synthesis.

This includes VLDL particles which contain apo B.
Low HDL cholesterol levels are an independent risk
factor for cardiovascular disease; the low HDL seen
in atherogenic dyslipidemia relates to a reduced
HDL particle size.
The low HDL particle size relates to exchange of
VLDL triglycerides for cholesterol esters in LDL and
HDL via cholesterol ester transfer protein. When the
triglycerides in LDL and HDL undergo hydrolysis,
small, cholesterol depleted LDL and HDL remain.

Small dense LDL particles are reported to
be more atherogenic possibly because of
their increased propensity to oxidation and
greater proportion of apo B. Compared with
non-insulin resistant states, a given LDL
cholesterol level represents a greater
number of apo B containing small dense
LDL particles and this confers increased
risk.

 Lifestyle modification focusing on weight loss (if
indicated); application of a Mediterranean style or
Dietary Approaches to Stop Hypertension (DASH)
eating pattern; reduction of saturated fat and trans
fat; increase of dietary n-3 fatty acids, viscous fiber,
and plant stanols/sterols intake;
 Increased physical activity should be recommended
to improve the lipid profile and reduce the risk of
developing atherosclerotic cardiovascular disease in
patients with diabetes.
Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S111-S134

 Intensify lifestyle therapy and optimize glycemic
control for patients with elevated triglyceride
levels (≥150 mg/dL [1.7mmol/L]) and/or low HDL
cholesterol (<40 mg/dL [1.0 mmol/L] for men,
<50 mg/dL [1.3 mmol/L] for women).
Cardiovascular Disease and Risk Management:
Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl. 1):S111-S134

• This is the equivalent of doubling the
daily dose of a statin
• Therefore, successful dietary therapy
reduces drug therapy by over 50%
• Dietary therapy reduces LDL cholesterol
by 7-10%

Dietary Therapy for Elevated Blood Cholesterol
 30% of total calories
 55% of total calories
~ 15% of total calories
To achieve and maintain
desirable weight
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015-3023.
Nutrient*
* Calories from alcohol not included.
<10% of
total calories
< 300 mg/day
Total fat
Saturated fatty acids
Carbohydrates
Protein
Cholesterol
Total calories
< 7% of
total calories
< 200 mg/day
Recommended intake
Step I Diet Step II Diet

Side Effects of HMG CoA
Reductase Inhibitors
• Myopathy (0.1%)
• Abnormal Liver Function Tests (1-2%)
• Gastrointestinal Distress and Diarrhea
• CNS – Insomnia
• Diabetes

• Liver Disease
• Multisystem Disease
• Drugs:
- Cyclosporin; tacrolimus
- Fibrates
- Erythromycin
- Itraconazole, ketoconazole
- Mibefradil (Posicor)
- ? Protease inhibitors
Precipitating Factors:

Check CK
prior to initiating statin therapy

Antibiotics clarithromycin* erythromycin* metronidazole
Antifungals ketoconazole* itraconazole** miconazole
Protease Inhibitors indinivir ritonavir nelfinivir
CCB’s mibefradil**
Immunosuppressant cyclosporin A*
H2 Blockers cimetidine
Antidepressants fluoxetine fluvoxamine
Food grapefruit grapefruit juice

 Hypocaloric, low fat (10-20%), alcohol restricted
diet. Avoid saturates, simple Carbs. Exercise and
weight loss.
 In DM: Optimize glycemic control
 Consider metformin or thiazolidenedione for
IGT/insulin resistance
 Assess meds: oral estrogens/OCPs, steroids,
Retin A, thiazides or B blockers
 Drugs: 1 : Fibrates or Niacin (unless DM)
2 : High dose statins, Fish Oils

Hypertriglyceridemia
Drug Therapy: High Risk Patients
Triglycerides
Treat to prevent/
reverse ASCVD
Treat to prevent
pancreatitis
<800 mg/dl > 1,000 mg/dl
R/O
Secondary Hyperlipidemia
Diet/Lifestyle Modification

TG  200 TG 200-400 TG 400
Statin Statin Combined
DrugTherapy
Useful Combinations:
Hypercholesterolemia:
Mixed HLD:
Statins+Resins/Ezitamibe
Statins/Ezit+Niacin, or
Statins/Ezit+ Fibrates*
Resin Niacin Consider High
Niacin Gemfibrozil DoseStatins

• Triglycerides 150 -1000. Treat to prevent CAD*
• Triglycerides > 1000. Treat to prevent
pancreatitis
* If in doubt measure Apo B 100.
Median 100 mg/dl; > 125 mg/dl likely atherogenic

 Primary target of therapy: identification of LDL-C;
goal for persons with diabetes: <100 mg/dL
 Therapeutic options:
 LDL-C 100–129 mg/dL: increase intensity ofTLC; add
drug to modify atherogenic dyslipidemia (fibrate or
nicotinic acid); intensify risk factor control
 LDL-C 130 mg/dL: simultaneously initiateTLC and
LDL-C–lowering drugs
 TG 200 mg/dL: non–HDL-C* becomes secondary
target
JAMA. 2001;285:2486-2497.
Note: Diabetic dyslipidemia is essentially atherogenic dyslipidemia in persons with type 2
diabetes.
*Non–HDL-C goal is set at 30 mg/dL higher than LDL-C goal.

