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DYSLIPIDEMIAS: TYPES I-V

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diabetic dyslipidemia frequently characterized by triglycerides, hdl and small, dense ldl. rx of diabetic dyslipidemia may reduce risk of chd. – PowerPoint PPT presentation

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Title: DYSLIPIDEMIAS: TYPES I-V


1
DYSLIPIDEMIAS TYPES I-V
  • Thomas F. Whayne, Jr, MD, PhD, FACC
  • Professor of Medicine (Cardiology)
  • University of Kentucky
  • March 2011.
  • E-Mail twhayn0_at_uky.edu.
  • No conflicts to declare.

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THE MAJOR LIPOPROTEINS
  • CHYLOMICRONS.
  • VERY LOW DENS. LIPOPROT. (VLDL).
  • LOW DENS. LIPOPROT. (LDL) .
  • HIGH DENS. LIPOPROT. (HDL) .






4
Type I
Type IIA
Type IIB
Type III
Type IV
Type V
Normal
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Before UC
After UC
VLDL
Tube Plain
LDL
HDL
8
VLDL
Tube with KB
LDL
HDL
9
TYPE I
  • RARE GENETIC DISORDER.
  • HYPERCHYLOMICRONEMIA.
  • LIPOPROTEIN LIPASE DEFICIENCY.

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TYPE I TREATMENT
  • RESTRICTION OF FATS.
  • PANCREATITIS NPO.
  • MEDIUM CHAIN FATTY ACID TRIGLYCERIDES.

13
TYPE II-A HYPERLIPOPROTEINEMIA
  • AUTOSOMAL DOMINANT.
  • HETEROZYGOTES 1 IN 500.
  • HOMOZYGOTES 1 IN 1,000,000.

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TYPE II-A IS ALSO
  • POLYGENIC.
  • SPORADIC.
  • POSSIBLY ACQUIRED

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TYPE II-A
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY CORONARY.
  • TENDON XANTHOMAS.
  • TUBEROUS XANTHOMAS.
  • XANTHELASMA.
  • CORNEAL ARCUS.

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EXTREME EXAMPLE OF TYPE II-A HYPERLIPOPROTEINEMIA
  • STORMY JONES AGE 10.

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TYPE II-B
  • ACCELERATED ATHEROSCLEROSIS CORONARY AND
    PERIPHERAL

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TYPES IIA/IIB TREATMENT
  • STATINS ESPECIALLY.
  • BILE ACID BINDING RESINS, ESPECIALLY COLESEVELAM.
  • NICOTINIC ACID (NIASPAN).
  • ZETIA.
  • POLICOSANOL.
  • LDL APHERESIS.

24
TYPE III
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY
    PERIPHERAL.
  • PALMAR XANTHOMAS.
  • TUBEROUS XANTHOMAS.

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TYPE III
  • APO E IN LIVER RECEPTORS IS ABNORMAL OR
    DEFICIENT FOR
  • LOW DENS. LIPOPROTEINS (LDL).
  • INTERMED. DENS. LIPOPROTEINS (IDL).
  • CHYLOMICRON REMNANTS.

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TYPE III TREATMENT
  • LOW CHOLESTEROL UNSATURATED FAT DIET.
  • SOME CARBOHYDRATE (SIMPLE SUGARS) RESTRICTION.
  • CLOFIBRATE (ATROMID).
  • GEMFIBROZIL (LOPID).
  • FENOFIBRATE (TRICOR).
  • STATIN.

29
TYPE IV HYPERLIPOPROTEINEMIA
  • ALSO CALLED FAMILIAL HYPERTRIGLYCERIDEMIA.
  • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY
    PERIPHERAL.

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TYPE IV TREATMENT
  • FENOFIBRATE.
  • NICOTINIC ACID (NIASPAN).
  • OMEGA FATTY ACIDS (LOVAZA).
  • METFORMIN.
  • PIOGLITAZONE.
  • STATINS.
  • EZETIMIBE.
  • INSULIN.

32
TYPE V
  • INCREASED CHYLOMICRONS AND VLDL.
  • CAN BE RARE GENETIC DISORDER.
  • CAN BE MORE FREQUENTLY SEEN IN DIABETES, EVEN
    WITH MILD INCREASE IN PLASMA GLUCOSE.

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TYPE V TREATMENT
  • CONTROL DIABETES.
  • FENOFIBRATE.
  • NICOTINIC ACID (NIASPAN).
  • OMEGA FATTY ACIDS (LOVAZA).
  • METFORMIN.
  • PIOGLITAZONE.
  • INSULIN.

36
DYSLILPIDEMIA IN DIABETES TYPICAL PATTERN
  • HIGH LEVELS OF TRIGLYCERIDES.
  • LOW LEVELS OF HDL.
  • PREPONDERANCE OF SMALL DENSE LDL.

