Variability of insulin absorption and insulin action.
Variability of insulin absorption and insulin action.
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DOI：
10.1089/152091502320798312
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Heinemann, Lutz
中科院分区：
文献类型：
--
作者：
Heinemann, Lutz
皮下注射相同剂量的胰岛素可能导致糖尿病患者当前代谢控制的相当大的个体内和个体间差异。这种众所周知的胰岛素代谢作用的可变性极大地阻碍了实际的胰岛素治疗。这篇综述的目的是总结关于这一主题的知识，特别关注肺部注射胰岛素后胰岛素作用的变异性。许多研究已经发表，描述了s.c.库中胰岛素吸收的可变性。只有少数已发表的研究量化了s.c.给药后胰岛素作用的变异性。在受控的实验条件下，s.c.注射常规胰岛素导致某些药效学综合测量的个体内变异系数（CV）为15-25%，这些测量表征了应用胰岛素的代谢作用。个体间变异性比个体内变异性约高10%。据描述，皮下注射的中效和长效胰岛素制剂比皮下注射的常规胰岛素具有更大的变异性（bbb50 %）。然而，在一项葡萄糖钳夹研究中，在健康受试者中，应用NPH胰岛素导致个体内CV在12-45%范围内。这种差异的原因可能是NPH胰岛素悬浮液在制定剂量之前被充分摇晃。与传统胰岛素制剂相比，快速和长效胰岛素类似物似乎具有相似的可变性，这意味着，不幸的是，这些新型胰岛素制剂的发明在可变性方面没有取得相当大的优势。目前还没有合适的研究来调查糖尿病患者服用s.c.胰岛素后代谢效果的可变性。胰岛素吸入是一种新的胰岛素给药方式，目前正处于临床开发阶段。吸入胰岛素引起的代谢效应的可变性目前只在少数（已发表的）研究中进行了研究。在一项健康受试者的葡萄糖钳夹研究中，在三个研究天内吸入相同剂量的胰岛素导致个体内变异性，与s.c.注射常规胰岛素后的可比性相当。在一项针对1型糖尿病患者的剂量反应研究中，0-10小时葡萄糖输注速率曲线下区域的个体内CV为34%。针对2型糖尿病患者的研究表明，个体内CV在s.c.胰岛素给药后的范围内，甚至更低。总之，无论是皮下注射还是吸入，在胰岛素应用后观察到的代谢效应的个体内变异性是相当大的，因此阻碍了实际的糖尿病治疗。到目前为止，还没有发现任何方法可以导致临床相关的可变代谢效应的减少。
Subcutaneous (s.c.) injections of identical insulin doses may lead to considerable intra- and inter-individual differences in the current metabolic control of patients with diabetes mellitus. This well-known variability of the metabolic effect of insulin hampers practical insulin therapy considerably. The aim of this review is to summarize the knowledge about this topic, with a special focus on the variability of insulin action after pulmonary administration of insulin. A number of studies have been published describing the variability of insulin absorption from the s.c. depot. Only in a few published studies has the variability of insulin action after s.c. administration been quantified. Under controlled experimental conditions s.c. injections of regular insulins result in an intra-individual coefficient of variation (CV) of 15-25% of certain pharmacodynamic summary measures--which characterize the metabolic effect of the applied insulin--in healthy subjects. The inter-individual variability was approximately 10% higher than the intra-individual variability. Subcutaneously injected intermediate- and long-acting insulin preparations were described to have an even greater variability (> 50%) than subcutaneously injected regular insulin. However, in a glucose clamp study s.c. application of NPH insulin led to an intra-individual CV in the range of 12-45% in healthy subjects. The reason for this discrepancy might be that the NPH insulin suspension was sufficiently shaken prior to drawing up the dose. Compared with conventional insulin formulations, rapid- and long-acting insulin analogues appear to have a similar variability, which means that, unfortunately, no considerable advantages in terms of variability were achieved by the invention of these novel insulin preparations. There are no appropriate studies available investigating the variability of the metabolic effect after s.c. insulin administration in patients with diabetes. The inhalation of insulin is a novel form of insulin administration that is currently under clinical development. The variability of the metabolic effect induced by the inhalation of insulin has up to now only been investigated in a small number of (published) studies. In a glucose-clamp study with healthy subjects the inhalation of an identical insulin dose on three study days led to an intra-individual variability that was comparable to that after s.c. injection of regular insulin. In a dose-response study with patients with type 1 diabetes the intra-individual CV was 34% for the area under the curve of the glucose infusion rate for 0-10 h. Studies with patients with type 2 diabetes have shown that the intra-individual CVs were within the range seen after s.c. insulin administration or even lower. In summary, the intra-individual variability of the metabolic effect observed after insulin application, be it subcutaneously injected or be it inhaled, is considerable and, therefore, hampers practical diabetes therapy. To date no means have been found that could lead to a clinically relevant reduction in the variable metabolic effect.