Shifting the disease management paradigm from glucose: what are the pros?

With the worldwide growing prevalence of obesity and type 2 diabetes, cardiovascular disease (CVD), diabetic nephropathy, retinopathy, and neuropathy as principal complications of diabetes are expected to become a major public health challenge. Diabetes accounts for at least double the number of death rates compared with otherwise healthy individuals. Hyperglycemia represents the hallmark of diabetic metabolic changes, but whether antihyperglycemic treatment alone is sufficient to prevent cardiovascular and other organic complications in type 2 diabetes is a matter of debate. A recent meta-analysis of epidemiological studies reported an 18% increase in CVD risk for every 1% increase in A1C (1). Two major studies have underlined the importance of optimal glycemic control in reducing diabetes-related complications. The U.K. Prospective Diabetes Study (UKPDS) showed that intensive glycemic control (mean A1C below 7%) by means of insulin or oral agents in type 2 diabetic patients reduces the relative risk for microvascular outcomes by 25% over a period of 10 years (relative risk reduction). The reduction in macrovascular end points (myocardial infarction) was of borderline significance (16% relative risk reduction, P = 0.052) (2). The Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) trial reported a 50% reduction in CVD outcomes in type 1 diabetic patients treated intensively over a period of 6.5 years and followed for a further 12 years (3). In contrast to these data, the intensive glucose-lowering arm of the Action to Control Cardiovascular Risk (ACCORD) trial—a major trial in type 2 diabetic patients—has been recently stopped because of increased mortality in this group (4). The ACCORD trial was set up to test three complementary medical treatment strategies for type 2 diabetes to reduce CVD morbidity and mortality. Aggressive reduction of A1C below 6%, combined increase in HDL cholesterol, and reduction of LDL cholesterol and lowering of blood …