Managing Cardiovascular Disease in Type 2 Diabetes

Summarized by Robert W. Griffith, MD
February 7, 2003

Introduction

Cardiovascular mortality is twice as high in diabetic men as in non-diabetics. Survival after myocardial infarction is worse in diabetic men and women; in men, the death rate in diabetics is equal to that in non-diabetics who have already had an infarct. It's therefore very important to lower the number of undiagnosed diabetics, and to manage the risk factors for cardiovascular disease in known diabetics. Dr Arshag Mooradian has written a concise summary of present thinking on this subject, and we summarize the main findings here. The recognized risk factors are more prevalent in diabetics, and they are associated with accelerated atherosclerosis.

Lifestyle

Modest calorie restriction and increased physical activity, leading to some degree of weight loss, have been shown to delay the onset of diabetes significantly. Two anti-obesity drugs (sibutramine and orlistat) that are approved for weight loss can also improve cardiovascular risk factors. Obviously, smoking and excessive alcohol intake should be forbidden, although 1-2 drinks a day may reduce the risk of diabetes as well as of cardiovascular death.

Hyperglycemia

Tight control of hyperglycemia leads to a reduction in glycosylated hemoglobin (HbA1c), which is generally regarded as being the target parameter for treatment. There is a continuous relationship between all-cause mortality and HbA1c levels. Thus management should try for HbA1c levels as low as possible consistent with avoiding hypoglycemia. The HbA1c goal recommended by the American Diabetic Association is 7%, while the American College of Endocrinologists and the European Diabetes Policy Group recommend a target of 6.5%.

Postprandial hyperglycemia may be a separate problem. A consensus is emerging that 1-hour postprandial levels should be below 160 mg/dL (8.9 mmol/L), and 2-hour levels below 140 mg/dL (7.8 mmol/L).

The author provides a suggested algorithm for drug therapy, which is reproduced in the following table:

Dyslipidemia in diabetes

The prevalence of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels in diabetics is twice that in non-diabetic subjects, so these lipids should receive special attention. The baseline lipid level should be established after 6-12 weeks of intense lifestyle measures. If the serum triglyceride is over 500 mg/dL (5.6 mmol/L), fibrates are the first choice of therapy. At follow-up, if the low-density lipoprotein cholesterol (LDL-C) is over 130 mg/dL (3.4 mmol/L), a statin, or niacin, is added. On the other hand, if the baseline LDL-C is over 130 mg/dL and the triglyceride below 500 mg/dL, a statin should be used first; a fibrate or niacin can be added later if the triglyceride is above 200 mg/dL.

The recommended goal for LDL-C in diabetic patients is less than 100 mg/dL (2.6 mmol/L), that for triglyceride below 150 mg/dL (1.7 mmol/L), while HDL-C should be above 40 mg/dL (1.0 mmol/L).

Hypertension in diabetes

Less than 1/3 of treated hypertensives have their blood pressure adequately controlled, whereas it's been shown that the risk of myocardial infarction in diabetics correlates with their blood pressure levels. In the United Kingdom Prospective Diabetes Study, a modest reduction of blood pressure in the intensively treated subjects (a mean of 144/82 mm Hg, vs. 154/87 mm Hg in controls) reduced the risk of diabetes-related death by 32%, that of stroke by 44%, and that of congestive heart failure by 56%. Effective control of isolated systolic hypertension in diabetics is also associated with an equal or greater reduction in cardiovascular events as that achieved in non-diabetics.

The desired goal of blood pressure control should be 130/80 mm Hg. The author recommends an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) as the first line of treatment if nephropathy is present. In patients with established cardiovascular disease, beta-blockers are advocated.

The recent ALLHAT study, in which 36% of the subjects were diabetic, showed long-term benefits of treating hypertension with diuretics rather than ACE inhibitors or beta-blockers.¹ While results were similar for the diabetic subgroup as for the whole population, detailed analyses of the diabetics in the study remain to be reported.

Other considerations

Platelet aggregability is increased in diabetes, and fibrinolytic capacity is reduced. Consequently, antiplatelet therapy (aspirin or clopidogrel) reduces cardiovascular risk, and is often recommended. A daily aspirin (81 mg) is the simplest approach, but if there are any problems, or a cardiovascular event occurs, clopidrogel should be substituted.

Dietary supplements are mentioned briefly in this review. There is no good clinical evidence that antioxidants, including vitamins A, C, and E, have the ability to reduce cardiovascular risk in diabetic subjects.

In recent years, new risk factors for cardiovascular disease have emerged. In diabetics, microalbuminuria is one such factor. The beneficial effects of ACE inhibitors and ARBs in this condition are well established. Diabetics tend to have higher C-reactive protein (CRP) levels than non-diabetics, suggesting the increased role of inflammation in the accelerated atherosclerosis seen in diabetes. And plasma homocysteine levels are associated with cardiovascular disease in diabetic and non-diabetic people; this supports the need to ensure adequate folic acid intake, if necessary by the use of supplements.

Comment

While diabetes is increasing worldwide, so is our ability to combat many of it's effects. Apart from major changes in lifestyle (weight control, exercise, not smoking), tight control of blood pressure is probably the most cost-effective measure to reduce deaths and morbidity. Better education of patients - about the risks and what to do - and physicians - about the need for tight control of glucose, blood pressure, and lipid levels - should ensure that we can reduce the long-term effects of this disease.

Source

• Cardiovascular disease in type 2 diabetes mellitus. Current management guidelines. AD. Mooradian, Arch Intern med, 2003, vol. 163, pp. 33--40

Footnotes
1. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Study Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-2997

Related Links
Older Adults Need Better Treatment of Cardiovascular Risk Factors
Exercise Helps Control Diabetic Vascular Disease
Angiotensin-Receptor Antagonists in Type 2 Diabetes
ACE Inhibitor Beneficial in Diabetics at Risk

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