THE ACTION PROFILE OF LISPRO IS NOT BLUNTED BY MIXING IN THE SYRINGE WITH NPH INSULIN

OBJECTIVE - To assess the effect of mixing the insulin analog lispro ( Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile.RESEARCH DESIGN AND METHODS - A total of 12 healthy vo lunteers received subcutaneous abdominal injections of 0.1 U/kg regula r insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe u p to 2 min before single injection (treatment group B), and human regu lar insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintai ned for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacod ynamic parameters were compared by analysis of variance for repeated m easures. RESULTS - Peak plasma insulin levels (2.6 +/- 0.8 vs. 2.2 +/- 0.6 vs. 1.9 +/- 0.6 ng/ml, P = 0.075), total glucose infused (121.5 /- 32.8 vs. 135.0 +/- 49.0 vs. 117.3 +/- 39.9 mg . kg(-1) . min(-1), P = 0.53), and maximum glucose infusion rate (GIR(max)) (8.3 +/- 0.9 vs . 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg . kg(-1) . min(-1), P = 0.65) were no t significantly different between treatments. The times until peak ins ulin concentrations were similar in treatment groups A and B, but sign ificantly shorter than in treatment group C (0.9 +/- 0.3 and 1.2 +/- 0 .2 vs. 2.0 +/- 0.4 h, respectively, P = 0.042). The times until GIR(ma x) were also not different (113.9 +/- 41 and 122.0 +/- 45 vs. 209.0 +/ - 51.3 min, , respectively, P = 0.002). The glucose infusion rate (GIR ) then fell to 50% GIR(max) more quickly in treatment groups A and B t han in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005). CONCLUSIONS - The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe i mmediately before injection. The advantages are available to those ind ividuals who need to combine types of insulin before injection to achi eve optimal diabetes control.