Kang S, Creagh F M, Peters J R, Brange J, Vølund A, Owens D R
Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
Diabetes Care. 1991 Jul;14(7):571-7. doi: 10.2337/diacare.14.7.571.
To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100).
Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal.
Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case).
Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.
比较皮下注射三种新型人胰岛素类似物（天冬酰胺B10；天冬酰胺B9、谷氨酸B27；以及天冬酰胺B28）与注射可溶性人胰岛素（中性胰岛素HM U-100）后的餐后血糖波动及血浆游离胰岛素类似物水平。
6名胰岛素依赖型糖尿病男性受试者，间隔至少1周，在过夜禁食及基础胰岛素输注后，于标准500千卡餐食前30分钟皮下注射72纳摩尔（约12单位）可溶性人胰岛素，或在餐食前即刻皮下注射72纳摩尔的三种类似物中的每一种。
4个研究日的平均基础血糖相似。与人类胰岛素（6.3±0.8毫摩尔）相比，天冬酰胺B10（5.4±0.8毫摩尔）和天冬酰胺B9、谷氨酸B27（5.4±0.7毫摩尔）类似物注射后的平均±标准误峰值血糖增量相似，而天冬酰胺B28类似物注射后的峰值血糖增量显著更低（3.6±1.2毫摩尔，P<0.02）。相对于可溶性人胰岛素（100%±标准误21），0至240分钟期间葡萄糖曲线下的增量面积分别为79%±34（天冬酰胺B10，无显著差异）、70%±29（天冬酰胺B9、谷氨酸B27，无显著差异）和43%±23（天冬酰胺B28，P<0.02）。4个研究日的基础血浆游离胰岛素水平相似。血浆游离胰岛素类似物水平在注射后30分钟迅速升至峰值，分别为308±44皮摩尔（天冬酰胺B10）；1231±190皮摩尔（天冬酰胺B9、谷氨酸B27）和414±42皮摩尔（天冬酰胺B28），且显著高于相应的（即餐后30分钟）血浆游离胰岛素水平157±15皮摩尔（每种情况P<0.02）。
皮下注射后，胰岛素类似物的血浆曲线比人胰岛素更符合生理情况。餐食前即刻注射的所有三种类似物至少与提前30分钟注射的可溶性人胰岛素一样有效。这些类似物有望成为未来短效胰岛素的潜在候选药物。
