www drsarma in 1 Diabetes and Cardio Metabolic

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

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 3

Our Greatness You see ! • Saare jehan se achchaa ……. Hindustan hamara… • Saare jehan se oonchaa ……. T 2 DM hamara… • Saare jehan se oonchaa ……. CADI hamara… • 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 www. drsarma. in • Indian CAD is 10 years younger, Often silent MI 4

Today’s Thinking METABOLOGIST IS DIABETOLOGIST IS BORN DEAD !! The Islet, Vol 3, No 2, May 2005 www. drsarma. in 5

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

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“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 13

Micro and Macrovascular Onslaught DPN, DAN PDR, NPDR PAD T 2 DM CKD, Nephro CVD CAD www. drsarma. in 14

Ticking Clock of T 2 DM 1. Micro-vascular (DR, CKD, DPN, DAN) § § § At the onset of hyperglycemia Control of hyperglycemia essential The A 1 c target of less than 7 must (A) 2. Macro-vascular (CAD, CVD, PVD) VP § § § www. drsarma. in At the onset of insulin resistance Blood pressure goal of 130/80 (B) Control of lipid abnormalities (C) 15

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What types of lesions cause MI ? Coronary stenosis (%) Coronary stenosis severity prior to MI 100 80 80 18% 60 60 68% 40 40 20 20 0 0 Ambrose 1988 Little 1988 Nobuyoshi 1991 <50% www. drsarma. in Giroud 1992 50%-70% 14% All four studies >70% Falk E, et al. Circulation. 1995; 92: 657 -671. 17

What types of lesions cause MI ? Coronary stenosis severity prior to MI Coronary stenosis (%) 100 80 f o e e r g e d e h t t o N 60 40 20 0 Ambrose 1988 Little 1988 Nobuyoshi 1991 <50% www. drsarma. in s i s 80 o 18% n e st 60 68% 40 20 0 Giroud 1992 50%-70% 14% All four studies >70% Falk E, et al. Circulation. 1995; 92: 657 -671. 18

CV Risk Factors in Diabetes 12 10. 0 Odds Ratio 10 8 6. 5 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 19

Causes of death in Diabetes www. drsarma. in 20

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

Duration of T 2 DM and CVD 48% 29% 21% 24% 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 22

Duration of DM - CV Mortality 4 p for trend <0. 001 Relative Risk 3. 5 3 2. 5 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 23

Life Expectancy with Diabetes Years 90 80 70 60 50 40 30 20 10 0 DM No DM Men 1600 1400 1200 1000 800 600 400 200 0 Women Diabetes No Diabetes Mortality rate/100, 000 Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003. www. drsarma. in 24

Cardiovascular Disease and T 2 DM Prevalence of CV Disease 20% Diabetes No Diabetes 15% 10% 5% 0% Hypertension Heart Disease Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003. www. drsarma. in 25

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 26

ACS and Diabetes – Up to 1 Year % of patients 25 20 15 0 21. 3 N = 3429 Diabetes P<0. 0001 N = 1149 14. 4 P=0. 035 10 5 P<0. 0001 No Diabetes P<0. 0001 1. 8 3. 9 In-Hospital Mortality 7. 1 8. 9 Non-fatal MI 14. 1 7. 9 1 -y All-Cause Mortality 1 -y Mortality/MI Yan R, et al. Can J Cardiol 2003; 19(suppl A): 260 A. www. drsarma. in 27

OASIS Study: Total Mortality 0. 25 Event rate 0. 20 Diabetes/CVD +, (n = 1148) Diabetes/CVD -, (n = 569) No Diabetes/CVD +, (n = 3503) No Diabetes/CVD -, (n = 2796) RR = 2. 88 (2. 37 -3. 49) 0. 15 RR=1. 99 (1. 52 -2. 60) 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 28

Predictors of CV Risk in DM Age; But Gender looses its power MAU (Microalbuminuria) W/Ht Ratio (Abdominal Obesity) LP(a) (Lipoprotein small ‘a’) LDL Cholesterol Not the Glycemic levels !! www. drsarma. in 29

DM = CAD - Because • • CVD is responsible for 60 - 75% of mortality in T 2 DM CVD is 4 times more prevalent in diabetes; CADI is more CVD prevalence increases with age, so is T 2 DM 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 T 2 DM, most patients have evidence of CVD Abnormal Glucose tolerance is a strong CV Risk factor www. drsarma. in 30

