Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Diabetes Obes Metab. 2013 Mar;15(3):241-5. doi: 10.1111/dom.12016. Epub 2012 Oct 22.
To compare the pharmacodynamic properties of insulin detemir (detemir) and neutral protamine lispro (NPL) insulin using a euglycaemic glucose clamp.
In a double-blind, crossover study, 30 patients with C-peptide negative type 1 diabetes were randomly assigned to a single dose (0.4 U/kg) of detemir and NPL. Plasma glucose (PG) was normalized with a variable insulin infusion and then decreased stepwise, followed by a euglycaemic clamp at 5.5 mmol/l over 32 h. Duration of action was defined as time from dosing until PG exceeded 8.3 mmol/l for at least 30 min.
Duration of action was similar for detemir [23.0 (range 2.25-32) h] and NPL [22.0 (9.5-32) h], p = 0.55. Using glucose infusion rate (GIR) parameters, detemir showed a flatter pharmacodynamic profile versus NPL: area under the curve, AUC(GIR) ((0-32)) = 1326 vs. 1841 mg/kg, p < 0.01 (detemir vs. NPL, respectively); AUC(GIR) ((0-12)) = 784 vs. 1392 mg/kg, p < 0.05; AUC(GIR) ((12-32)) = 455 vs. 274 mg/kg, p = 0.051; GIR(late) (12-32)/GIR(early) (0-12) ratio = 0.33 vs. 0.04, p < 0.001. Detemir also showed a lower and later peak of action than NPL [GIR(max) 2.0 vs. 3.2 mg/kg/min, p < 0.01; T(max) 9.1 (95% confidence interval: 3.0-14.7) vs. 7.0 h (1.8-15.2)].
Detemir and NPL had similar duration of action of approximately 24 h in patients with type 1 diabetes. Compared with NPL, detemir had a flatter profile with a more even distribution of metabolic effect over 24 h.
通过正葡萄糖钳夹比较胰岛素地特胰岛素（detemir）和中性鱼精蛋白锌胰岛素（NPL）的药效学特性。
在一项双盲、交叉研究中，将 30 例 C-肽阴性 1 型糖尿病患者随机分为单次剂量（0.4 U/kg）的 detemir 和 NPL 组。通过可变胰岛素输注使血糖（PG）正常化，然后逐步降低，接着在 32 小时内将 PG 钳夹在 5.5 mmol/l 进行 32 小时。作用持续时间定义为 PG 超过 8.3 mmol/l 至少 30 分钟的时间。
detemir [23.0（范围 2.25-32）h]和 NPL [22.0（9.5-32）h]的作用持续时间相似，p=0.55。使用葡萄糖输注率（GIR）参数，detemir 与 NPL 相比表现出更平坦的药效学特征：AUC(GIR)（0-32）分别为 1326 和 1841 mg/kg，p<0.01（detemir 与 NPL 相比）；AUC(GIR)（0-12）分别为 784 和 1392 mg/kg，p<0.05；AUC(GIR)（12-32）分别为 455 和 274 mg/kg，p=0.051；GIR(late)（12-32）/GIR(early)（0-12）比值分别为 0.33 和 0.04，p<0.001。detemir 的作用峰值也低于 NPL，且出现时间更晚[GIR(max)分别为 2.0 和 3.2 mg/kg/min，p<0.01；T(max)分别为 9.1（95%置信区间：3.0-14.7）和 7.0 h（1.8-15.2）]。
在 1 型糖尿病患者中，detemir 和 NPL 的作用持续时间相似，约为 24 小时。与 NPL 相比，detemir 具有更平坦的特征，24 小时内代谢效应分布更均匀。
