Glycemic Control and Reduction of Cardiovascular Risk

Supported by an unrestricted educational grant from Aventis, Inc.

Thursday, June 17, 2004
6:00-8:30 AM

Program Director:
Jerry Palmer, MD

Faculty:
Andrew Selwyn, MD
Martin Abrahamson, MD

Reviewed by Joelle Escoffery, PhD

The goals of this symposium were to examine the available clinical evidence related to tight glycemic control and reduction of cardiovascular risk, and to evaluate therapeutic options for patients with type 2 diabetes. The increasing incidence and prevalence of type 2 diabetes has created a considerable burden both in terms of mortality and morbidity and in terms of direct and indirect financial costs. Type 2 diabetes is considered a cardiovascular equivalent, and increasing the number of cardiovascular risk factors has a greater effect on the likelihood of cardiovascular death among people with diabetes, as compared with people who do not have diabetes. Impaired glucose tolerance is also considered a risk factor for the development of cardiovascular disease. Further, insulin resistance is associated with disordered fat metabolism, and the atherogenic dyslipidemia often seen among people with type 2 diabetes has been shown to affect the progression of coronary artery disease. A number of studies have demonstrated the link between glycemic and other risk factor control and cardiovascular outcomes among people with diabetes. In the Diabetes Control and Complications Trial (DCCT), intensive treatment of type 1 diabetes was associated with a decrease in albuminuria, improved endothelial functioning, reduced carotid intima media thickness, and a nonsignificant trend for a reduction in cardiovascular events. The Hypertension Optimal Treatment (HOT) study demonstrated a 67% reduction in cardiovascular risk among diabetic patients when diastolic blood pressure was reduced to 80 or lower. A number of studies have demonstrated that reducing low-density lipoprotein (LDL) cholesterol is associated with a reduction in cardiovascular events among people with diabetes. Thus, aggressive treatment of both diabetes and its risk factors was advocated.

Because type 2 diabetes is a progressive disorder and because of the lengthy delay between the onset of metabolic disturbances and diagnosis of type 2 diabetes, patients have typically lost approximately 50% of β-cell function by the time of diagnosis. Further, in the United Kingdom Prospective Diabetes Study (UKPDS), over 70% of patients were unable to meet the A1C goal of 7% with lifestyle or monotherapy. Further, recent data suggest that 63% of patients with diabetes fail to meet the American Diabetes Association’s A1C goal of 7%. Accordingly, the following strategies were suggested for improvement in the achievement of treatment goals: 1) earlier diagnosis and treatment so that there is grater preservation in β-cell function at the time of diagnosis, 2) matching the pharmacology with the pathophysiology, 3) earlier use of combination therapy, and 4) more aggressive management of results of blood glucose data. A number of studies have demonstrated that using combination therapy results in greater decreases in A1C with smaller doses. Further, several classes of oral medications have been shown to have specific cardiovascular benefits.  Metformin has been associated with a 39% reduction in myocardial infarction. The thiazolidinedione (TZDs) have beneficial effects on lipids, PAI-1, C-reactive protein, and adiponectin.  Finally, a number of treatment options may play a role in preserving β-cell function, including the TZDs, earlier use of insulin therapy, and the emerging GLP-1 agonist exenatide.