Cardiovascular events and correlates in the Veterans Affairs diabetes feasibility trial: Veterans Affairs cooperative study on glycemic control and complications in type II diabetes

Background: The risks and benefits of intensive therapy in non-insulin- dependent diabetes mellitus (NIDDM) need to be defined. In preparation for a long-term trial, a feasibility study of 153 men in 5 medical centers compared standard vs intensive insulin therapy. Objective: To assess the rate of development of new cardiovascular events and their correlates. Methods: Patients with a mean±SD age of 60±6 years and diagnosis of NIDDM for 7.8±4.0 years were randomly assigned to a standard (1 insulin injection every morning) or to an intensive treatment arm (stepped plan from 1 evening injection of insulin, alone or with glipizide, to multiple daily injections) designed to attain near normal glycemia levels. A 2.07% separation of glycosylated hemoglobin (HbA(1c)) was sustained for a mean follow-up of 27 months (P<.001). Predefined cardiovascular events were assessed by a committee unaware of treatment assignment. Results: Mild and moderate hypoglycemic events were more frequent in the intensive than in the standard treatment arm (16.5 vs 1.5 per patient per year, respectively). Mean insulin close was 23% lower in the standard treatment arm (P<.001). There were 61 new cardiovascular events in 24 patients (32%) in the intensive treatment arm and in 16 patients (20%) in the standard treatment arm (P=.10). There was no difference in total and cardiovascular mortality (n=5 and n=3 in the intensive and standard treatment arms, respectively) or in new events in patients with cardiovascular history (n=10 in each arm). In Cox regression analysis, the only significant correlate for new cardiovascular events was previous cardiovascular disease (P=.04). Entering in the analysis airy baseline cardiovascular abnormality, the regression model indicated a lower HbA(1c), level prior to the event as the only correlate for new cardiovascular events (P=.05). Conclusion: A long-term prospective trial is needed to assess the risk-benefit ratio of intensive insulin therapy for NIDDM in patients who require it.