USE OF THE SHORT-ACTING INSULIN ANALOG LISPRO IN INTENSIVE TREATMENT OF TYPE-1 DIABETES-MELLITUS - IMPORTANCE OF APPROPRIATE REPLACEMENT OFBASAL INSULIN AND TIME-INTERVAL INJECTION-MEAL

To establish whether lispro may be a suitable short-acting insulin pre paration for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conven tional insulins, 69 patients on intensive therapy (4 daily s.c. insuli n injections, soluble at each meal, NPH at bedtime, HbA(1c) <7.5 %) we re studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA(1c) and frequency of hypoglycaemi a were assessed under four different conditions (Groups I-IV). Lispro was always injected at mealtime, soluble 10-40 min prior to meals (wit h the exception of Group IV). Bedtime NPH was continued with both trea tments. When lispro replaced soluble with no increase in number of dai ly NPH injections (Group I, n = 15), HbA(1c) was no different (p = NS) , but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3-4 times daily, lispro (Group II, n = 18), but not soluble (Gro up III, n = 12) decreased HbA(1c) by 0.35 +/- 0.25 % with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA(1c) incr eased by 0.18 +/- 0.15% and hypoglycaemia was more frequent than when soluble was injected 10-40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lisp ro is superior to soluble in terms of reduction of % HbA(1c) and frequ ency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin. (C) 1998 Jo hn Wiley & Sons, Ltd.