Elsevier

Mayo Clinic Proceedings

Volume 74, Issue 2, February 1999, Pages 171-180
Mayo Clinic Proceedings

Review
Improving the Adverse Cardiovascular Prognosis of Type 2 Diabetes

https://doi.org/10.4065/74.2.171Get rights and content

Approximately 80% of all patients with diabetes die of cardiovascular disease. The traditional management of type 2 diabetes has been ineffective in altering this dismal prognosis. Insulin resistance is the fundamental defect of type 2 diabetes. Insulin resistance often leads to hyperinsulinemia, which is associated with hypertension, atherogenic dyslipidemia, left ventricular hypertrophy, impaired fibrinolysis, visceral obesity, and sedentary lifestyle. Although all these conditions are associated with atherosclerosis and adverse cardiovascular events, the therapeutic efforts in patients with diabetes have focused predominantly on normalizing glucose levels. Improved insulin sensitivity through lifestyle modifications or pharmacologic therapy (troglitazone and metformin) will lower both insulin and glucose levels as well as diminish dyslipidemia and hypertension. In contrast, sulfonylurea agents lower glucose by increasing insulin levels and may increase the risk of cardiovascular events. Therapy including aspirin, lipid agents (for example, statins), angiotensin-converting enzyme inhibitors, β-adrenergic blockers, postmenopausal estrogen replacement, and vitamin E should be considered for patients with type 2 diabetes. In most patients with diabetes who have multivessel coronary artery disease, coronary artery bypass grafting is superior to coronary angioplasty for improving long-term cardiovascular prognosis. This superiority is mediated in part by the use of a left internal mammary graft to the left anterior descending coronary artery. Urgent coronary angioplasty or thrombolytic therapy should be considered for all patients with diabetes who have acute myocardial infarction.

Section snippets

INSULIN RESISTANCE/HYPERINSULINEMIA

Insulin resistance is a state whereby tissues such as skeletal muscle have a reduced sensitivity to the effects of insulinstimulated glucose uptake. This impairment leads to hyperinsulinemia, which sometimes evolves into overt type 2 diabetes mellitus.4, 5 Diabetes is strongly correlated with CAD, but, surprisingly, the duration of diabetes bears little or no relationship to the risk of clinically apparent CAD.6, 7, 8 This situation is likely due to the fact that insulin

Sulfonylureas

Until approximately 2 years ago, sulfonylureas were the only option available in the United States for the oral treatment of diabetes. Concerns about the safety of this class of drugs date back almost 3 decades to the University Group Diabetes Program.15 This prospective, randomized trial found that patients with diabetes who were treated with tolbutamide rather than placebo experienced a significantly increased cardiovascular mortality rate. Because of the criticisms of the methods of that

DYSLIPIDEMIA

Both type 2 diabetes mellitus and insulin resistance typically are associated with atherogenic dyslipidemia. This dyslipidemia (characterized by increased trigIycerides, depressed HDL, and LDL levels that are normal to moderately increased) is difficult to treat and is associated with a worse prognosis than is an isolated increased LDL level44 (which is, in contrast, relatively easy to treat). Lifestyle modification involving daily vigorous exercise of 30 minutes or more with both aerobic and

HYPERTENSION

Type 2 diabetes mellitus is commonly associated with hypertension. This association is probably mediated through shared causal factors such as insulin resistance, obesity, sedentary lifestyle, and maladaptive diet. In patients with diabetes, hypertension, even when mild, significantly magnifies the risk of coronary heart disease, stroke, peripheral vascular disease, and renal failure.61 Aggressive treatment of increased blood pressure levels improves prognosis in these patients, particularly if

ANTIOXIDANTS

Because patients with diabetes tend to have easily oxidized (small and dense) LDL particles, antioxidant therapy may be especially important for preventing cardiovascular events in these patients. Although not definitive, a randomized trial of 2,002 patients with CAD suggested that vitamin E reduced the risk of nonfatal myocardial infarction.73 In light of these findings, a prudent approach would be to use vitamin E at doses of approximately 400 IU/day for patients with diabetes. Insufficient

ASPIRIN

The term “atherothrornbosis” has been used to describe the pathogenic events leading to CAD. Impaired fibrinolysis has a role in acute and chronic manifestations of CAD. Insulin resistance and atherogenic dyslipidemia are associated with impaired fibrinolysis due in part to increased plasminogen activator inhibitor-1 levels.74 Aspirin helps to prevent acute coronary events by reducing platelet-thrombus formation at the site of a ruptured plaque.75 Because about 80% of patients with diabetes

ESTROGEN

Estrogen replacement therapy for postmenopausal women increases HDL levels, reduces LDL levels, has antioxidant activity, and improves insulin sensitivity.79 Estrogen replacement therapy is associated with reductions in cardiovascular mortality of up to 50% in postmenopausal women.80 These relative risk reductions are similar for diabetic and nondiabetic cohorts of women.81, 82 however, because absolute rates of myocardial infarction and cardiovascular death are much higher for women with

ACUTE MYOCARDIAL INFARCTION

In the setting of acute myocardial infarction, the presence of diabetes is an independent correlate of increased early and late mortality rates, with a relative risk of approximately 2.0 in comparison with the nondiabetic cohort.27 Patients with diabetes tend to seek medical attention later in the course of the infarction, are usually older, and are more likely to be women. In addition, patients with diabetes have a high incidence of multivessel coronary disease and left ventricular dysfunction.

CORONARY REVASCULARIZATION

In patients with diabetes, the long-term prognosis is worse than that in nondiabetic patients after either coronary artery bypass grafting (CABG)87 or coronary angioplasty (PTCA).88 In the Bypass Angioplasty Revascularization Investigation (BARI), among the diabetic subgroup of 350 patients, the 5-year survival rate was significantly better after CABG (81%) than after PTCA (65%; P = 0.003).89 This advantage conferred by CABG was primarily dependent on the use of a left internal mammary graft

Acknowledgment

We thank Lori L. Maher for her expertise in preparation of the submitted manuscript.

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    Copyright © 1999 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.