Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes

Abstract

Conclusion: In patients with previously poorly controlled type 2 diabetes, use of intensive glucose control vs standard glucose control did not affect rates of major cardiovascular events, death, or microvascular complications. Summary: The authors sought to determine the effects of intensive glucose control on cardiovascular events in patients with longstanding type 2 diabetes. There were 1791 veterans (mean age, 60.4 years), all of whom had suboptimal response to therapy for type 2 diabetes, randomized to either standard or intensive glucose control. All other cardiovascular risk factors were treated the same in both groups. The diagnosis of diabetes was present for a mean of 11.5 years, and 40% had sustained a previous cardiovascular event. An absolute reduction of 1.5 percentage points in the hemoglobin A1C level was the goal for the intensive therapy group compared with the standard therapy group. Primary outcome was time from randomization to the occurrence of the first major cardiovascular event, defined as composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery, or intervention for vascular or coronary disease, and amputation for ischemic gangrene. Median follow-up was 5.6 years. Median hemoglobin A1C was 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (0.88; 95% confidence interval [CI], 0.74-1.05; P = .14). Between the two groups, there were no differences in the occurrence of any components of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81-1.42; P = .62). There was also no difference in microvascular complications between the two groups. Adverse events, predominantly hypoglycemia, occurred in 17.6% of the standard-therapy and 24.1% in the intensive-therapy groups respectively. Comment: Many interventions can affect prognosis in patients with type 2 diabetes, including lifestyle changes, control of blood pressure and lipids, and use of antiplatelet agents. Blood pressure control appears to have better benefit than glucose control (BMJ 1998;317:703-13). Previously, there had been mixed results about whether glucose control can independently reduce cardiovascular complications in patients with advanced type 2 diabetes. The UK Prospective Diabetes Study (BMJ 1998;317:703-13), the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Trial (N Engl J Med 2008;358:2560-72), and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial (N Engl J Med 2008;358:2545-59) all studied the effects of intensive glucose control in patients with diabetes. None of these studies, and now the current study, provided significant evidence for favorable effects of intensive glucose control in controlling cardiovascular events in patients with diabetes. Some, in fact, even suggested harm from this approach. At this point we can say that intensive glucose control early in the course of patients with diabetes may be of benefit; however, in patients with well-established diabetes, it appears that management of other cardiovascular risk factors, such as hypertension and increased lipids, is a more effective approach to preventing cardiovascular morbidity and mortality than tight glucose control.