37
SMALL, DENSE LDL
  • ASSOCIATED WITH 3X ? RISK OF CHD.
  • INCREASED ATHEROGENICITY
  • FASTER ENTRY INTO BLD. VESSEL WALL.
  • ? BINDING TO LDL RECEPTOR.
  • INCREASED SUSCEPTIBILITY TO OXIDATION.

38
TRIGLYCERIDES IN DIABETES
  • HIGH TRIGLYCERIDE LEVELS OCCUR MAINLY IN VLDL BUT
    ALSO IN CHYLOMICRONS.
  • ELEVATED TRIGLYCERIDE LEVELS RESULT FROM
  • OVERPRODUCTION OF VLDL.
  • IMPAIRED LIPOLYSIS OF TRIGLYCERIDES (INSULIN IS
    AN LPL COFACTOR).

39
ADA RATIONALE FOR Rx OF DYSLIPIDEMIA IN DIABETES
  • THERE IS ? RISK OF CHD BECAUSE OF DYSLIPIDEMIA.
  • DIABETIC DYSLIPIDEMIA FREQUENTLY CHARACTERIZED BY
    ? TRIGLYCERIDES, ? HDL AND ? SMALL, DENSE LDL.
  • Rx OF DIABETIC DYSLIPIDEMIA MAY REDUCE RISK OF
    CHD.

40
IMPROVED CONTROL OF HYPERGLYCEMIA
  • CAN REDUCE DYSLIPIDEMIA.
  • MAY RESULT IN ? ATHEROGENIC DENSE LDL.
  • COMPLETE REVERSAL OF DYSLIPIDEMIA USUALLY NOT
    ACHIEVABLE.

41
RESPONSE OF DENSE LDL TO MEDICATION
  • FIBRATES AND NICOTINIC ACID (NIASPAN) SHIFT
    THESE DENSE LDL TO A LARGER SIZE LDL PARTICLE.
  • STATINS ARE NOT EFFECTIVE IN FAVORABLE SHIFT OF
    DENSE LDL TO LARGER, LESS DENSE LDL PARTICLE.

42
FIBRATES IN TYPE II DIABETICS
STUDY DRUG DIABETIC SUBJECTS RESULTS DIABETES
HELSINKI HEART GEMFI-BROZIL 135 (4081) 65 ? CARDIAC EVENTS, NS
VA HIT GEMFI-BROZIL 627 (2531) 24 ? CAD DEATHS, MI AND CVA, lt 0.05
DAIS FENOFI-BRATE 418(418) 23 ? CV EVENTS, DEATHS (PRELIM.)
43
Syndrome X, Metabolic Syndrome or
Cardiovascular Dysmetabolic Syndrome
  • Obesity.
  • Hypertriglyceridemia.
  • Low HDL.
  • Increased Dense LDL.
  • Hypertension.
  • Insulin Resistance.
  • Hyperuricemia.
  • Increased PAI-1.

44

METABOLIC SYNDROME, SYNDROME X or CV
DYSMETABOLIC SYNDROME
  • AT LEAST 3 OF THE FOLLOWING 5 PRESENT
  • TG ? 150 mg/dl.
  • HDL lt 40 mg/dl in men and lt 50 mg/dl in women .
  • BP ? 130/85 mm/Hg.
  • Waist girth gt 102 cm (men) and gt 88 cm (women).
  • Fasting glucose ? 100 mg/dl.
  • OTHER COMPONENTS
  • ? dense LDL, Insulin resistance, Hyperuricemia,
    ? PAI-1, ? hsCRP, ? Tissue necrosis
    factor-a ? Interleukin-6, ? Resistin,
    and ? Adiponectin.

Grundy SM, et al. Circulation 20051122735-2752.
45
Metabolic Syndrome Prevalence Increases with Age
47 million or 23 of US adults have the metabolic
syndrome
Adapted from Ford ES, et al. JAMA
2002287356-359.
46
MARKED HYPERTRIGLYCERIDEMIA CAN OCCUR FROM
RETROVIRUS Rx IN HIV PATIENTS

47
Thiazides
  • Marked elevation of triglycerides and VLDL can
    occur.
  • Increased total cholesterol and LDL.
  • Little effect on HDL.

48
ESTROGEN
  • SPORADICALLY AND UNPREDICTABLY, ESTROGEN MAY
    CAUSE A MARKED ELEVATION IN TRIGLYCERIDES.

49
BETA BLOCKERS
  • Increase triglycerides and VLDL.
  • Decrease HDL.
  • Less significant increase in Total Cholesterol
    and LDL.
  • Beta Blockers with ISA may have a less pronounced
    effect.

50
CONCLUSION
  • MULTIPLE APPROACHES AVAILABLE TO ACHIEVE GOOD
    BLOOD LIPID CONTROL AND THEREBY AVOID MULTIPLE
    CLINICAL PROBLEMS INCLUDING SEQUELAE OF CORONARY
    ATHEROSCLEROSIS.
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