Hypoglycemia as a barrier to glycemic control.

Diabetes mellitus is associated with significant morbidity and mortality derived from long-term microvascular and macrovascular complications of chronic hyperglycemia. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) have clearly shown the benefits of intensive glycemic control for preventing or delaying the development and progression of long-term complications. However, intensive glycemic control, particularly with insulin therapy, is associated with an increased incidence of hypoglycemia, which is the major barrier to the implementation of intensive treatment from the physician's and patient's perspective. Avoiding the use of intensive treatment most often precludes optimal glycemic control. Some of the many underlying causes of hypoglycemia are defective and deficient counterregulatory responses, relative hyperinsulinization owing to a missed meal, excessive or unplanned exercise, erroneous insulin dosages, excessive insulinotropic effects of some oral secretagogues, and the failure of traditional insulin preparations to simulate the physiologic patterns of endogenous basal insulin secretion found in nondiabetic individuals. Additionally, patient involvement is critical to intensive glycemic control and should involve frequent self-monitoring of blood glucose (SMBG), adherence to treatment regimens, and knowledge of the interrelationship among physical activity, diet, and insulin. This review summarizes the current knowledge on hypoglycemia with a focus on the improvements in insulin therapy (i.e., the mealtime and basal insulin analogs) that may produce more normal physiologic insulin profiles with an attendant lower risk of hypoglycemia than that currently seen in clinical practice.