Treatment of patients with severe insulin deficiency; what we have learned over the past 2 years.

The initial injection in 1922 of a pancreatic extract, or insulin as it came to be known, into a patient with diabetes mellitus has since been followed by the successive introduction of longer-acting insulins, more highly purified insulins, and insulins that have been modified to more closely match insulin activity to patients' physiologic requirements. The recently introduced rapid-acting insulin analogues lispro and aspart and the long-acting analogue glargine are further refinements of insulin therapy. Current treatment strategies for severe insulin deficiency are based on the need to provide 2 components of insulin replacement: basal and postprandial. Rapid-acting insulin has been shown to provide superior postprandial glucose control compared with regular insulin. Truly effective control of basal insulin has been achieved by the introduction of the insulin pump in the 1980s and insulin glargine in 2001. Insulin glargine is the first insulin analogue to provide, in a majority of patients, a continuous level of insulin without a pronounced peak after a single daily injection, closely mimicking the normal pancreatic release of basal insulin in healthy individuals. Clinical experience is providing many insights into how basal and prandial components of insulin therapy can be best combined, although evidence from controlled trials will take some years to accumulate. Experience and observations since 2001 indicate that insulin therapy should be introduced earlier in patients with type 2 diabetes to control blood glucose levels. More importantly, the greatest benefit of insulin glargine has been to change positively the way physicians and patients think about insulin therapy. Newer insulin analogues, improved devices for home glucose monitoring, and pulmonary inhaled insulin are other innovations that promise improvement of hemoglobin A(1c) levels.