Insulin glulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese non-diabetic subjects
Insulin glulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese non-diabetic subjects
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DOI：
10.1055/s-2005-865806
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发表时间：
2005-09-01
影响因子：
1.8
通讯作者：
Scholtz, H
中科院分区：
文献类型：
--
作者：
Becker, RHA;Frick, AD;Scholtz, H
目的/假设：本研究在肥胖受试者中比较了赖谷胰岛素、赖脯胰岛素和常规人胰岛素的药代动力学和药效学。研究方法：在这项单次给药、随机、双盲、交叉的神经钳夹试验中，18名非糖尿病受试者（平均体重指数[BMI] 34.7kg（.）m（-2））随机接受皮下注射每种胰岛素（0.3 U（.）kg（-1））。结果：赖谷胰岛素和赖脯胰岛素比常规人胰岛素具有更快的起效曲线。谷赖胰岛素和赖脯胰岛素的葡萄糖输注率分数（GIR）-GIR曲线的曲线下面积（AUC）和最大GIR均大于常规人胰岛素。赖谷胰岛素的总葡萄糖处置略高于常规人胰岛素，与赖脯胰岛素相当，尽管所有胰岛素的总葡萄糖处置均随胰岛素抵抗（HOMA指数）增加而降低。与常规人胰岛素相比，谷赖胰岛素和赖脯胰岛素达到20%（早期葡萄糖处置）和80%（大部分活性）总GIR-AUC的时间更短。谷赖胰岛素和赖脯胰岛素相对于常规人胰岛素的滞留药代动力学特征更快、更短，证明了这一点，达到20%总INS-AUC、INS-C-max（INS-t（max））和平均滞留时间更短。此外，至总GIR-AUC 20%的时间显示赖脯胰岛素的速效性低于赖谷胰岛素，这与赖脯胰岛素的药代动力学特征略慢一致。与赖脯胰岛素和常规人胰岛素不同，BMI或皮下脂肪厚度与赖谷胰岛素的药代动力学或药效学特征之间无显著相关性。结论/解释：在肥胖非糖尿病受试者中，谷赖胰岛素和赖脯胰岛素的时间-作用曲线显著快于常规人胰岛素，无论BMI和皮下脂肪厚度如何，谷赖胰岛素均占优势。
Aims/hypothesis: This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine, insulin lispro, and regular human insulin in obese subjects. Methods: In this single-dose, randomized, double-blind, crossover euglycaernic clamp study, 18 non-diabetic subjects (mean body mass index [BMI] 34.7kg(.)m(-2)) were randomized to receive subcutaneous injections of each insulin (0.3 U(.)kg(-1)) in pre-determined sequences. Results: Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin. Fractional glucose infusion rate (GIR)-area under curves (AUC) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin. Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin, and was comparable to insulin lispro, although it decreased with increasing insulin resistance (HOMA index) with all insulins. Time to 20% (early glucose disposal) and 80% (bulk of activity) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin. This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin, evidenced by shorter times to 20% of total INS-AUC, INS-C-max (INS-t(max)), and mean residence time. Moreover, time to 20% of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine, which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro. There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine, unlike insulin lispro and regular human insulin. Conclusions/interpretation: Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects, which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness.