Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes
Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes
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DOI：
10.2337/diabetes.53.6.1614
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发表时间：
2004-06-01
期刊：
影响因子：
7.7
通讯作者：
Draeger, E
中科院分区：
文献类型：
--
作者：
Heise, T;Nosek, L;Draeger, E
这项随机双盲研究的目的是比较新型胰岛素类似物地特胰岛素与甘精胰岛素和NPH胰岛素在1型糖尿病患者中降糖作用的受试者内变异性。54名受试者（32名男性和22名女性，年龄38 ± 10岁[平均值+/- SD]，BMI 24 ± 2 kg/m2，HbA（1c）7.5 ± 1.2%，糖尿病病程18 ± 9年）参与了该平行组比较。在4个相同的研究日，每例受试者在正葡萄糖钳夹条件下（目标血糖浓度5.5 mmol/l）接受4次单次皮下注射0.4单位/kg地特胰岛素（n = 18）、甘精胰岛素（n = 16）或人NPH胰岛素（n = 17）。记录给药后24小时基础胰岛素制剂的药效学（葡萄糖输注速率[GIR]）和药代动力学（地特胰岛素、人胰岛素和甘精胰岛素的血清浓度）特性。根据研究的药效学终点的变异系数（CV）评估，地特胰岛素的受试者内变异性显著低于NPH胰岛素和甘精胰岛素[GIR-AUC（（o-12 h））27%（地特胰岛素）vs. 59%（NPH）vs. 46%（甘精胰岛素）; GIR-AUC（（0-24 h））27 vs. 68 vs. 48%; GIR（max）23 vs. 46 vs. 36%;所有比较P < 0.001]。地特胰岛素的药代动力学终点的受试者内变异性也较小：最大浓度（C-max）18 vs. 24 vs. 34%; INS-AUC（o-无穷大）14 vs. 28 vs. 33%。结果表明，地特胰岛素的降糖作用显著优于NPH胰岛素和甘精胰岛素。
The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 10 years [mean +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18), insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC((o-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h)) 27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration (C-max) 18 vs. 24 vs. 34%; INS-AUC(o-infinity) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine.