Heinemann L, Klappoth W, Rave K, Hompesch B, Linkeschowa R, Heise T
Department of Metabolic Diseases and Nutrition, World Health Organization Collaborating Centre for Diabetes, Heinrich-Heine-University Düsseldorf, Germany.
Diabetes Care. 2000 Sep;23(9):1343-7. doi: 10.2337/diacare.23.9.1343.
To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously
In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration.
After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+/-47 vs. 182+/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+/-2.6 vs. 8.8+/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+/-0.25 vs. 0.59+/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+/-0.76 vs. 2.56+/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+/-3.5% (absolute bioefficacy 10.1+/-3.1%) but was highest in the first 2 h after application (18.5+/-3.7%; absolute bioefficacy 8.2+/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+/-9% for the maximal glucose infusion rate, 15+/-10% for the time-to-maximal effect, and 16+/-12% for the total amount of glucose infused.
This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.
研究吸入87.2单位胰岛素粉末联合吸收增强剂的代谢效应及其效应变异性。将该代谢效应与皮下注射10.2单位常规胰岛素及静脉注射5.5单位常规胰岛素的效应进行比较。
在这项单中心开放性正常血糖葡萄糖钳夹研究中，13名健康男性志愿者在不同的研究日接受5次胰岛素给药：一次静脉给药、一次皮下注射、3次吸入给药，给药顺序随机。给药后8小时内测定将血糖浓度维持在5.0 mmol/l所需的葡萄糖输注率（GIR）。
吸入胰岛素粉末气雾剂后，起效时间明显快于皮下注射胰岛素，且最大作用出现得更早（86±47分钟对182±53分钟，P<0.0001）。吸入胰岛素后的最大葡萄糖输注率与皮下注射胰岛素后的相当（9.2±2.6对8.8±2.8 mg·kg⁻¹·min⁻¹，无显著差异）。吸入后前2小时的代谢效应显著大于皮下注射胰岛素后（输注葡萄糖量：0.88±0.25对0.59±0.20 g·kg⁻¹·120 min⁻¹，P<0.0001）。然而，吸入和皮下注射后的总代谢效应相当（2.50±0.76对2.56±0.69 g·kg⁻¹·480 min⁻¹，无显著差异）。相对于皮下应用胰岛素的数据计算得出的吸入胰岛素相对生物效能为12.0±3.5%（绝对生物效能为10.1±3.1%），但在应用后前2小时最高（18.5±3.7%；绝对生物效能为8.2±4.1%）。胰岛素吸入诱导的代谢反应的个体内变异性，最大葡萄糖输注率为14±9%，达到最大效应时间为15±10%，输注葡萄糖总量为16±12%。
这项可行性研究表明，与之前一项关于无吸收增强剂的吸入胰岛素的研究结果相比，含吸收增强剂的吸入胰岛素具有显著的代谢效应。代谢效应的个体内变异性与吸入及皮下注射胰岛素的相当。
