Shrestha Rupendra T, Kumar Anjali F, Taddese Abdisa, Khowaja Ameer A, Moheet Amir, Olawsky Evan, Eberly Lynn E, Seaquist Elizabeth R
Department of Medicine Division of Diabetes, Endocrinology and Metabolism University of Minnesota Minneapolis Minnesota.
Division of Biostatistics School of Public Health University of Minnesota Minneapolis Minnesota.
Endocrinol Diabetes Metab. 2018 Sep 10;1(4):e00041. doi: 10.1002/edm2.41. eCollection 2018 Oct.
Although regular human U-500 insulin (U-500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U-500 insulin in obese insulin resistant subjects with type 2 diabetes.
Randomized double-blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U-500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia.
A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200-unit dose of U-500 insulin was significantly greater than the time following a 100-unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study.
The duration of action of U-500 increases when dose is increased from 100 to 200 units. Neither dose of U-500 insulin has an onset of action before 2.5 hours after administration. This suggests that U-500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.
尽管常规人U - 500胰岛素（U - 500）常用于胰岛素抵抗的2型糖尿病患者，但缺乏针对这些个体的药代动力学和药效学研究。我们着手确定两剂U - 500胰岛素在肥胖的2型糖尿病胰岛素抵抗受试者中的起效速率、作用持续时间和总体降糖效果。
设计随机双盲交叉研究，对受试者单次皮下注射100或200单位的U - 500胰岛素，然后根据需要静脉输注葡萄糖以维持血糖正常。
共研究了12名受试者。200单位剂量的U - 500胰岛素后维持血糖正常所需静脉输注葡萄糖的时间显著长于100单位剂量后。在与起效速率相关的指标或研究期间维持血糖正常所需静脉葡萄糖总量方面，各剂量间未发现差异。
当剂量从100单位增加到200单位时，U - 500的作用持续时间增加。两剂U - 500胰岛素在给药后2.5小时内均未起效。这表明U - 500不应作为餐时大剂量胰岛素用于降低餐后两小时血糖，并且随着剂量增加，给药间隔可能需要延长以避免低血糖。
