Abstract
The hallmark study in type 1 diabetes (T1D), the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC), demonstrated a significant reduction in micro- and macrovascular complications with improving glucose control in the intensively treated arm. 4 Similarly, the United Kingdom Prospective Diabetes Study (UKPDS) in type 2 diabetes (T2D) showed a 16% reduction in CVD (combined fatal or nonfatal myocardial infarction [MI] and sudden death) with improved glucose control. 5 This topic is further discussed in this issue by Home 6 in his article regarding CVD and oral glucose-lowering therapies in T2D. Additional analysis of the UKPDS showed that every 1% A1c reduction was related to a decrease in cardiovascular complications. 7
The American Diabetes Association (ADA) recognizes that subjects with diabetes are at high risk for CVD and recommends patients achieve a glycosylated hemoglobin (A1c) level of <7.0%, blood pressure of <130/80 mm Hg, and low-density lipoprotein level of <100 mg/dL (“ABCs of diabetes management). Despite these targets, only 13.2% of patients with diabetes reached all three goals. 8 Further discussion on glycemic and non-glycemic targets is presented by Hirsch and O'Brien 9 in this supplement.
During the last three decades multiple studies have focused on relationships between intensive diabetes management and the reduction of associated complications. The EDIC extension of the DCCT demonstrated that lowering A1c reduces macrovascular complications, such as CVD and strokes. In fact, it was found that intensive insulin treatment reduced the risk of cardiovascular events by 42%. Furthermore, nonfatal MI, stroke, and death from CVD were reduced by 57%. 10 However, a more recent study, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), in T2D was prematurely halted because of a 20% increase in mortality among subjects who were treated intensively (A1c targets <6%). 11 There was a threefold increase in severe hypoglycemia and a significant weight gain in subjects participating in the intensive treatment arm. The relationships among hypoglycemia, diabetes, and CVD are further discussed by Snell-Bergeon and Wadwa. 12 Exploratory analyses of the ACCORD database were unable to explain or identify the reason for excess mortality (evaluating variables such as weight gain, hypoglycemia, drugs, or drug combinations). Similarly, two other recent trials, the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) 13 and the Veterans Affairs Diabetes Trial (VADT), 14 showed no reduction in cardiovascular outcomes with intensive glycemic control.
The best way to reduce CVD in diabetes may to be to detect the disease early (anatomically using computerized tomography angiography or magnetic resonance angiography) and developing new biomarkers. The role of glycocalyx and other biomarkers is discussed in this supplement by Lemkes et al. 15
Over the past two decades 80% of CVD and diabetes mortality has occurred in low- and middle-income countries, leading to a significant public health threat. The reasons for increase in CVD among emerging economies might include urbanization, genetic and environmental factors, and other lifestyle changes as discussed at length by Pradeepa et al. 16 in this supplement. Better methods are needed to identify CVD risk in different populations throughout the world.
The recent introduction of incretin therapy for management of T2D has been shown to have pleiotropic effects on coronary endothelium as described by Lebovitz and Banerji 17 in this supplement. The use of glucagon-like polypeptide-1 analogs and dipeptidyl peptidase-4 inhibitors primarily focuses on the paradoxical postprandial rise in glucagon (via rise in glucagon-like polypeptide) and insulin resistance.
Although it is not yet confirmed, there is a growing consensus that CVD might begin at a younger age in T1D patients. Truong et al. 18 provide an excellent overview of this topic in the current supplement. It is not known if early medical intervention at the stage of dysglycemia (impaired glucose tolerance) will eventually prevent significant CVD, and this has been evaluated by the recently concluded Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. The data from this trial will be presented in June 2012 at the 72nd Scientific Sessions of the Annual American Diabetes Association in Philadelphia, PA.
Prevalence, cost, CVD, and mortality in subjects with diabetes have significantly increased worldwide. Improvement in glucose control as well as reduction in blood pressure and low-density lipoprotein to near-normal levels should be the goal for patients with diabetes. Early detection of CVD by biological markers and newer imaging modalities is needed to reduce CVD in patients with diabetes.
We would like to sincerely thank all of the authors for their hard work and contributions to this supplement. Their time and dedication have made this supplement possible, and we hope that you enjoy their outstanding work.