1) The document discusses lipid abnormalities seen in patients with insulin resistance and diabetes, including elevated triglycerides, reduced HDL, and small dense LDL particles. 2) It explains the effects of insulin resistance on lipid metabolism in the liver and fat cells, increasing VLDL production and free fatty acid release from fat cells. 3) Lifestyle modifications and drug therapies are recommended to target specific lipid abnormalities, with statins as first choice for lowering LDL, niacin for raising HDL, and fibrates for lowering triglycerides.

1. 1
Speaker :DR. KAMIL ABBAS
AL ADWANI GENERAL HOSPITAL

2. 2
How to interpret ?

3. C
TG
B 100 + E +C
C
TG
B 100
C
T
G
A I, A II
HDL LDL
VLDL
TG
B 48+E+C
CM
3

4. Apolipoprotein B
Non-HDL-C
Measurements
TG rich particles
VLDL VLDLR IDL LDL SDL
Atherogenic Particles
4
Cholesterol rich

5.  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
5

6.  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
6

7. 7
Hypertension
Obesity
Hyperinsulinemia
Diabetes
Hyper triglyceridemia
Small, dense LDL
Low HDL
Hyper coagulability
Insulin
Resistance
Atherosclerosis

8. • Elevated total TG
• Reduced HDL
• Small, dense LDL
• ↑ HDL 3 and ↓ HDL1 and HDL 2
• LDL is not usually high
• Postprandial Hyper lipemia
8

9. Increased Decreased
• Triglycerides
• VLDL
• LDL, sLDL
• Apo B
• HDL
• Apo A-I
Dyslipidemia in DM and IRS
9

10. 10

11. 11

12. 12
Fat Cells Liver
Insulin
IR X
FFA

13. Fat Cells Liver
Insulin
IR X
 TG
 Apo B
 VLDL
VLDL
FFA
13

14. (hepatic
lipase)
Fat Cells Liver
Kidney
Insulin
IR X
(CETP)
CE
 TG
 Apo B
 VLDL
HDL
TG
Apo A-1
FFA
VLDL
14

15. (hepatic
lipase)
Fat Cells Liver
Kidney
Insulin
IR X
(CETP)
CE
 TG
 Apo B
 VLDL
(CETP)
HDL
(lipoprotein or hepatic lipase)
SD
LDL
LDL
TG
Apo A-1
TG
CE
FFA
VLDL
15

16. • 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
16

17. • 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
17
Austin MA et al. Curr Opin Lipidol 1996;7:167-171.

18.  1) Plays an important role
 2) Has no role
 3) Unsure
 4) Is only a tie breaker for people with
intermediate risk

19. 1.00
0.99
0.98
0.97
0.96
0.00
0 2 4 6 8
Years of Follow-up
CRP AND LDL IN THE WOMEN’S HEALTH
SURVEY
Ridker PM et al, N Engl J Med. 2002;347:1157-1165.
Probability
of
Event-free
Survival
Median LDL 124 mg/dl
Median CRP 1.5mg/l
low CRP – low LDL
high CRP – high LDL
low CRP – high LDL
high CRP – low LDL
CRP and
LDL interact
in risk
generation

20.  1) yes
 2) No
 3) Not sure

21. Rosuvastatin 20 mg (N=8901) MI
Stroke
Unstable
Angina
CVD Death
CABG/PTCA
4-week
run-in
Ridker et al, Circulation 2003;108:2292-2297.
No Prior CVD or DM
Men >50, Women >60
LDL <130 mg/dL
hsCRP >2 mg/L
Placebo (N=8901)
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica,
Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands,
Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland,
United Kingdom, Uruguay, United States, Venezuela
JUPITER DESIGN

23. 47%
Reduction
Unstable
angina
20%
Reduction
Mortality
44%
Reduction
CV events
54%
Reduction
Heart
attack
48%
Reduction
Stroke
43%
Reduction
VTE
Highlights

25. JUPITER
Tolerability and safety data
Adverse Events, (%)
Any serious adverse event 15.5 15.2 0.60
Muscle weakness, stiffness, pain 15.4 16.0 0.34
Myopathy 0.1 0.1 0.82
Rhabdomyolysis 0.0 <0.01* ----
Newly diagnosed cancer 3.5 3.4 0.51
Death from cancer 0.7 0.4 0.02
Gastrointestinal disorders 19.2 19.7 0.43
Renal disorders 5.4 6.0 0.08
Bleeding 3.1 2.9 0.45
Hepatic disorders 2.1 2.4 0.13
Other events, (%)
Newly diagnosed diabetes** 2.4 2.8 0.20
Haemorrhagic stroke 0.1 0.1 0.44
Placebo Rosuvastatin p-value
[n=8901] [n=8901]
*Occurred after trial completion; **physician reported newly diagnosed diabetes
Ridker PM et al. Am J Cardiol 2007; 100: 1659–1664.

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A New Paradigm !!!

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Recommendations

28.  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
28

29.  If all lipid values are normal
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
29

30.  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)
30

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 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

32. 32
 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 )

33. Drug Rx. – Effect on Lipoproteins
Pharmacological Agents LDL HDL TG
Statins (HMG CoA Reductase In)      
Fibrates (PPAR- γ Activators)     
BAR (Bile Acid Sequestering
Resins)
  
Niacin (Plain or SR)     
ADA. Diabetes Care 2003;26 (suppl 1):S 83-S 86
33

34. Statins
• Rosuvastati
n
• Atorvastati
n
• Simvastatin
• Lovastatin
• Pravastatin
• Cervistatin
Fibric Acid
• Fenofibrate
• Gemfibrozil
• Benzafibrat
e
• Clofibrate
• Ciprofibrat
e
• Clofibride
Niacin
• Neasyn SR
• Neasyn
• Nialip
• Neaspan
www.drsarma.in 34

35. 35
High LDL
Therapeutic Lifestyle Change
Add on drug - EZ , Niacin, BAR
Therapy of Choice: Statin
Drug Therapy

36. 36
Low HDL
Therapeutic Lifestyle Change
Add on drug - Finofibrate
Therapy of Choice : Niacin
Drug Therapy

37. 37
High TG
Therapeutic Lifestyle Change
Add on drug – Statin, Niacin
Therapy of Choice : Fibrate
Drug Therapy

38. www.drsarma.in 38
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