Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus G. A. Brunner*, S. Hirschberger², G. Sendlhofer*, A. Wutte*, M. Ellmerer*, B. Balent*, L. Schaupp*, G. J. Krejs* and T. R. Pieber* Abstract Aims In intensi®ed insulin therapy, the recent development of short-acting insulinanalogueswithaveryrapidonsetofactionforcesanewdiscussionin terms of the optimal injection±meal interval. This study evaluated prandial glycaemia in patients with Type 1 diabetes following the subcutaneous injectionofsolublehumaninsulin(HI)andtheinsulinanalogueinsulinaspart (IAsp) at different injection±meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control. Methods In a randomized, double-blind, double-dummy, four-period crossoverstudy,20Type1diabeticpatientswereinvestigated.Prandialinsulin wasadministered15minbeforethestartofthemeal(HI (±15min) ),immediately before the meal (HI (0min) ; IAsp (0min) ) and 15 min after the start of the meal (IAsp (+15min) ). Results Plasma glucose excursions from baseline levels during the 4 h (PG exc ) were highest with HI (0min) (17.9 mmol.l ±1 .h; P < 0.05 vs. other treatments) and were not statistically different for HI (±15min) , IAsp (0min) and IAsp (15min) (13.6, 11.9 and 14.2 mmol.l ±1 .h, respectively). Maximum concentration of plasmaglucose(PG max )waslowestwithIAsp (0min) (11.2 mmol/l; P <0.05vs. other treatments). PG max was comparable with HI (±15min) , HI (0min) and IAsp (+15min) (13.3,14.1and13.2mmol/l,respectively). Conclusions With regard to prandial glycaemia IAsp (+15min) is as effective as HI (± 5min) and superior to HI (0min) . Thus, post-prandial dosing of the insulin analogue IAsp offers an attractive and feasible therapeutic option for well- controlledpatientswithType1diabetesmellitus. Diabet.Med.17,371±375(2000) Keywords injection±meal interval, insulin analogue, insulin aspart, insulin therapy,solublehumaninsulin Abbreviations ANOVA, analysis of variance; AUC, area under the curve; BMI, body mass index; HI, soluble human insulin; IAsp, insulin analogue insulin aspart; PG exc, plasma glucose excursions from baseline values; PG max, maxi- mumconcentrationofplasmaglucose *Department of Internal Medicine, Karl-Franzens University, Graz, Austria ²Novo Nordisk A/S Germany Received 2 September 1999; revised 7 February 2000; accepted 13 March 2000 Correspondence to: Dr Gernot A. Brunner, Department of Internal Medicine, Karl-Franzens University, Auenbruggerplatz 15, A±8036 Graz, Austria. E-mail: gernot.brunner@kfunigraz.ac.at ã 2000 British Diabetic Association. Diabetic Medicine, 17, 371±375 371