门冬胰岛素联合中性鱼精蛋白胰岛素在控制餐后血糖中的作用

Postprandial glycemic control using insulin aspart with NPH in inadequately controlled diabetics

目的比较门冬胰岛素（IAsp）和可溶性人胰岛素（HI）分别联合中性鱼精蛋白胰岛素（NPH）在糖尿病治疗中的有效性和安全性。方法220例来自全国5家医院的1型（T1DM）或2型糖尿病（T2DM）患者按1：1的比例随机分为两组，分别接受IAsp或HI联合NPH治疗。以空腹血糖（FPG）、餐后2h血糖（2hPPG）、糖化血红蛋白（HbA1c）及低血糖事件作为评价指标。结果IAsp／NPH组[（14．6±5．3）mmol／L比（8．4±4．I）mmol／L]较HI／NPH组治疗后2hPPG改善更为显著[（14．9±3．9）mmol／L比（10．6±3．5）mmol／L，P〈0．05]，且达标率分别为50．0％、25．5％（P〈0.01）。治疗后IAsp／NPH组[（9．3±1．4）％比（7．7±1．3）％]和HI／NPH组[（9．2±1．2）％比（7．7±1．2）％]HbAlc明显下降，但两组比较差异无统计学意义（P=0．437）。达标率分别为24．5％和14．5％（P〈0．05）。在IAsp／NPH组未见严重低血糖事件和其他不良事件，且夜间低血糖发生率更低（IAsp／NPH：3％，HI／NPH：4％）。IAsp／NPH组与HI／NPH组患者胰岛素日均剂量分别是0．60／0．23IU／kg和0．65／0．24IU／kg。结论IAsp联合NPH能更好地控制餐后血糖，提高患者血糖达标率且不增加夜间低血糖和不良事件的风险。

Objective To compare the efficacy and safety of insulin aspart （IAsp） and human insulin （HI） when applied as meal-time insulin with neutral protamine Hagedorn insulin （NPH） at bedtime in diabetics. Methods A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of I ： 1 into hvo groups accepting IAsp or H/ combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose （FPG）, 2 hour postprandial plasma glucose （2 h PPG）, HbAlc and hypoglycemia. Results A greater reduction in mean 2 h PPG was achieved in the IAsp group [ （ 14. 6 ± 5.3） mmol/L ] as compared with the HI group [ （ 8.4 ± 4. 1 ） mmol/L ] （ P 〈 0. 01, adjusted for baseline value, center effect and diabetes type）. Significantly more IAsp-treated subjects reached the 2 h PPG target （50. 0% vs 25. 5%, P 〈0. 01 ）. HbAlc was reduced more in IAsp/NPH group [（9.3±1.4）% vs （7.7±1.3）%] than in Hi/NPH group [（9.2±1.2）% vs （7.7±1.2）%] . HbAlc target was reached by 24. 5% （IAsp） vs 14. 5% （HI） of subjects （P 〈0.05）. No major hypoglycemia or serious adverse events were observed for the TAsp group. Lower incidence of nocturnal hypoglycemia （IAsp/ NPH： 3% vs HI/NPH： 4% ） was reported in the IAsp group. Average daily insulin doses were 0. 60/0. 23 （IAsp/NPH） and 0. 65/0. 24 （HI/NPH） IU/kg respectively. Conclusion Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.