www.drsarma.in 1. dr. r. v. s. n. sarma., m.d., m.sc., (canada) consultant physician and chest...
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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
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Sutton-Osler-Rendu-Weber-Syndrome (HHT)
Tsutsugamushi fever Criggler Najar Syndrome
Diabetes Mellitus – DiagnosisPrevention, Complications andModern Management
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• 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
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DIABETOLOGIST IS DEAD !!
METABOLOGIST IS BORN !!
The Islet, Vol 3, No2, May 2005
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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
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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
Micro and Macrovascular Onslaught
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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)
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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
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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
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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
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Causes of death in Diabetes
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DM – Strongest RF for CVD
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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
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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
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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
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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
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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.
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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.
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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)
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Predictors of CV Risk in DM
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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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Two Sides of the Coin
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Apolipoprotein BApolipoprotein BNon-HDL-CNon-HDL-C
MeasurementsMeasurements
TG rich particlesTG rich particles
VLDLVLDL VLDLRVLDLR IDLIDL LDLLDL SDLSDL
Atherogenic Particles
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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
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• 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
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Dyslipidemia based on TG and LDL
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• 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.
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2004
AA A1c (Hb A1c)A1c (Hb A1c)
BB Blood pressure Blood pressure (goal)(goal)
CC Cholesterol (all Cholesterol (all lipids)lipids)
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is hopelessly is hopelessly inadequate !!inadequate !!
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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
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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
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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
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• 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
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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
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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
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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
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Samudrae saanta kallole
Snatum itcchati mooda dhi
When the waves stop, then
Shall I bathe, thinks the fool
Jagad guru Adi Sankarachraya
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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
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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