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Diabetic Dyslipidemia

Diabetic Dyslipidemia. Dr. R. V. S. N. Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist. www.drsarma.in. What types of lesions cause MI ?. Coronary stenosis severity prior to MI. 100. 100. 14%. 80. 80. 18%. 60. 60. 68%. Coronary stenosis (%). 40. 40. 20.

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Diabetic Dyslipidemia

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  1. Diabetic Dyslipidemia Dr. R. V. S. N. Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist www.drsarma.in

  2. www.drsarma.in

  3. www.drsarma.in

  4. What types of lesions cause MI ? Coronary stenosis severity prior to MI 100 100 14% 80 80 18% 60 60 68% Coronary stenosis (%) 40 40 20 20 0 0 Ambrose1988 Little1988 Nobuyoshi1991 Giroud1992 All fourstudies <50% 50%-70% >70% Falk E, et al. Circulation. 1995;92:657-671. www.drsarma.in

  5. What types of lesions cause MI ? Coronary stenosis severity prior to MI 100 100 14% 80 80 18% 60 60 68% Not the degree of stenosis Coronary stenosis (%) 40 40 20 20 0 0 Ambrose1988 Little1988 Nobuyoshi1991 Giroud1992 All fourstudies <50% 50%-70% >70% Falk E, et al. Circulation. 1995;92:657-671. www.drsarma.in

  6. CV Risk Factors in Diabetes 12 10.0 10 8 6.5 Odds Ratio 6 3.2 4 2.3 2 0 Microalbuminuria Smoking Diastolic BP Cholesterol Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32. www.drsarma.in

  7. Causes of death in Diabetes www.drsarma.in

  8. Diabetes = Coronary A D Why is it so ? www.drsarma.in

  9. DM – Strongest RF for CVD DM = CHD www.drsarma.in

  10. Duration of T2DM and CVD 48% 29% 24% 21% 15% ≤ 2 3-5 6-9 10-14 15+ Years after DM Diagnosis Harris, S et al.; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load. CDA 2003. www.drsarma.in

  11. Duration of DM - CV Mortality 4 p for trend <0.001 3.5 3 2.5 Relative Risk 2 1.5 1 0.5 0 < 5 6 to 10 11 to 15 16 to 25 26 + Duration of Diabetes (years) Cho, et al. J Am Coll Card 2002:40:954. www.drsarma.in

  12. Life Expectancy with Diabetes Years DM 90 No DM 1600 80 1400 70 1200 60 Diabetes 1000 No Diabetes 50 800 40 600 30 400 20 200 10 0 0 Mortality rate/100,000 Men Women Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003. www.drsarma.in

  13. Cardiovascular Disease and T2DM 20% Diabetes 15% No Diabetes Prevalence of CV Disease 10% 5% 0% Hypertension Heart Disease Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003. www.drsarma.in

  14. Clinical Outcome for Diabetes 4-year Follow-up 14 12 10 8 % 6 4 2 0 CV Death MI Stroke Dialysis HOPE / MICRO-HOPE. Lancet 2000;355:253. www.drsarma.in

  15. ACS and Diabetes – Up to 1 Year 25 P<0.0001 No Diabetes 20 21.3 N = 3429 P<0.0001 Diabetes 15 N = 1149 % of patients 14.4 14.1 P=0.035 10 8.9 7.9 P<0.0001 7.1 5 3.9 1.8 0 In-Hospital Non-fatal MI 1-y All-Cause 1-y Mortality Mortality Mortality/MI Yan R,et al.Can J Cardiol 2003;19(suppl A):260A. www.drsarma.in

  16. OASIS Study: Total Mortality 0.25 Diabetes/CVD +, (n = 1148) RR = 2.88 (2.37-3.49) Diabetes/CVD -, (n = 569) 0.20 No Diabetes/CVD +, (n = 3503) No Diabetes/CVD -, (n = 2796) RR=1.99 (1.52-2.60) 0.15 Event rate 0.10 RR=1.71 (1.44-2.04) 0.05 RR=1.00 0.0 Months  3 6 9 12 15 18 21 24 Malmberg K, et al. Circulation 2000;102:1014–1019. www.drsarma.in

  17. Predictors of CV Risk in DM www.drsarma.in

  18. DM = CAD - Because • CVD is responsible for 60 - 75% of mortality in T2DM • CVD is 4 times more prevalent in diabetes; CADI is more • CVD prevalence increases with age, so is T2DM • CVD in DM is often severe, silent, poor prognosis and fatal • Diabetes ↑ mortality, 50% pre adm / recurrent MI and ACS • Diabetes erases the protection conferred to women • At diagnosis of T2DM, most patients have evidence of CVD • Abnormal Glucose tolerance is a strong CV Risk factor www.drsarma.in

  19. The Lipid Profile How to interpret ? www.drsarma.in

  20. HDL A I, A II B 100 TG TG C TG TG C C B 48+E+C CM B 100 + E +C Lipoproteins LDL VLDL www.drsarma.in 20

  21. Atherogenic Particles Non-HDL-C Measurements Apolipoprotein B VLDL VLDLR IDL LDL SDL TG rich particles Cholesterol rich www.drsarma.in 21

