Glucose Control and Cardiovascular Disease

There is a substantial amount of clinical data showing the relationship between diabetes and atherosclerosis and its clinical complications (1,2). Cardiovascular disease (CVD) is more common in people with diabetes than in subjects without the disease, and when it is present, it also has a more aggressive course and a worse prognosis (3). The bulk of epidemiological data has firmly established that type 2 diabetes is associated with more than a twofold increased risk for cardiovascular (CV) death. In the case of subjects with type 1 diabetes, in spite of the fact that the CVD rate is significantly lower compared with the population with type 2 diabetes, their relative risk for coronary heart mortality is sevenfold higher than in matched counterparts without the disease (4). Despite all of these data concerning the association of diabetes and CVD, the exact mechanism by which diabetes, and its alterations, is linked to atherosclerosis remains incompletely elucidated. This is especially true in the case of hyperglycemia. The role of nonglycemic factors that accompany the vast majority of patients with type 2 diabetes, such as high blood pressure, dyslipidemia, and hemorreological abnormalities, among others, is much better understood and seems to be independent of glycemia. In addition to this, there have been studies demonstrating that interventions addressed to control these other factors in patients with diabetes effectively reduce CV risk. There also have been data including the use of statins, aspirin, the aggressive management of hypertension, and the use of ACE inhibitors (5,6). Therefore, the positive effects that the control of other factors beyond hyperglycemia exert on CVD are, nowadays, unquestionable. In contrast, to date, the positive effect of intensive glucose management in comparison to nonintensive glucose control on CVD outcomes is still far from proven and seems unlikely to change in the near future (7). As an example, the American Diabetes Association/ American Heart Association in their last joint scientific statement on primary prevention of CVD in people with diabetes declared that, “No clinical trials of a glycemic intervention have provided clearcut evidence that glucose lowering reduces the risk of CVD in subjects with diabetes” (8). Furthermore, one of the latest U.S. Food and Drug Administration announcements on antidiabetic agents clearly concluded that, “There is insufficient information available to determine whether any oral antidiabetic medicine reduces cardiovascular risk” in people affected by diabetes.