1. Dr. R. V. S. N. Sarma., M.D., M.Sc., (Canada)
Consultant Physician and Chest Specialist
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3. www.drsarma.in 3

4. What types of lesions cause MI ?
Coronary stenosis severity prior to MI
100 100
14%
80 80
Coronary stenosis (%)
18%
60 60 68%
40 40
20 20
0 0
Ambrose Little Nobuyoshi Giroud All four
1988 1988 1991 1992 studies
<50% 50%-70% >70%
Falk E, et al. Circulation. 1995;92:657-671.
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5. What types of lesions cause MI ?
Coronary stenosis severity prior to MI
100 100
14%
80 80
Coronary stenosis (%)
18%
60 60 68%
40 40
20 20
0 0
Ambrose Little Nobuyoshi Giroud All four
1988 1988 1991 1992 studies
<50% 50%-70% >70%
Falk E, et al. Circulation. 1995;92:657-671.
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6. CV Risk Factors in Diabetes
12
10.0
10
8
Odds Ratio
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.
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7. Causes of death in Diabetes
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8. Why is it so ?
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9. DM – Strongest RF for CVD
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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.
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11. Duration of DM - CV Mortality
4 p for trend <0.001
3.5
Relative Risk
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.
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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
10 200
0 0
Men Women Mortality rate/100,000
Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.
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13. Cardiovascular Disease and T2DM
20%
Prevalence of CV Disease
Diabetes
15%
No Diabetes
10%
5%
0%
Hypertension Heart Disease
Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.
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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.
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15. ACS and Diabetes – Up to 1 Year
25
P<0.0001
No Diabetes
20 21.3
% of patients
N = 3429
Diabetes P<0.0001
15 N = 1149
14.4 14.1
P=0.035
10
8.9 7.9
P<0.0001 7.
5 1
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.
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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)
Event rate
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.
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17. Predictors of CV Risk in DM
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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
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19. How to interpret ?
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20. Lipoproteins
HDL LDL
C C
T TG
G
A I, A II B 100
VLDL CM
TG TG
C
B 100 + E +C B 48+E+C
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21. Atherogenic Particles
Non-HDL-C
Measurements Apolipoprotein B
VLDL VLDLR IDL LDL SDL
TG rich particles Cholesterol rich
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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
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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
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24. What are the Mechanisms ?
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25. Atherosclerosis and Insulin Resistance
Hypertension
Obesity
Hyperinsulinemia
Insulin
Insulin Diabetes
Atherosclerosis
Atherosclerosis
Resistance
Resistance Hyper triglyceridemia
Small, dense LDL
Low HDL
Hyper coagulability
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26. Insulin Resistance - Clinical Clues
• Abdominal obesity
• ↑ TG + ↓ HDL-C
• Glucose intolerance
• Hypertension
• Atherosclerosis
• Ethnicity (Indians, Negroid races)
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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
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28. Dyslipidemia in DM and IRS
Increased Decreased
• Triglycerides • HDL
• VLDL • Apo A-I
• LDL, sLDL
• Apo B
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29. Dyslipidemia based on TG and LDL
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30. Dyslipidemia based on TG and Apo B
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31. Mechanisms of DM Dyslipidemia
Fat Cells Liver
FFA
IR X
Insulin
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32. Mechanisms of DM Dyslipidemia
Fat Cells Liver
FFA
 TG VLDL
 Apo B
IR X  VLDL
Insulin
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33. Mechanisms of DM Dyslipidemia
Fat Cells Liver
FFA CE
 TG (hepatic
VLDL (CETP) HDL
 Apo B lipase)
IR X  VLDL TG
Apo A-1
Kidney
Insulin
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34. Mechanisms of DM Dyslipidemia
Fat Cells Liver
FFA CE
 TG (hepatic
VLDL (CETP) HDL
 Apo B lipase)
IR X  VLDL TG
Apo A-1
CE (CETP) TG
Kidney
Insulin
SD
LDL
LDL
(lipoprotein or hepatic lipase)
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35. IR and TG Increase
625
r = 0.73
500 P < 0.0001
Plasma TG (mg/dL)
400
300
200
100
100 200 300 400 500 600
Insulin Response to Oral Glucose
Olefsky JM et al. Am J Med. 1974;57:551-560.
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36. DM, IRS and HDL
Hyperinsulinemic
P < 0.005
Normoinsulinemic
HDL-C (mg/dL)
P < 0.005
Non-obese Obese
Reaven GM. In: Le Roith D et al., eds. Diabetes Mellitus.1996:509-519.
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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
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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.
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39. What the studies say ?
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44. www.drsarma.in 44

