Академический Документы
Профессиональный Документы
Культура Документы
Slide 1
Problems and Challenges in Managing
Type 2 Diabetes Mellitus
The Problem
Atherosclerosis is a prominent but underappreciated complication
associated with diabetes mellitus
The Challenge
Therapies to reduce coronary heart disease (CHD) risk are
effective. Our challenge is to routinely apply the available
therapies to adult patients with diabetes mellitus, in conjunction
with appropriate glucose control
Adapted from Folsum AR et al Diabetes Care 1997;20:935-942; American Diabetes Association Diabetes Care 2002;
25(suppl 1):S33-S49.
Slide 2
Type 2 Diabetes Prevalence Is Projected to
Reach 300 Million by 2025
About 155 million adults worldwide diagnosed with diabetes in 2000
– 83 million women and 72 million men
Between 1995 and 2025, the prevalence of diabetes in adults will increase by 35% and
the number of people with diabetes will increase
by 122%
EUROPE ASIA
JAPAN
USA 2000: 30.8M 2000: 71.8M
2000: 6.9M
2000: 15M 2025: 38.5M 2025: 165.7M
AFRICA 2025: 8.5M
2025: 21.9M
AMERICAS 2000: 9.2M OCEANIA
(Ex-US)
2025: 21.5M 2000: 0.8M
2000: 20M
2025: 1.5M
2025: 42M
Adapted from King H et al Diabetes Care 1998;21:1414-1431.
Slide 3
Atherosclerosis Is Common
in Newly Diagnosed Diabetes Mellitus
Adapted from Amos AF et al Diabet Med 1997;14:S7-S85; Hill Golden S Adv Stud Med 2002;2:364-370; Haffner SM et al
N Engl J Med 1998;339:229-234; Sprafka JM et al Diabetes Care 1991;14:537-543.
Slide 4
Two-Thirds of People with Diabetes Die
of Cardiovascular Disease
40 37%*
33%
30
20%
20
10
n=437 n=2699 n=183 n=743
0
Men Women
1 Year, hospitalized and nonhospitalized
MI = myocardial infarction
Time post-first MI
*p<0.001
Adapted from Miettinen H et al Diabetes Care 1998;21:69-75.
Slide 6
People with Diabetes Have MI Risk Levels
Comparable to People with Prior MI
25
20%
or nonfatal MI (%)
19%
Incidence of fatal
20
15
10
0
Diabetes (no prior MI) Prior MI (no diabetes)
(n=890) (n=69)
Patient type
Patients with diabetes without previous MI have as high of a risk of MI as
nondiabetic patients with previous MI.
These data provide a rationale for treating cardiovascular risk factors in diabetic
patients as aggressively as in nondiabetic patients with prior MI.
Adapted from Haffner SM et al N Engl J Med 1998;339:229-234.
Slide 7
People with Diabetes Have Increased
Cardiovascular Risk Factors
+ = moderately increased compared with nondiabetic population; ++ = markedly increased compared with nondiabetic population;
– = no increase compared with nondiabetic populations; LDL = low-density lipoprotein; apoB = apolipoprotein B; HDL = high-
density lipoprotein
Adapted from Chait A, Bierman EL. In: Joslin's Diabetes Mellitus. 13th ed. Philadelphia: Lea & Febiger, 1994:648-664.
Slide 8
Greater Risk of Death with Diabetes and
One Risk Factor than without Diabetes and
Three Risk Factors*
140 Diabetes
No diabetes
10,000 person-years
120
Age-adjusted CVD
death rate per
100
80
60
40
20
0
None One only Two only All three
Risk factors
*Serum cholesterol >200 mg/dl, smoking, systolic blood pressure >120 mmHg
Adapted from Stamler J et al Diabetes Care 1993;16:434-444.
Slide 9
Patients with Diabetes and Low Cholesterol
Had Higher Risk of CV Mortality than Those
without Diabetes and High Cholesterol
160 Diabetes
No diabetes
10,000 person-years
140
CV mortality per
120
100
80
60
40
20
0
<4.7 4.7–5.1 5.2–5.7 5.8–6.2 6.3–6.7 6.8–7.2 >7.3
CV = cardiovascular
Adapted from Stamler J et al Diabetes Care 1993;16:434-444.
Slide 10
“Normal” LDL-C Levels in People with Diabetes Can Be Misleading...
