Physiological insulin replacement in type 1 diabetes mellitus.

The DCCT and UKPDS studies have definitely established that in type 1 as well as in type 2 diabetes mellitus, long-term near-normoglycaemia strongly protects against onset and/or progression of microangiopathic complications. Therefore, implementation of insulin strategies to maintain long-term near-normoglycaemia is of key importance in the management of diabetes mellitus. To successfully reach the goal of near-normoglycaemia, insulin therapy has to be physiological, i.e. it has to mimic nature by providing a bolus of insulin at meal ingestion, and by replacing the need for basal insulin between meals and during the night. The meal-time insulin needs can be best met by s.c. injection of a short-acting insulin analogue (lispro, aspart). Short-acting insulin analogues should be preferred to human regular insulin for three main reasons. First, convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); second, lower blood glucose 2-hour after meals; third, less risk for late post-prandial hypoglycaemia. However, the benefits of meal-time treatment with short-acting insulin analogues become apparent only by the extent to which replacement of basal insulin is optimised as well. The interprandial (especially nocturnal) need for basal insulin can be best met by the continuous s.c. insulin infusion by an external minipump, the gold standard of basal insulin replacement. Continuous s.c. insulin infusion in the basal state is so good because it uses a short-acting insulin analogue (low variability in s.c. absorption, flat and peak-less action profile), not insulin preparations with retarded action (high variability of s.c. absorption, peak of action) likewise the model of multiple daily insulin injections. A second choice option is s.c. injection of an insulin preparation with retarded action. At present, the long-acting insulin analogue glargine is the retarded insulin preparation of choice because its action profile is flat, peakless and long-lasting (approximately 24 hours). This is in contrast with the peak action profile of NPH insulin which exhibits a short duration of action (10-15 h). Thus, the modern insulin strategies for intensive therapy always include use of a short-acting insulin analogue at meal-time, and use of either continuous s.c. insulin infusion, or a s.c. injection of insulin glargine to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of continuous s.c. insulin infusion, and should always be preferred to NPH in all insulin-requiring diabetic patients, both type 1 and type 2.