INTRAMUSCULAR VERSUS SUBCUTANEOUS INJECTION OF SOLUBLE AND LISPRO INSULIN - COMPARISON OF METABOLIC EFFECTS IN HEALTHY-SUBJECTS

The aim of this study was to compare the glucodynamic effects of solub le insulin and the rapid acting insulin analogue insulin lispro after subcutaneous (s.c.) and intramuscular (i.m.) injection. Twelve healthy male volunteers (age 26.8 +/- 1.7 years, BMI 23.2 +/- 2.3 kg m(-2); m ean +/- SD) participated in this single-centre, open-labelled, euglyca emic glucose clamp study on four different days. Soluble insulin or in sulin lispro (0.2 U kg(-1)) were injected s.c. or i.m. into the thigh by syringe. The glucodynamic effects were assessed by registering the glucose infusion rates necessary to maintain blood glucose at 5.0 mmol l(-1) for the subsequent 420 min. Intramuscular injection of soluble insulin led to an earlier peak of metabolic action when compared to s. c. administered soluble insulin (t(max) 138 +/- 29 vs 179 +/- 34 min; p < 0.05). The maximal metabolic effect and metabolic activity during the first 2 h after i.m. and s.c. injection of soluble insulin were co mparable (GIR(max) 9.7 +/- 2.3 vs 7.8 +/- 2.3 mg kg(-1) min(-1); n.s., AUC(0-120) min 0.60 +/- 0.18 vs 0.50 +/- 0.15 g kg(-1) 120 min; n.s.) . Subcutaneous administration of insulin lispro led to a metabolic eff ect resembling that induced by i.m. application of soluble insulin (t( max) 116 +/- 26 vs 138 +/- 29 min; n.s., GIR(max) 11.1 +/- 2.3 mg vs 9 .7 +/- mg kg(-1) min(-1); n.s.). However, the overall metabolic respon se during the first 2 h after injection was higher with s.c. insulin l ispro (AUC(0-120) (min) 0.81 +/- 0.26 vs 0.60 +/- 0.18 g kg(-1) 120 mi n; p < 0.05). The glucodynamic activity of i.m. applied insulin lispro was comparable to that of lispro s.c.. Following i.m. injection of so luble insulin, the metabolic activity peaked more rapidly than with s. c. administration. In contrast, the metabolic effect of insulin lispro was similar with either route. The time-action profile of i.m. inject ed soluble insulin lies between that of s.c. applied soluble insulin a nd insulin lispro. (C) 1998 John Wiley & Sons, Ltd.