Small, Dense LDL-C Particles Are More Atherogenic
Small, dense
LDL with more
apoB
Adapted from Austin MA, Edwards KL Curr Opin Lipidol 1996;7:167-171; Austin MA et al JAMA 1988;260:1917-1921;
Sniderman AD et al Diabetes Care 2002;25:579-582.
Slide 11
In People with Diabetes Macrovascular
Complications Are Two Times Greater than
Microvascular Complications
25
People with diabetes developing
20%
9 years of diagnosis (%)
20
complications within
15
10 9%
n=5102 n=5102
0
Macrovascular complications Microvascular complications
These data support the need for reducing LDL-C to lower CHD risk
in people with diabetes mellitus. Glucose control is also important in
reducing the risk of microvascular complications.
Adapted from American Diabetes Association Diabetes Care 2002;25(suppl 1):S33-S49; American Diabetes Association
Diabetes Care 2002;25(suppl 1):S74-S77.
Slide 15
Lipid Guidelines for Patients with Diabetes
European Societies
*CHD risk ≥ 20% over 10 years or will exceed 20% if projected to age 60
Adapted from Wood D et al Atherosclerosis 1998;140:199-270.
Slide 16
Lipid Guidelines for Patients with Diabetes
National Cholesterol Education Program (NCEP)
Intensive CHD prevention strategy is warranted [for patients with diabetes],
with LDL-C as a primary treatment target
Adapted from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults JAMA 2001;
285:2486-2497.
Slide 17
Lipid Guidelines for Patients with Diabetes
International Atherosclerosis Society
“Patients with diabetes experience significant cardiovascular disease risk
reduction with control of other risk factors . . . including LDL-C.”
*High-risk patients include those with established CHD (history of MI, stable or unstable angina, or coronary artery
procedures), noncoronary forms of atherosclerotic disease, or multiple risk factors (10-year risk >20%).
**Risk factors that modify LDL-C goals are smoking, hypertension, low HDL-C, and advanced age (men ≥ 45 years;
women ≥ 55 years).
Adapted from International Atherosclerosis Society Harmonized Clinical Guidelines on Prevention of Atherosclerotic Vascular
Disease. Available at: http://www.athero.org/download/guidelines.pdf.
Slide 18
Heart Protection Study
Diabetes Sub-Study
Almost 6000 men and women, aged 40–80 years with diabetes mellitus
– 1981 persons with history of CHD
– 3982 persons with no history of CHD
People randomized to simvastatin 40 mg or placebo
Mean duration of follow-up 5 years
Objective—to evaluate the long-term benefits of simvastatin and/or
antioxidants in people with diabetes with or without CHD regardless
of cholesterol level
Primary endpoints—first major coronary events* and first major vascular
events**
Statin not considered clearly indicated or contraindicated by patients’ primary
physicians
*Nonfatal MI or death from coronary disease
**Major coronary events, stroke of any type, and coronary or noncoronary revascularizations
Adapted from Heart Protection Study Collaborative Group Eur Heart J 1999;20:725-741; Heart Protection Study
Collaborative Group Lancet 2002;360:7-22; Heart Protection Study Collaborative Group Lancet 2003;361:2005-2016.
Slide 19
Impact of Simvastatin on LDL-C
Nine Out of 10 Patients with Diabetes Achieved Goal*
100 92% 91%
80
Patients (%)
60
40
20
n=3985** n=1978**
0
Without CHD With CHD
Results from the five-year Heart Protection Study (HPS) of almost 6000 patients with
diabetes with or without CHD indicated that 92% of patients with diabetes, but without
CHD, and 91% of patients with CHD who received simvastatin 40 mg achieved
the European Guidelines LDL‑C treatment goal of <3 mmol/L (115 mg/dl)***
*By the four-month point in HPS
**These populations differ from those reported in later HPS publications (3982 and 1981) because three patients were
reclassified after the four-month point. The percentages of patients achieving LDL-C goal are not affected.
***Based on random sampling of patients with diabetes
Adapted from Armitage J, Collins R Heart 2000;84:357-360.
