Type 1 diabetes mellitus: effective insulin strategies with less hypoglycemia

Stringent glycemic control is important for preventing the development or progression of complications in type 1 diabetes. This goal may best be achieved by intensive insulin replacement therapy that closely follows the physiologic patterns of secretion observed in patients without diabetes. Premixed insulin formulations of human regular and NPH insulin are commonly used to control blood glucose levels throughout the day, but because these preparations do not mimic the physiologic profile of insulin release, hypo- and hyperglycemia may ensue. Using human regular insulin to control mealtime hyperglycemia is similarly problematic, and thus recently developed rapid-acting insulin analogues, such as lispro and aspart, are now preferred for prandial glucose control. In addition, regimens that combine insulins--eg, NPH insulin for meeting the demand for round-the-clock basal insulin secretion and a rapid-acting insulin analogue to cover mealtime insulin requirements--improve glycemic control, but increase risk of nocturnal hypoglycemia. The ideal basal insulin replacement should feature a uniform continuous release of insulin with a long duration to minimize hypoglycemia. Although such a profile may be achieved with a continuous subcutaneous insulin infusion, new basal insulin analogues, such as once daily, 24-hour insulin glargine, combined with mealtime lispro or aspart, offer comparable glycemic control without the drawbacks of insulin pump use in type 1 diabetes. Insulin glargine reduces the frequency of nocturnal hypoglycemia compared with NPH when used with rapid-acting analogues and thus facilitates optimal insulin replacement therapy.