Glucose metabolism and hyperglycemia

Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA(1c)), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that Hb(A1)c should be < 7%. The measurement of the HbA(1c) concentration is considered the gold standard for assessing long-term glycemia; however, it does not reveal any information on the extent or frequency of blood glucose excursions, but provides an overall mean value only. Postprandial hyperglycemia occurs frequently in patients with diabetes receiving active treatment and can occur even when metabolic control is apparently good. Interventional studies indicate that reducing postmeal glucose excursions is as important as controlling fasting plasma glucose in persons with diabetes and impaired glucose tolerance. Evidence exists for a causal relation between postmeal glucose increases and microvascular and macrovascular outcomes; therefore, it is not surprising that treatment with different compounds that have specific effects on postprandial glucose regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappa B activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA(1c), fasting glucose, and postmeal glucose peak.