Slide 20
Impact of Simvastatin on First Major Vascular Events
All Patients and Patients with Diabetes
Placebo
Simvastatin
24% risk reduction 22% risk reduction
(p<0.0001) (p<0.0001)
30
25.2 25.1
Patients with major
vascular events
20.2
by year 5 (%)
19.8
20
2585 748
patients 2033 patients 601
10 with events patients with events patients
with events with events
400 371
360
subsequent major vascular
events per 1000 patients
Number of first and
300 286
269
by year 5
2585 748
200 patients patients
2033 601
with 3697 patients with 1109 patients
events with 2763 events with 852
100 events events
24% 10.4
by year 5 (%)
10
9.4 risk reduction**
8.7
6.5
5.0
5
15 13.5
Patients with major
vascular events
by year 5 (%)
10 9.3
n=1457 n=1455
0
Placebo Simvastatin
20.9
20
Patients with major
(p=0.05)
by year 5 (%)
15.7
15
11.1
10 8.0
22.6 22.6
Patients with major
vascular events
by year 5 (%)
20 18.3
10
22%
Patients with major vascular
10 10
*p<0.05
21%
risk reduction* 21%
Patients with major vascular
40 40 risk reduction*
31.6
events by year 5 (%)
10 10
*p<0.05
100
10
Patients (%)
8
6 5.1% 4.8%
4
2
0
Placebo Simvastatin
(n=10,267) (n=10,269)
Discontinuations due to any adverse event
Year 1 2 3 4 5 6
Simvastatin 40 mg 5 6 6 6 6 7
Placebo 5 6 6 6 7 7
*Myopathy defined as muscle symptoms plus creatine kinase >10 times the upper limit of normal
Adapted from Heart Protection Study Collaborative Group Lancet 2002;360:7-22.
Slide 30
In 20,000 Patients in HPS
Simvastatin 40 mg Helped Preserve
Renal Function
–20%
(p<0.0001)
10 8.9%
creatinine concentration
8 7.1%
0
Placebo Simvastatin
(n=7697) (n=7999)
Adapted from Heart Protection Study Collaborative Group Lancet 2003;361:2005-2016.
Slide 31
Lipid Lowering in Patients with Diabetes
Conclusions
Patients with diabetes have a substantial number of CHD events,
and many do not survive their first MI
LDL-C has been identified in UKPDS and by all major guidelines
as a primary target for reducing CHD risk in patients with diabetes
In UKPDS, intensive glucose control significantly reduced microvascular
events such as retinopathy; however, it produced
a modest and nonsignificant reduction in macrovascular events,
such as MI and stroke
Patients with diabetes need lipid-lowering therapy because effective
management of blood glucose only modestly improves plasma levels
of LDL-C or HDL-C; this improvement frequently does not meet levels
recommended by guidelines
Adapted from American Diabetes Association Diabetes Care 2002;25(suppl 1):S33-S49; Miettinen H et al Diabetes Care
1998;21:69-75; Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults JAMA 2001;285:
2486-2497; United Kingdom Prospective Diabetes Study Group Lancet 1998;352:837-853; American Diabetes Association
Diabetes Care 2002;25(suppl 1):S74-S77; Wood D et al Atherosclerosis 1998;140:194-270.
Slide 32
Heart Protection Study
Major Medical Conclusions
In almost 6000 patients with diabetes
Over 90% reached the European Guidelines LDL-C goal
on simvastatin 40 mg*
Simvastatin significantly reduced the risk of
– major vascular events by 22% (p<0.0001)
– stroke by 24% (p=0.01)
– revascularization by 17% (p=0.02)
Benefits of simvastatin were evident regardless of CHD history, blood
glucose control, baseline LDL-C, hypertension status, obesity, age, and
gender
Simvastatin therapy was well tolerated and had a safety profile
comparable to placebo
*By the four-month point in HPS, based on random sampling of patients with diabetes
Adapted from Heart Protection Study Collaborative Group Lancet 2002;360:7-22; Armitage J, Collins R Heart
2000;84:357-360; Heart Protection Study Collaborative Group Lancet 2003;361:2005-2016.
Slide 33
Heart Protection Study
Medical Implications
Based on the results of HPS, simvastatin 40 mg daily should
be considered routinely for patients with diabetes
– Simvastatin 40 mg is the only statin proven in a wide range
of patients with diabetes to
reduce the risk of major coronary events
reduce the risk of stroke
reduce the risk of both coronary and noncoronary
revascularization
reduce the risk of developing peripheral macrovascular
complications (including peripheral revascularization,
limb amputations, and leg ulcers)
Adapted from Powers AC. In Harrison’s Principles of Internal Medicine. 15th ed. New York: McGraw-Hill, 2001:2109-2137;
American Diabetes Association Diabetes Care 2002;25(suppl 1):S74-S77.
Slide 35
References
Please refer to notes page.
Slide 36
References (cont’d)
Please refer to notes page.
Slide 37