Diabetic
Dyslipidemia
| The
impact of heart disease on people with diabetes is significant.
|
 |
Nearly 75%
of deaths among diabetics are directly attributable to CHD |
|
Type 1 and
type 2 diabetes are associated with a two- to fourfold increased
risk of CHD |
|
There is a
high 1-year mortality rate following a first MI: 44% in diabetic
men, 37% in diabetic women |
|
Cardiovascular
complications are the most significant cause of health care expenditures |
|
A major challenge
in the treatment of patients with diabetes is to reduce the risk
of cardiovascular disease. |
CHD Risk Factor
|
CHD is the
leading cause of death among patients with type 2 diabetes. |
|
Patients with
type 2 diabetes frequently have dyslipidemia, which may contribute
significantly to accelerated coronary atherosclerosis. |
|
Because risk
factors for heart disease are believed to be additive and perhaps
multiplicative, mild degrees of dyslipidemia may increase CHD risk. |
|
Controlling
dyslipidemia should be given equal emphasis as controlling hyperglycemia
when developing strategies for managing type 2 diabetes. |
Death From CHD:
Diabetics Without Prior MI Face Similar Risks as Nondiabetics With Prior
MI
Type 2 diabetes
is associated with a marked increase in the risk of CHD. It has been
debated whether patients with diabetes who have not had MIs should be
treated as aggressively for cardiovascular risk factors as patients
who have had MIs. In support of aggressive care are findings that diabetic
patients without previous MIs have as high a risk of death from CHD
as nondiabetic patients who have had a previous MI. ATP III now defines
diabetes as a CHD risk equivalent.
ADA
Rationale for Treatment of Dyslipidemia
|
People with
diabetes have a two to fourfold increased risk of CHD because of
various risk factors, including dyslipidemia. |
|
Diabetic dyslipidemia
is frequently characterized by elevated triglycerides, decreased
HDL levels, and a preponderance of small, dense LDL particles. |
|
Aggressive
therapy to treat diabetic dyslipidemia may reduce the risk of CHD |
Studies
of Lipid-Lowering Drugs With Type 2 Diabetes Patients: Fibric Acids
Three
large-scale studies with fibric acid drugs have included diabetic patients:
The Helsinki Heart Study, the Veterans Affairs High-Density Lipoprotein
Cholesterol Intervention Trial (VA HIT), and the Diabetes Atherosclerosis
Intervention Study (DAIS).
The
Helsinki Heart Study
This study measured the effect of treatment with gemfibrozil versus
placebo in men with an average total cholesterol level of about 290
mg/dL and a triglyceride level of approximately 175 mg/dl. The study
included 135 patients with type 2 diabetes. An analysis of these patients
found that, compared with the nondiabetic patients, they had lower HDL
levels (P<0.001), higher triglyceride levels (P<0.001), and greater
body mass indices (P<0.001). The incidence of MI and cardiac death was
found to be statistically significantly higher (P<0.02) among diabetic
subjects than among nondiabetic subjects. Lipid changes in the group
of diabetic patients treated with gemfibrozil were similar to those
observed in nondiabetic patients. Cardiac events occurred in 10.5% of
diabetic patients receiving placebo and 3.4% of diabetic patients receiving
gemfibrozil. Although this difference represented a reduction in risk
of 65%, this finding was not statistically significant, probably because
of the small number of subjects with diabetes in the study.
The
Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial
(VA HIT)
Investigators compared gemfibrozil versus placebo in 2531 men with
CHD whose primary lipid abnormality was a low HDL level. The study included
627 subjects with diabetes. In the group of diabetic patients taking
gemfibrozil, there was a statistically significant (P<0.05), 24% reduction
in the risk of death due to CHD, nonfatal MI, and confirmed stroke.
The diabetics in the placebo group had a much higher event rate (36%
in 5 years) compared with the nondiabetics receiving placebo (22%).
Diabetes
Atherosclerosis Intervention Study (DAIS)
This was a 3-year, multinational, angiographic, double-blind, placebo-controlled
study, in which subjects received 200 mg micronized fenofibrate or placebo.
The primary objective was to determine if long-term correction of dyslipoproteinemia
with fenofibrate decreased progression, or caused regression, of preexisting
coronary atherosclerosis. The study included 418 patients with diabetes.
Preliminary results from DAIS were presented at the XIIth International
Symposium on Atherosclerosis in Stockholm, Sweden in June, 2000. The
investigators reported that fenofibrate reduced atherosclerosis by 40%.
There was also a 23% decrease in cardiac death and nonfatal events,
though this secondary endpoint was not statistically significant because
of the small number of patients.
| Study
|
Drug |
No.
of Subjects Diabetic (Total) |
Results
in
Diabetic Subject |
| The Helsinki
Heart Study
(Diabetes Care. 1992;5:820) |
Gemfibrozil |
135
(4081) |
 65%
cardiac events, NS |
| The Veterans
Affairs High-Density Lipoprotein Cholesterol Intervention Trail
(VA HIT)
(N Engel J Med. 1999;341:410.) |
Gemfibrozil |
627
(2531) |
24%
risk of death from CHD, nonfatal MI, and stroke (P<0.05) |
Diabetes Atherosclerosis
Intervention Study (DAIS)
(Presented at the XIIth International Symposium on Atherosclerosis;
June, 2000; Stockholm, Sweden) |
Fenofibrate |
418
(418) |
23%
deaths and cardiac events (preliminary results) , NS |
NS
= No statistically significant
Conclusions
|
Patients with
type 2 diabetes are at increased risk of cardiovascular disease |
|
Diabetics without
prior MI face similar risk of death from CHD as nondiabetics with
prior MI |
|
The risk of
cardiovascular disease is often due to dyslipidemia |
|
Dyslipidemia
should be treated as aggressively as hyperglycemia to reduce the
risk of cardiovascular disease |
References
American Diabetes Association. Diabetes Care. 2000;23(suppl 1);S57-S60.
Garg A. Grundy SM. Diabetes Care. 1990;13:153-169.
Haffner SM, et al. N Engl J Med. 1998;339:229-234.
