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The Volcano

The Volcano. Diabetes and Cardio Metabolic Risk. Dr. R. V. S. N. Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist. www.drsarma.in. Heaven and Hell. Sutton-Osler- Rendu -Weber-Syndrome (HHT) Tsutsugamushi fever Criggler Najar Syndrome

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The Volcano

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  1. The Volcano www.drsarma.in

  2. Diabetes and Cardio Metabolic Risk Dr. R. V. S. N. Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist www.drsarma.in

  3. Heaven and Hell Sutton-Osler-Rendu-Weber-Syndrome (HHT) Tsutsugamushi fever Criggler Najar Syndrome Diabetes Mellitus – Diagnosis Prevention, Complications and Modern Management www.drsarma.in

  4. Our Greatness You see ! • Saarejehan se achchaa …….Hindustan hamara… • Saarejehan se oonchaa …….T2DM hamarahamara… • Saarejehan se oonchaa …….CADI hamarahamara… • 2 to 6 fold higher CAD than people of other ethnicity • Indians have the highest among the highest CAD rates • Irrespective of gender, region, religion, SES • Same is true of immigrant Indians all over the globe • CAD risk is considerable even in vegetarian Indians • Indian CAD is 10 years younger, Often silent MI • TVD, DVD, SD, MACE are more in Indians www.drsarma.in

  5. Today’s Thinking METABOLOGIST IS BORN !! DIABETOLOGIST IS DEAD !! The Islet, Vol 3, No2, May 2005 www.drsarma.in

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

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  13. “Genetics loads the gun, environment pulls the trigger. Even when you have a loaded gun, if you don’t pull the trigger, no harm is done." Dr. Enas A Enas Director, CADI Research Foundation www.drsarma.in

  14. Micro and Macrovascular Onslaught www.drsarma.in

  15. Ticking Clock of T2DM • Micro-vascular (DR, CKD, 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) VP • 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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  17. 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

  18. 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

  19. 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

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

  21. DM – Strongest RF for CVD DM = CAD www.drsarma.in

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

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

  30. 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

  31. Two Sides of the Coin Type 2 Diabetes Coronary Artery Disease www.drsarma.in

  32. Atherogenic Particles Non-HDL-C Measurements Apolipoprotein B VLDL VLDLR IDL LDL SDL TG rich particles Cholesterol rich www.drsarma.in 32

  33. 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

  34. 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 • Lipemia Retinalis LDL Level of 180 to 220 mg www.drsarma.in

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

  36. Small Dense LDL and CHD Potential Atherogenic Mechanisms • Increased susceptibility to oxidation • Increased vascular permeability • Increased binding to arterial wall proteoglycons • 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

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  40. Multiplicative Effect www.drsarma.in

  41. 2004 Vascular Protection in Diabetes Mellitus www.drsarma.in

  42. Glycemic control alone is hopelessly inadequate !! The A B C of Diabetes Management A A1c (Hb A1c) B Blood pressure (goal) C Cholesterol (all lipids) www.drsarma.in

  43. How to offer Vascular Protection ? ACE inhibitors or ARBs ASA (Acetyl Salicylic Acid) Atorvastatin (Lipid management) A1c control (Glycemic control) Blood pressure goal (<130/80) Control of Nephropathy, Proteinuria (MAU) Cigarette smoking cessation Weight and waist management Physical Activity – at least 2 km/d x 5 d www.drsarma.in

  44. Goals inT2DM for VP ADA, CDA, IDF, WWD www.drsarma.in

  45. From Blood Sugar to Blood Vessel www.drsarma.in

  46. ACEi in T2DM - VP • Antihypertensive, vasoprotective, anti-thrombotic, and anti-inflammatory properties – Inevitable in DM • Reduce CV events, Reduce atherosclerosis • Reduce renal disease which is a strong CV risk factor • Metabolically ‘friendly’ drugs that prevent rises in glucose & prevent diabetes • Well-tolerated with few side effects www.drsarma.in

  47. MNT and Dyslipidemia • Total CHO to be reduced < 50% of calories • Saturated fat must reduced to< 7% of calories • MUFA and PUFA up to 15% of calories • Protein in take to be increased – 25% of cal. • Dietary fiber > 20 g/day -Soy protein, Fenugreek • Vegetables, Nuts and fruits must every day • Fish oils – Omega-3 fatty acids www.drsarma.in

  48. Priorities for Treatment • Lifestyle interventions (TLC) MNT, Physical Activity, Weight and Waist reduction • Statin in a minimum dose of 10 mg o.d • Follow up every one year by full lipid profile • All Indians must be tested for LP(a) and If > 30 mg% - Niacin SR 350 to 500 mg started www.drsarma.in

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  50. Paradigm Shift in T2DM Diabetes as of now • Cardiometabolic disease • Hb A1c, FBG, PPBG • Insulin Resistance, ID • Metformin, Glitazones • Beta cell preservation • Early Insulin use • Prevention; Intense Rx. • Pre DM (IFG, IGT), DM • Blood vessel; guardian Rx. • DM = CAD; Prevention • MAU, Micro, Macro com. About 10 to 15 years ago • Only Dysglycemia • Urine, RBG, GTT • Insulin deficiency • Secretagogues – SU •  cell stimulation • Insulin as a last resort • Treatment of DM only • BG > 180, No IFG, IGT • Blood Sugar Disease • DM is a mild disease • Emphasis on complic. less www.drsarma.in

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