McSorley Paul T, Bell Patrick M, Jacobsen Lisbeth Vestergård, Kristensen Allan, Lindholm Anders
Department of Anaesthesia, Altnagelvin Area Hospital, Londonderry, Northern Ireland.
Clin Ther. 2002 Apr;24(4):530-9. doi: 10.1016/s0149-2918(02)85129-3.
The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus.
In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance.
Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with < or = 7 minor and no major hypoglycemic events.
Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.
本研究旨在比较预混胰岛素类似物门冬双相胰岛素（BIAsp 30）与等效预混人双相胰岛素（BHI 30）在2型糖尿病患者中每日两次给药时的药代动力学和药效学。
在这项随机、双盲、交叉试验中，13名患者（平均年龄64岁；基线糖化血红蛋白平均值7.7%；平均体重指数28.1kg/m²）接受了2周的BIAsp 30治疗和2周的BHI 30治疗，分别在晚餐和早餐前立即给药。在每个2周治疗期结束时，使用特定的双侧酶联免疫吸附测定法测定24小时血清胰岛素和葡萄糖曲线。所有药效学和药代动力学终点均采用方差分析进行分析。
治疗期间每日胰岛素总暴露量相似。门冬双相胰岛素30给药后2小时内总胰岛素浓度-时间曲线下的平均面积，晚餐后比人双相胰岛素30大17%，早餐后大44%；两者差异均有统计学意义。门冬双相胰岛素30给药后血清门冬胰岛素的最大浓度在晚餐后（18%）和早餐后（35%）显著更高。门冬双相胰岛素30组早餐后血清胰岛素峰值浓度提前1小时达到，晚餐后提前45分钟达到；差异仅早餐后有统计学意义。门冬双相胰岛素30的平均每日餐时血糖波动（16.2 mmol·h·L⁻¹）显著低于人双相胰岛素30（17.9 mmol·h·L⁻¹）。晚餐和早餐后，门冬双相胰岛素30餐后4小时血糖波动显著低于人双相胰岛素30，但午餐后显著更高。平均24小时和夜间血清葡萄糖浓度相似，两种胰岛素均与≤7次轻度低血糖事件相关，无严重低血糖事件。
在每日两次的治疗方案中，餐前注射门冬双相胰岛素30可显著降低总体餐后血糖波动。当需要改善餐后血糖控制时，这种作用可能很重要。
