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Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes

Carlos Abraira, MD; John Colwell, MD, PhD; Frank Nuttall, MD, PhD; Clark T. Sawin, MD; William Henderson, PhD; John P. Comstock, MD; Nicholas V. Emanuele, MD; Seymour R. Levin, MD; Ivan Pacold, MD; Hae Sook Lee

Arch Intern Med. 1997;157(2):181-188.

Abstract
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 dose 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 any 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.

Arch Intern Med. 1997;157:181-188

Footnotes
The affiliations of the authors appear in the acknowledgment section at the end of this article. A list of the members of the VACSDM Study Group appears on page 184.

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