www.drsarma.in 1

Dr. R. V. S. N. Sarma., Dr. R. V. S. N. Sarma., M.D., M.Sc., M.D., M.Sc., (Canada)(Canada)

Consultant Physician and Chest Consultant Physician and Chest SpecialistSpecialist

www.drsarmwww.drsarma.ina.in

2

Sutton-Osler-Rendu-Weber-Syndrome (HHT)

Tsutsugamushi fever Criggler Najar Syndrome

Diabetes Mellitus – DiagnosisPrevention, Complications andModern Management

www.drsarma.in 3

• Saare jehan se achchaa …….Hindustan hamara…

• Saare jehan se oonchaa …….T2DM hamara hamara…

• Saare jehan se oonchaa …….CADI hamara 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

• Indian CAD is 10 years younger, Often silent MI

• TVD, DVD, SD, MACE are more in Indians

4www.drsarma.in

www.drsarma.in 5

DIABETOLOGIST IS DEAD !!

METABOLOGIST IS BORN !!

The Islet, Vol 3, No2, May 2005

6www.drsarma.in

7www.drsarma.in

www.drsarma.in 8

Atherosclerosis and Insulin Resistance

HypertensionHypertension

ObesityObesity

HyperinsulinemiaHyperinsulinemia

DiabetesDiabetes

Hyper triglyceridemiaHyper triglyceridemia

Small, dense LDLSmall, dense LDL

Low HDLLow HDL

Hyper coagulabilityHyper coagulability

InsulinInsulinResistanceResistance

InsulinInsulinResistanceResistance AtherosclerosisAtherosclerosisAtherosclerosisAtherosclerosis

9www.drsarma.in

www.drsarma.in 10

www.drsarma.in 11

www.drsarma.in 12

www.drsarma.in 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

Micro and Macrovascular Onslaught

14www.drsarma.in

Ticking Clock of T2DM1. Micro-vascular (DR, CKD, DPN, DAN)

At the onset of hyperglycemia Control of hyperglycemia essential The A1c target of less than 7 must (A)

2. Macro-vascular (CAD, CVD, PVD) VP At the onset of insulin resistance Blood pressure goal of 130/80 (B) Control of lipid abnormalities (C)

15www.drsarma.in

16www.drsarma.in

What types of lesions cause MI ?

Falk E, et al. Circulation. 1995;92:657-671.

100100

8080

6060

4040

2020

00

14%14%

18%18%

68%68%

All fourAll fourstudiesstudies

50%-70%<50% >70%

100100

6060

4040

2020

00AmbroseAmbrose

19881988LittleLittle19881988

NobuyoshiNobuyoshi19911991

GiroudGiroud19921992

Cor

onar

y st

enos

is (

%)

Cor

onar

y st

enos

is (

%)

Coronary stenosis severity prior to MICoronary stenosis severity prior to MI

8080

17www.drsarma.in

What types of lesions cause MI ?

Falk E, et al. Circulation. 1995;92:657-671.

100100

8080

6060

4040

2020

00

14%14%

18%18%

68%68%

All fourAll fourstudiesstudies

50%-70%<50% >70%

100100

6060

4040

2020

00AmbroseAmbrose

19881988LittleLittle19881988

NobuyoshiNobuyoshi19911991

GiroudGiroud19921992

Cor

onar

y st

enos

is (

%)

Cor

onar

y st

enos

is (

%)

Coronary stenosis severity prior to MICoronary stenosis severity prior to MI

8080

18www.drsarma.in

Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.

CV Risk Factors in Diabetes

3.2

2.3

6.5

10.0

0

2

4

6

8

10

12

Microalbuminuria Smoking Diastolic BP Cholesterol

Od d

s R

a tio

19www.drsarma.in

Causes of death in Diabetes

20www.drsarma.in

DM – Strongest RF for CVD

21www.drsarma.in

Years after DM Diagnosis

≤ 2 3-5 6-9 10-14 15+

15%

21%24%

29%

48%

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.

Duration of T2DM and CVD

22www.drsarma.in

Duration of DM - CV Mortality

0

0.5

1

1.5

2

2.5

3

3.5

4

< 5 6 to 10 11 to 15 16 to 25 26 +

Duration of Diabetes (years)

p for trend <0.001

Cho, et al. J Am Coll Card 2002:40:954.

Rel

ativ

e R

isk

23www.drsarma.in

Life Expectancy with Diabetes

Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.

0102030405060708090

Men Women

YearsDMNo DM

0200400600800

1000120014001600

Mortality rate/100,000

DiabetesNo Diabetes

24www.drsarma.in

Cardiovascular Disease and T2DM

Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.

0%

5%

10%

15%

20%

Hypertension Heart Disease

Pre

vale

nce

of C

V D

isea

se

Diabetes

No Diabetes

25www.drsarma.in

Clinical Outcome for Diabetes

4-year Follow-up

0

2

4

6

8

10

12

14

CV Death MI Stroke Dialysis

%

HOPE / MICRO-HOPE. Lancet 2000;355:253.

