Holcombe John H, Zalani Sunita, Arora Vipin K, Mast Casey J
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Clin Ther. 2002 Apr;24(4):629-38. doi: 10.1016/s0149-2918(02)85138-4.
Although insulin lispro (insulin LP) has been shown to improve postprandial blood glucose (BG) control and reduce hypoglycemic episodes in adult patients with type I diabetes, there appear to have been few clinical studies focusing on its use in adolescents.
This study compared the effects of insulin LP with those of regular human insulin (insulin R) on postprandial BG control and hypoglycemia in adolescents with type diabetes.
In this crossover, open-label study, adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were randomized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals, in addition to daily intermediate-acting insulin. After 4 months, patients were switched to the alternate treatment sequence. Eight-point BG profiles, hypoglycemia rate, and glycosylated hemoglobin (HbA1c) were measured at baseline and end point.
Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries; 463 were randomized to treatment (228 insulin LP, 235 insulin R), and 457 completed the study. Insulin LP given before breakfast resulted in significantly lower mean (+/-SD) 2-hour postprandial BG levels compared with insulin R (9.7 +/- 4.0 mmol/L vs 10.6 +/- 4.3 mmol/L, respectively; P < 0.001). Insulin LP given before dinner resulted in significantly lower 2-hour postprandial BG levels compared with insulin R (8.6 +/- 3.5 mmol/L vs 9.3 +/- 3.7 mmol/L; P = 0.003). No differences were seen between treatments in 2-hour postprandial BG levels after the midday meal. Mean baseline HbA1c values were similar between sequence groups, and no between-group difference in HbA1c was observed at end point (insulin LP, 8.69% +/- 1.52%; insulin R, 8.70% +/- 1.65%). Treatment with insulin LP resulted in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R (4.02 +/- 4.5 vs 4.37 +/- 4.5, respectively; P = 0.023) and significantly fewer hypoglycemic episodes between midnight and 6 AM (1.0 +/- 1.9 vs 1.7 +/- 2.6; P < 0.001).
In adolescents with type 1 diabetes, insulin LP significantly improved postprandial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population.
尽管赖脯胰岛素已被证明可改善1型糖尿病成年患者的餐后血糖控制并减少低血糖发作，但针对青少年使用该药物的临床研究似乎较少。
本研究比较了赖脯胰岛素与常规人胰岛素对青少年1型糖尿病患者餐后血糖控制及低血糖的影响。
在这项交叉、开放标签研究中，9至18岁处于坦纳II期青春期的青少年被随机分组，除每日中效胰岛素外，一组在饭前立即接受赖脯胰岛素治疗，另一组在饭前30至45分钟接受常规人胰岛素治疗。4个月后，患者转换为交替治疗方案。在基线和终点时测量八点血糖谱、低血糖发生率和糖化血红蛋白（HbA1c）。
来自15个国家53个研究点的481名青少年参与了该研究；463名被随机分组接受治疗（228名接受赖脯胰岛素，235名接受常规人胰岛素），457名完成了研究。早餐前注射赖脯胰岛素导致餐后2小时平均血糖水平显著低于常规人胰岛素（分别为9.7±4.0 mmol/L和10.6±4.3 mmol/L；P<0.001）。晚餐前注射赖脯胰岛素导致餐后2小时血糖水平显著低于常规人胰岛素（8.6±3.5 mmol/L对9.3±3.7 mmol/L；P = 0.003）。午餐后2小时血糖水平在两种治疗之间无差异。各序列组的基线HbA1c平均水平相似，终点时HbA1c在组间无差异（赖脯胰岛素组为8.69%±1.52%；常规人胰岛素组为8.70%±1.65%）。与常规人胰岛素相比，赖脯胰岛素治疗导致每位患者每30天低血糖发作的发生率显著降低（分别为4.02±4.5和4.37±4.5；P = 0.023），且午夜至凌晨6点之间的低血糖发作显著减少（1.0±1.9对1.7±2.6；P<0.001）。
在青少年1型糖尿病患者中，与常规人胰岛素相比，赖脯胰岛素显著改善了餐后血糖控制并减少了夜间低血糖发作。在本研究人群中，赖脯胰岛素作为强化胰岛素治疗方案的一部分耐受性良好且有效。
