A major therapeutic question in considering accelerated atherogenesis in patients with type 2 diabetes mellitus is whether reducing insulin resistance, as a proximal defect of a host of proatherogenic abnormalities including hyperglycemia, will be superior for decreasing mortality and coronary artery disease (CAD) risk compared with treating hyperglycemia to overcome insulin resistance with insulin-providing agents. This question is highly relevant, since earlier targeted glycemic control trials utilizing conventional glucose-lowering strategies that increase insulin levels have generally failed to reduce CAD risk despite markedly reducing microvascular risk. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial seeks to determine whether primarily using an insulin-sensitizing strategy for treatment of type 2 diabetes is superior when compared with primarily using an insulin-providing strategy with regard to cardiovascular outcomes. This article presents the rationale, design, and methods being used to test the glycemic control hypothesis in BARI 2D.
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