45. Clear Excess mortality in DM
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46. A New Paradigm !!!
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47. is hopelessly inadequate !!
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48. A A1c (Hb A1c)
B Blood pressure (goal)
C Cholesterol (all lipids)
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49. Ticking Clock of T2DM
1. Micro-vascular (DR, DKD, DPN, DAN)
 At the onset of hyperglycemia
 Control of hyperglycemia essential
 The A1c target of less than 7 must (A)
1. Macro-vascular (CAD, CVD, PVD)
 At the onset of insulin resistance
 Blood pressure goal of 130/80 (B)
 Control of lipid abnormalities (C)
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50. www.drsarma.in 50

51. Goals inT2DM for VP
Risk Factor Goal or Target
Glycemia Hb A1c < 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/m2
Physical activity At least 5 days - 2 km/day
ADA, CDA, IDF, WWD
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52. 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
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53. ACEi in T2DM - VP
• Antihypertensive, vasoprotective, antithrombotic, 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
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54. Recommendations
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55. 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
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56. Priorities for Treatment
 If all lipid values are normal
1. Lifestyle interventions (TLC)
MNT, Physical Activity, Weight and Waist reduction
1. Statin in a minimum dose of 10 mg o.d
2. Follow up every one year by full lipid profile
3. All Indians must be tested for LP(a) and
If > 30 mg% - Niacin SR 350 to 500 mg started
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57. Priorities for Treatment
 LDL cholesterol lowering – First priority
1. Lifestyle interventions (TLC)
2. Drugs - First choice – Statin with or without
3. Cholesterol absorption inhibitors (EZ)
4. Second choice – Niacin and Fibrate
5. Add on – BAR (Bile acid binding resins)
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58. Priorities for Treatment
 HDL cholesterol raising – Second priority
1. Lifestyle interventions
2. First choice - Niacin ( doses <2 g/day)
3. Preferably short acting Niacin
4. Fibrates are second choice
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59. Priorities for Treatment
 Triglyceride lowering – Third priority
1. First choice: Lifestyle interventions
2. Glycemic control is the best Rx for ↓TG
3. Fibrates
4. Niacin
5. High dose statins (if LDL is also high )
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60. Priorities for Treatment
 Triglyceride Lowering (continued)
• In case of severe hyper triglyceridemia (> 1000 mg),
severe fat restriction (< 10 % of calories ) in
addition to pharmacological therapy is necessary to
reduce the risk of pancreatitis and lipemia effects
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61. Priorities for Treatment
 Combined Dyslipidemia
1. First choice: Glycemic control + Statin
2. Glycemic control+ Statin + Fibrate
3. Glycemic control+ Statin + Niacin
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62. Drug Rx. – Effect on Lipoproteins
ADA. Diabetes Care 2003;26 (suppl 1):S 83-S 86
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63. Drugs for Dyslipidemia
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64. Treatment of  LDL
High LDL
Therapeutic Lifestyle Change
Drug Therapy
Therapy of Choice: Statin
Add on drug - EZ , Niacin, BAR
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65. Treatment of  HDL
Low HDL
Therapeutic Lifestyle Change
Drug Therapy
Therapy of Choice : Niacin
Add on drug - Finofibrate
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66. Treatment of  TG
High TG
Therapeutic Lifestyle Change
Drug Therapy
Therapy of Choice : Fibrate
Add on drug – Statin, Niacin
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67. Anti Diabetic Drugs and Lipids
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69. Anti HT Drugs and Lipids
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70. To Reiterate
 Glycemic goal alone is not adequate at all
 CAD must be prevented at all costs
 The A, B, C of Diabetes must be addressed
 Statins in full dose ± Fibrate or Niacin
 All T2DM must receive drugs/advise on
 ACEi/ARB, ASA, Statin, TLC, PA, ↓ Weight
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