  22. The Good, Bad, Ugly and Deadly • Total Cholesterol < 200 • ‘Good’ Cholesterols (HDL) • HDL 1, HDL 2, HDL 3 > 50 • ‘Bad’ Cholesterols (Non HDL) < 150 • LDL, IDL < 100 • VLDL, VLDL-R< 30 • Lp(a), Small LDL < 20 HDL 1 and HDL 2 are protective www.drsarma.in 22

  23. Today’s Safer Values • Total Cholesterol < 200 • Triglycerides < 150 • LDL Cholesterol < 100 preferably < 70 • HDL Cholesterol > 50 (for women 55) • Bad Cholesterols the lower the better • Good Cholesterols the higher the better • Non HDL Cholesterol < 130 • Lp(a) values < 20 www.drsarma.in

  24. Dyslipidemia in Diabetes What are the Mechanisms ? www.drsarma.in

  25. Atherosclerosis and Insulin Resistance Hypertension Obesity Hyperinsulinemia Diabetes Hyper triglyceridemia Small, dense LDL Low HDL Hyper coagulability InsulinResistance Atherosclerosis www.drsarma.in

  26. Insulin Resistance - Clinical Clues • Abdominal obesity • ↑ TG + ↓ HDL-C • Glucose intolerance • Hypertension • Atherosclerosis • Ethnicity (Indians, Negroid races) www.drsarma.in

  27. Dyslipidemia in DM and IRS • Elevated total TG • Reduced HDL • Small, dense LDL • ↑ HDL 3 and ↓ HDL1 and HDL 2 • LDL is not usually high • Postprandial Hyper lipemia LDL Level of 180 to 220 mg www.drsarma.in

  28. Dyslipidemia in DM and IRS Increased Decreased • Triglycerides • VLDL • LDL, sLDL • Apo B • HDL • Apo A-I www.drsarma.in

  29. Dyslipidemia based on TG and LDL www.drsarma.in

  30. Dyslipidemia based on TG and Apo B www.drsarma.in

  31. Mechanisms of DM Dyslipidemia Fat Cells Liver FFA X IR Insulin www.drsarma.in

  32. Mechanisms of DM Dyslipidemia Fat Cells Liver FFA  TG  Apo B  VLDL VLDL X IR Insulin www.drsarma.in

  33. Mechanisms of DM Dyslipidemia Fat Cells Liver FFA CE (hepaticlipase)  TG  Apo B  VLDL (CETP) HDL VLDL X IR TG Apo A-1 Kidney Insulin www.drsarma.in

  34. Mechanisms of DM Dyslipidemia Fat Cells Liver FFA CE (hepaticlipase)  TG  Apo B  VLDL (CETP) HDL VLDL X IR TG Apo A-1 (CETP) CE TG Kidney Insulin SDLDL LDL (lipoprotein or hepatic lipase) www.drsarma.in

  35. 625 500 400 300 200 100 r = 0.73 P < 0.0001 Plasma TG (mg/dL) 100 200 300 400 500 600 IR and TG Increase Insulin Response to Oral Glucose Olefsky JM et al. AmJMed. 1974;57:551-560. www.drsarma.in

  36. DM, IRS and HDL Hyperinsulinemic Normoinsulinemic P < 0.005 P < 0.005 HDL-C (mg/dL) Non-obese Obese Reaven GM. In: Le Roith D et al., eds. Diabetes Mellitus.1996:509-519. www.drsarma.in

  37. Effects of  TG on CV Risk • Accumulation of chylomicron remnants • Accumulation of VLDL remnants • Generation of small, dense LDL • Association with low HDL • Increased coagulability •  PAI-1, and  factor VIIc • Activation of prothrombin to thrombin www.drsarma.in

  38. Small Dense LDL and CHD Potential Atherogenic Mechanisms • Increased susceptibility to oxidation • Increased vascular permeability • Conformational change in Apo B • ↓ Affinity for LDL receptor (↓ clearance) • Association with insulin resistance syndrome • Association with high TG and low HDL Austin MA et al. Curr Opin Lipidol 1996;7:167-171. www.drsarma.in

  39. Research on DM Dyslipidemia What the studies say ? www.drsarma.in

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  44. Multiplicative Effect www.drsarma.in

  45. Clear Excess mortality in DM www.drsarma.in

  46. Vascular Protection in DM A New Paradigm !!! www.drsarma.in

  47. Glycemic control alone is hopelessly inadequate !! www.drsarma.in

  48. The A B C of Diabetes Management A A1c (Hb A1c) B Blood pressure (goal) C Cholesterol (all lipids) www.drsarma.in

  49. Ticking Clock of T2DM • Micro-vascular (DR, DKD, DPN, DAN) • At the onset of hyperglycemia • Control of hyperglycemia essential • The A1c target of less than 7 must (A) • Macro-vascular (CAD, CVD, PVD) • At the onset of insulin resistance • Blood pressure goal of 130/80 (B) • Control of lipid abnormalities (C) www.drsarma.in

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