Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era.

In physiology, insulin is released continuously by the pancreas at a nearly constant rate between meals and in the fasting state (basal insulin secretion). The pivotal role of basal insulin is to restrain release of glucose from the liver and free fatty acids from adipose tissue, thus preventing hyperglycemia and ketosis. In type 1 diabetes mellitus (T1DM) (absolute insulin deficiency), the replacement of basal insulin is challenging because the currently available pharmacological preparations of long-acting insulin do not exactly reproduce the fine physiology of flat action profile of basal insulin of subjects without diabetes. NPH and NPH-based insulin mixtures no longer have a place in the treatment of T1DM because of their early peak effects and relatively short duration of action, which result into risk of nocturnal hypoglycemia and fasting hyperglycemia, respectively, after the evening injection. Only continuous subcutaneous (s.c.) insulin infusion (CSII) or long-acting analogs such as glargine (>24 h in duration, once a day) and detemir (<24 h in duration, once or more often twice a day) should be used as basal insulin in T1DM in combination with mealtime rapid-acting analogs. CSII and the long-acting analogs are nearly peakless and therefore reduce the risk for hypoglycemia (especially at night), blood glucose (BG) variability, and lower A1C with similar or less hypoglycemia. CSII is the "gold standard" of replacement of basal insulin because of better reproducibility of subcutaneous absorption of soluble insulin. Although CSII is not superior to multiple daily insulin injections in the general T1DM population, CSII might be indicated in subsets of T1DM (long-term T1DM with insulin "supersensitivity" and needs for low-dose insulin, some individuals with variable subcutaneous absorption of long-acting analogs) to minimize BG variability, reduce hypoglycemia, and benefit A1C.