Two Sides of the Coin www. drsarma. in 31

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

Today’s Safer Values ü Total Cholesterol < 200 ü Triglycerides < 150 ü LDL Cholesterol < 100 preferably < 70 ü HDL Cholesterol > 50 (for women 55) ü Bad Cholesterols the lower the better ü Good Cholesterols the higher the better ü Non HDL Cholesterol < 130 www. drsarma. in 33

Dyslipidemia in DM and IRS • • Elevated total TG LDL Level of Reduced HDL 180 to 220 mg Small, dense LDL ↑ HDL 3 and ↓ HDL 1 and HDL 2 LDL is not usually high Postprandial Hyper lipemia Lipemia Retinalis www. drsarma. in 34

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

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 36

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M www. drsarma. in E e v i t a c i l p i t l u e f f t c 40

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

Glycemic control alone is hopelessly inadequate !! The A B C of Diabetes Management A A 1 c (Hb A 1 c) B Blood pressure (goal) C Cholesterol (all lipids) www. drsarma. in 42

How to offer Vascular Protection ? 1. 2. 3. 4. 5. 6. ACE inhibitors or ARBs ASA (Acetyl Salicylic Acid) Atorvastatin (Lipid management) A 1 c control (Glycemic control) Blood pressure goal (<130/80) Control of Nephropathy, Proteinuria (MAU) 7. Cigarette smoking cessation 8. Weight and waist management 9. Physical Activity – at least 2 km/d x 5 d www. drsarma. in 43

Goals in. T 2 DM for VP Risk Factor Goal or Target Glycemia Hb A 1 c < 6. 5% Blood Pressure < 130/80 mm Hg LDL target < 100 mg%; better < 70 HDL target > 40 men, > 50 women TG target < 150 mg% BMI < 25 kg/m 2 Physical activity At least 5 days - 2 km/day ADA, CDA, IDF, WWD www. drsarma. in 44

From Blood Sugar to Blood Vessel ACEi (Ramipril) Vasoprotective, anti HT, ↓ ED ASA (75 to 150 mg%) Anti inflamm. , Anti Platelet Statin (Powerful, full) ↓ LDL, TG, Corrects ED, Inflam BP Goal Vascular damage, LVH, CVA Glycemic control ↓ Micro vascular ? Macrovascular Physical activity ED, ↓ Inflammation, ↑ HDL Diet and TLC ↓ TG, LDL, Glycemia, Weight Smoking cessation ↓ ED and Inflammation www. drsarma. in 45

ACEi in T 2 DM - 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 46

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 47

Priorities for Treatment 1. Lifestyle interventions (TLC) MNT, Physical Activity, Weight and Waist reduction 2. Statin in a minimum dose of 10 mg o. d 3. Follow up every one year by full lipid profile 4. All Indians must be tested for LP(a) and If > 30 mg% - Niacin SR 350 to 500 mg started www. drsarma. in 48

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About 10 to 15 years ago 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Diabetes as of now 1. Cardiometabolic disease 2. Hb A 1 c, FBG, PPBG 3. Insulin Resistance, M ID D 2 Glitazones T 4. Metformin, n i 5. ift. Beta cell preservation Sh 6. Early Insulin use m g i 7. Prevention; Intense Rx. d a r a 8. Pre DM (IFG, IGT), DM P 9. Blood vessel; guardian Rx. 10. DM = CAD; Prevention 11. Emphasis on complic. less 11. MAU, Micro, Macro com. 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 www. drsarma. in 50

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To Reiterate § Glycemic goal alone is not adequate at all § CAD must be prevented at all costs § Vascular Protection in DM is the only key § Statins in full dose Fibrate or Niacin § All T 2 DM must receive Guardian Rx. ACEi/ARB, ASA, Statin, TLC, PA, ↓ Weight www. drsarma. in 52

How foolish we are all !! Samudrae saanta kallole When the waves stop, then Snatum itcchati mooda dhi Shall I bathe, thinks the fool 53 Jagad guru Adi Sankarachraya www. drsarma. in

How foolish we are all !! Samudrae saanta kallole When the waves stop, then Snatum itcchati mooda dhi Shall I bathe, thinks the fool Samsaare saanta kallole Sans turbulance I am when, Jnanam icchati durmati Then shall I strive for wisdom 54 Jagad guru Adi Sankarachraya www. drsarma. in

How foolish we are all !! Samudrae saanta kallole When the waves stop, then Snatum itcchati mooda dhi Shall I bathe, thinks the fool Samsaare saanta kallole Sans turbulance I am when, Jnanam icchati durmati Then shall I strive for wisdom Sareerae hrid rogapeeditae The CAD strikes my heart when Roginah kaankshati rakshati Then, shall I crave for prevention 55 www. drsarma. in