26www.drsarma.in

ACS and Diabetes – Up to 1 Year

% o

f pa

tient

s

1.83.9

7.1

8.9 7.9

14.4 14.1

21.3

P<0.0001

P=0.035

P<0.0001

P<0.0001

0

5

10

15

20

25

In-Hospital

Mortality

Non-fatal MI 1-y All-Cause

Mortality

1-y

Mortality/MI

N = 3429

N = 1149

No Diabetes

Diabetes

Yan R, et al. Can J Cardiol 2003;19(suppl A):260A.

27www.drsarma.in

OASIS Study: Total Mortality

3 6 9 12 15 18 21 24

0.25

0.20

0.15

0.10

0.05

0.0

Months

Eve

nt

rate

RR = 2.88 (2.37-3.49)

RR=1.99 (1.52-2.60)

RR=1.71 (1.44-2.04)

RR=1.00

Malmberg K, et al. Circulation 2000;102:1014–1019.

Diabetes/CVD +, (n = 1148)

No Diabetes/CVD +, (n = 3503)

Diabetes/CVD -, (n = 569)

No Diabetes/CVD -, (n = 2796)

28www.drsarma.in

Predictors of CV Risk in DM

29www.drsarma.in

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

30www.drsarma.in

Two Sides of the Coin

31www.drsarma.in

Apolipoprotein BApolipoprotein BNon-HDL-CNon-HDL-C

MeasurementsMeasurements

TG rich particlesTG rich particles

VLDLVLDL VLDLRVLDLR IDLIDL LDLLDL SDLSDL

Atherogenic Particles

www.drsarma.in 32

Cholesterol richCholesterol rich

Today’s Safer ValuesTotal 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

33www.drsarma.in

• 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

Dyslipidemia in DM and IRS

34www.drsarma.in

Dyslipidemia based on TG and LDL

35www.drsarma.in

• 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

Small Dense LDL and CHD Potential Atherogenic Mechanisms

Austin MA et al. Curr Opin Lipidol 1996;7:167-171.

36www.drsarma.in

37www.drsarma.in

38www.drsarma.in

39www.drsarma.in

40www.drsarma.in

www.drsarma.in 41

2004

AA A1c (Hb A1c)A1c (Hb A1c)

BB Blood pressure Blood pressure (goal)(goal)

CC Cholesterol (all Cholesterol (all lipids)lipids)

42www.drsarma.in

is hopelessly is hopelessly inadequate !!inadequate !!

43www.drsarma.in

1. ACE inhibitors or ARBs2. ASA (Acetyl Salicylic Acid)3. Atorvastatin (Lipid management)4. A1c control (Glycemic control)5. Blood pressure goal (<130/80)6. Control of Nephropathy, Proteinuria

(MAU)7. Cigarette smoking cessation8. Weight and waist management9. Physical Activity – at least 2 km/d x

5 d

Goals inT2DM for VP

Risk FactorRisk Factor Goal or TargetGoal 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

44www.drsarma.in

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 Inflammation45www.drsarma.in

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

46www.drsarma.in

• 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

MNT and Dyslipidemia

47www.drsarma.in

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

Priorities for Treatment

48www.drsarma.in

www.drsarma.in 49

Diabetes as of now1.Cardiometabolic disease2.Hb A1c, FBG, PPBG

3. Insulin Resistance, ID4.Metformin, Glitazones5.Beta cell preservation6.Early Insulin use7.Prevention; Intense Rx.8.Pre DM (IFG, IGT), DM9.Blood vessel; guardian

Rx.10.DM = CAD; Prevention11.MAU, Micro, Macro com.

About 10 to 15 years ago

1.Only Dysglycemia2.Urine, RBG, GTT3. Insulin deficiency4.Secretagogues – SU5. cell stimulation6. Insulin as a last resort7.Treatment of DM only8.BG > 180, No IFG, IGT9.Blood Sugar Disease10.DM is a mild disease

11.Emphasis on complic. less

www.drsarma.in 50

www.drsarma.in

51

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 T2DM must receive Guardian Rx.

ACEi/ARB, ASA, Statin, TLC, PA, ↓ Weight

To Reiterate

52www.drsarma.in

www.drsarma.in53

Samudrae saanta kallole

Snatum itcchati mooda dhi

When the waves stop, then

Shall I bathe, thinks the fool

Jagad guru Adi Sankarachraya

www.drsarma.in54

Samudrae saanta kallole

Snatum itcchati mooda dhi

Samsaare saanta kallole

Jnanam icchati durmati

When the waves stop, then

Shall I bathe, thinks the fool

Sans turbulance I am when,

Then shall I strive for wisdom

Jagad guru Adi Sankarachraya

www.drsarma.in55

Samudrae saanta kallole

Snatum itcchati mooda dhi

Samsaare saanta kallole

Jnanam icchati durmati

Sareerae hrid rogapeeditae

Roginah kaankshati rakshati

When the waves stop, then

Shall I bathe, thinks the fool

Sans turbulance I am when,

Then shall I strive for wisdom

The CAD strikes my heart when

Then, shall I crave for prevention