Fibric Acid Derivatives
• Gemfibrozil (Lopid) 600-1200 mg/day
Clofibrate (Atromid S) 1000-2000 mg/day
Fenofibrate (Tricor) 54-160 ug/ day
• Mechanism: Increases clearance of
triglyceride-rich lipoproteins (Chylos, VLDL,
remnants) through downregulation of Apo CIII
and increased LPL activity
• Effects on Lipids:
TG 20-50 %
HDL-C 10-15 %
LDL-C variable

Fibric Acid Derivatives -
Indications
• Severe Hypertriglyceridemia (TG > 1000 mg/dl)
• ? Combination therapy for mixed hyperlipidemia or
moderate hypertriglyceridemia
• Reduces risk of CHD in subjects with High TG
/Low HDL-C
• May raise homocysteine levels

Fibric Acid Derivatives
• Side Effects
Myopathy
Hepatitis (increases in transaminases)
Gallstones, Nausea, Diarrhea
•Contraindications
Absolute: Relative:
Gallstones Use with statins
Hepatic Insufficiency Inhibitors of CYP 3A4
Pregnancy

 In adults not taking statins or other lipid-lowering
therapy, it is reasonable to obtain a lipid profile at
the time of diabetes diagnosis, at an initial medical
evaluation, and every 5 years thereafter if under
the age of 40 years, or more frequently if
indicated.

 Obtain a lipid profile at initiation of statins or other
lipid-lowering therapy, 4–12 weeks after initiation
or a change in dose, and annually thereafter as it
may help to monitor the response to therapy and
inform medication adherence.

For patients with diabetes aged 40–75 years
without atherosclerotic cardiovascular disease,
use moderate-intensity statin therapy in addition
to lifestyle therapy.
For patients with diabetes aged 20–39 years with
additional atherosclerotic cardiovascular disease
risk factors, it maybe reasonable to initiate statin
therapy in addition to lifestyle therapy.

In patients with diabetes at higher risk, especially
those with multiple atherosclerotic cardiovascular
disease risk factors or aged 50–70 years, it is
reasonable to use high-intensity statin therapy.
In adults with diabetes and 10-year ASCVD risk of
20% or higher, it may be reasonable to add
ezetimibe to maximally tolerated statin therapy to
reduce LDL cholesterol levels by 50% or more.

 For patients of all ages with diabetes and
ASCVD, high-intensity statin therapy should
be added to lifestyle therapy.
 For patients with diabetes and ASCVD
considered very high risk using specific
criteria, if LDL cholesterol is ≥70 mg/dL on
maximally tolerated statin dose, consider
adding additional LDL-lowering therapy (such
as ezetimibe or PCSK9 inhibitor).
Ezetimibe may be preferred due to lower cost.

 For patients who do not tolerate the intended
intensity, the maximally tolerated statin dose
should be used.
 In adults with diabetes aged >75 years already
on statin therapy, it is reasonable to
continue statin treatment.

In adults with diabetes aged >75 years, it may
be reasonable to initiate statin therapy after
discussion of potential benefits and risks.
Statin therapy is contraindicated in pregnancy.

For patients with fasting triglyceride levels ≥500 mg/dL,
evaluate for secondary causes of
hypertriglyceridemia and consider medical therapy to
reduce the risk of pancreatitis.
In adults with moderate hypertriglyceridemia (fasting or
non-fasting triglycerides 175–499 mg/dL),
clinicians should address and treat lifestyle factors
(obesity and metabolic syndrome), secondary factors
(diabetes, chronic liver or kidney disease and/or
nephrotic syndrome, hypothyroidism), and
medications that raise triglycerides.

In patients with atherosclerotic cardiovascular
disease or other cardiovascular risk factors on a
statin with controlled LDL cholesterol but
elevated triglycerides (135–499 mg/dL), the
addition of icosapent ethyl can be considered
to reduce cardiovascular risk.

 Statin plus fibrate combination therapy has not
been shown to improve atherosclerotic
cardiovascular disease outcomes and is
generally not recommended.
 Statin plus niacin combination therapy has not
been shown to provide additional
cardiovascular benefit above statin therapy
alone, may increase the risk of stroke with
additional side effects, and is generally not
recommended.

Diabetic Dyslipidemia- Dr Shahjada Selim

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