Given that cardiovascular disease is a common complication of diabetes (1) and the leading cause of death among people with diabetes (2,3), it is important that we use the most effective therapies to manage lipids, blood pressure, and glycemia to reduce the risk, progression, and impact of macrovascular disease. Recent studies by Gaede et al. (4) clearly demonstrated that intensive management of all risk factors, including lipids, blood pressure, and glycemia, had significant beneficial effects on cardiovascular-related deaths. This intensive therapy was also found to be cost-effective (5). Nevertheless, questions are now being raised regarding the importance of glycemia relevant to the prevention and/or progression of cardiovascular disease. To begin answering these questions, we first need to ask: Is there any reason not to believe there is a link between hyperglycemia and cardiovascular disease? We have strong evidence from large randomized controlled trials that clearly establish a causal relationship between poor glycemic control and the development of microvascular disease (6,7). Why should we assume that large blood vessels are immune to the same damaging effect of hyperglycemia? We should not: there is plenty of evidence linking hyperglycemia to macrovascular risk. Analysis of data from 3,642 U.K. Prospective Diabetes Study subjects (for whom complete data for potential confounders were available) showed a significant 14% ( P < 0.0001) reduction in myocardial infarction for each 1% reduction in mean A1C (8). An early meta-regression analysis by Coutinho et al. (9) showed that the progressive relationship between glucose levels and cardiovascular …