Type 2 Diabetics are at Increased Risk of Cardiovascular Disease

1
Type 2 Diabetics are at Increased Risk of
Cardiovascular Disease
lt4.7 (lt180)
5.25.7 (200220)
6.26.7 (240260)
lt7.2 (gt280)
Plasma cholesterol, mmol/L (mg/dL)
Data from MRFIT study. Stamler J et al. Diabetes
Care 199316434444.
2
Diabetic Subjects are at High Risk of
FutureCoronary Events
Diabetic patients without previous MI have as
high a risk of MIas nondiabetic patients with
previous MI
Nondiabetic without prior MI Diabetic without
prior MI Nondiabetic with prior MI Diabetic with
prior MI
Graph shows Kaplan-Meier survival curves for CHD
mortality in 1059 subjects with Type 2 diabetes
and 1378 nondiabetic subjects. Error bars 95
confidence intervals. Haffner SM et al. N Engl J
Med 1998339(4)229234.
3
Normal Coordinationof Postprandial
LipidMetabolism by Insulin
Postprandial LipidMetabolism in
InsulinResistance
Adipose Tissue
Adipose Tissue
Insulin Inhibits
FFA
Accelerated
FFA
Liver
Liver
Intestine
Intestine
Accelerated
TG
TG
FC
AdiposeTissueCapillary Endothelium
AdiposeTissueCapillary Endothelium
HDL
HDL
CM
VLDL
CM
VLDL
CE
TG
LPL
CE
TG
LPL
Insulin Accelerates
Insulin Activation Impaired
Remnants (to Liver)
Remnants (to Liver)
FFAfree fatty acid CMchylomicron
LPLlipoprotein lipase CEcholesteryl ester R.
Camena after Frayn.
4
Lipid Abnormalities in NIDDM
Lipid or Poor glycemic Good glycemiclipoprotein c
ontrol control Total-C Increased Normal or
decreased TG Markedly increased Increased VLDL-C M
arkedly increased Increased LDL-C Increased Norma
l HDL-C Reduced Reduced
Adapted from Taskinen MR. Ballières Clin
Endocrinol Metab 19904743775.
5
Changes Associated with Diabetic Dyslipidemia

• Composition and size of lipoproteins (small,
  dense LDL)
• Enzymatic activity ( ? LPL, ? hepatic lipase)
• Reverse cholesterol transport
• Glycosylation of apolipoproteins
• Oxidation of lipoproteins
• Elevation and modification of Lp(a)

6
American Diabetes Association (ADA)Recommendation
s for Adults with Type 2 Diabetes

• Primary therapy should be directed first at
  lowering LDL-C levels

Initiate therapy LDL-C goal With CHD, PVD or
CVD gt100 mg/dL ?100 mg/dL (2.6 mmol/L) (2.6
mmol/L) Without CHD, PVD or CVD ?130 mg/dL ?100
mg/dL (3.4 mmol/L) (2.6 mmol/L)
ADA. Diabetes Care 199922(Suppl 1)556559.
7
Treatment of Dyslipidemia in Diabetes

• Abnormalities of lipid metabolism are frequent in
  type 1 and type 2 diabetes and may contribute to
  CHD risk
• No prospective intervention studies are currently
  available which document that treatment of
  dyslipidemia reduces CHD risk in the diabetic
  patient
• However, subanalyses from several landmark
  studies indicate that HMG-CoA reductase
  inhibitors reduce the risk of major coronary
  events in patients with diabetes
• Several clinical trials investigating the effects
  of atorvastatin on clinical outcome in type 2
  diabetes are underway

With simvastatin and pravastatin.
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Atorvastatin vs Simvastatin in Type 2 Diabetics
Effects on lipids at 4 Weeks
Atorvastatin 10 mg (n13)

Simvastatin 10 mg (n12)

Total-C
LDL-C
TG
HDL-C
Plt0.01 vs simvastatin. Best JD et al. Diab Nutr
Metab 199697480.
9
Efficacy of Atorvastatin in Type 2 Diabetics with
Concurrent Hyperlipidemia
Change in lipid profiles from baseline
LDL-C
Total-C
TG
ApoB
Non-HDL-C/HDL-C
Atorvastatin administered at 10 mg/day dose. Data
are from a pooled analysis of 156 patients with
type 2 diabetes. Bakker-Arkema R et al.
Presented at the 4th International Symposium on
Multiple Risk Factors in Cardiovascular Disease,
2325 April 1997, Washington DC, USA.
10
Efficacy of Atorvastatin in Type 2 Diabetics with
Concurrent Hyperlipidemia
Percent of patients (n88) reaching an LDL-C
targetof ?2.6 mmol/L (100 mg/dL)
Atorvastatin dose 10 mg/day 20 mg/day 40
mg/day 80 mg/day
Results from a 32-week, open-label study.
Non-responders were titrated to the next highest
dose at 4-week intervals. Responders maintained
the same dosage regimen for 16 weeks of
treatment. All patients who completed the study
reached target. Mean baseline LDL-C was 4.6
mmol/L (178 mg/dL). Aguilar-Salinas CA et al.
Atherosclerosis 1999In press.