Joseph S E, Korzon-Burakowska A, Woodworth J R, Evans M, Hopkins D, Janes J M, Amiel S A
Department of Medicine, King's College School of Medicine and Dentistry, London, England, U.K.
Diabetes Care. 1998 Dec;21(12):2098-102. doi: 10.2337/diacare.21.12.2098.
To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile.
A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular 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 up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures.
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 (GIRmax) (8.3 +/- 0.9 vs. 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg.kg-1.min-1, P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly 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 GIRmax 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% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005).
The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine types of insulin before injection to achieve optimal diabetes control.
评估注射前将胰岛素类似物赖脯胰岛素（优泌乐）与中性鱼精蛋白锌胰岛素（优泌林I）混合对赖脯胰岛素快速、短效作用模式的影响。
12名健康志愿者接受如下皮下腹部注射：0.1U/kg常规胰岛素和0.2U/kg中性鱼精蛋白锌胰岛素，分别为：赖脯胰岛素和中性鱼精蛋白锌胰岛素分开注射（治疗组A），赖脯胰岛素和中性鱼精蛋白锌胰岛素在单次注射前2分钟内在注射器中混合（治疗组B），以及人常规胰岛素和中性鱼精蛋白锌胰岛素按治疗组B的方式混合并注射（治疗组C），在不同时间，随机顺序进行。通过静脉输注20%葡萄糖使血浆葡萄糖维持12小时。通过重复测量方差分析比较药代动力学和药效学参数。
各治疗组间的血浆胰岛素峰值水平（2.6±0.8 vs. 2.2±0.6 vs. 1.9±0.6 ng/ml，P = 0.075）、总葡萄糖输注量（121.5±32.8 vs. 135.0±49.0 vs. 117.3±39.9 mg·kg-1·min-1，P = 0.53）和最大葡萄糖输注率（GIRmax）（8.3±0.9 vs. 8.0±1.7 vs. 7.1±2.4 mg·kg-1·min-1，P = 0.65）无显著差异。治疗组A和B达到胰岛素峰值浓度的时间相似，但显著短于治疗组C（分别为0.9±0.3和1.2±0.2 vs. 2.0±0.4小时，P = 0.042）。达到GIRmax的时间也无差异（分别为113.9±41和122.0±45 vs. 209.0±51.3分钟，P = 0.002）。然后，治疗组A和B的葡萄糖输注率（GIR）降至50%GIRmax的速度比治疗组C更快（分别为239.9±40.5 vs. 292.4±133.3 vs. 399.5±78.3，P = 0.005）。
注射前立即在注射器中将赖脯胰岛素与中性鱼精蛋白锌胰岛素混合不会减弱赖脯胰岛素的作用模式。对于那些需要在注射前混合不同类型胰岛素以实现最佳糖尿病控制的个体而言，这一优势是存在的。
