Clinical strategies for controlling peaks and valleys: type 1 diabetes.

The DCCT and UKPDS have established that in type 1 and in type 2 diabetes respectively, long-term near-normoglycaemia protects against the onset and/or progression of microangiopathic complications. Therefore, insulin strategies to maintain long-term near-normoglycaemia are of key importance in the management of diabetes. To successfully achieve near-normoglycaemia, insulin therapy must mimic nature by providing a bolus of insulin at meal ingestion and by replacing basal insulin between meals and overnight Mealtime insulin needs can be best met by subcutaneous (s.c.) injection of a rapid-acting insulin analogue such as insulin lispro or insulin aspart. Rapid-acting insulin analogues are preferred to human regular insulin for three reasons: convenience (meal-time injection, better adaptation of insulin dose to carbohydrate content of the meal); lower blood glucose 2 hours after meals; and less risk for late postprandial hypoglycaemia. However, in type 1 diabetes the benefits of mealtime treatment with rapid-acting insulin analogues become apparent only to the extent that replacement of basal insulin is optimised. The interprandial need for basal insulin can be best met by continuous s.c. insulin infusion (CSII). CSII is very good for basal insulin replacement because it uses a rapid-acting insulin analogue with low variability in s.c. absorption, resulting in a flat and peakless action profile. A second option for basal insulin replacement is s.c. injection of an insulin preparation with retarded action. The two most commonly used are NPH and insulin glargine. NPH exhibits an action profile with a peak 4 to 5 hours after injection and duration of action of 10 to 15 hours. Insulin glargine has a peakless action profile and lasts approximately 24 hours. To optimise replacement of basal insulin with NPH, a few units of NPH must be combined with rapid-acting analogues at meals and also given at bedtime (0.2 U/kg). With insulin glargine, 0.2 to 0.4 U/kg should be injected once or, in some patients, twice daily. Modern insulin strategies for intensive therapy should include use of a rapid-acting insulin analogue at meal-time, and use of CSII to replace basal insulin. Insulin glargine reproduces closely the pharmacokinetics and pharmacodynamics of CSII and should be considered for substitution of basal insulin, especially in type 1 diabetes.