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正常人体内胰岛素全身给药速率的计算。

Calculation of the systemic delivery rate of insulin in normal man.

作者信息

Polonsky K S, Given B D, Pugh W, Licinio-Paixao J, Thompson J E, Karrison T, Rubenstein A H

出版信息

J Clin Endocrinol Metab. 1986 Jul;63(1):113-8. doi: 10.1210/jcem-63-1-113.

DOI:10.1210/jcem-63-1-113
PMID:3519643
Abstract

The accuracy with which the systemic delivery rate of insulin can be estimated from peripheral insulin concentrations was investigated in eight normal men. Endogenous insulin secretion was suppressed by somatostatin, and insulin was infused exogenously via a peripheral vein. The infusion rate was progressively increased and then decreased to stimulate the changes in insulin secretion that occur after a secretory stimulus. The infusion rate of insulin was then estimated by analyzing peripheral insulin concentrations using both single and two-compartment mathematical models and was compared with the actual infusion rates. Model parameters were measured in each subject by analysis of the insulin decay curve after a bolus injection. Estimated infusion rates based on the single compartment model were 84.3 +/- 3.0% (mean +/- SE) of the actual infusion rate as it was increasing and 110.3 +/- 3.7% of the infusion rate as it was decreasing. The mean overall absolute percent error associated with this approach was 14.1 +/- 1.0% (range, 10.2-18.8%), and model estimates of the total amount of insulin infused over the duration of the experiment were 97.1 +/- 3.2% of the quantity actually infused (range, 85.4-110.7%). Estimates of the infusion rate based on a two-compartment model represented 90.3 +/- 3.1% of the actual infusion rate as it was increasing and 98.2 +/- 3.2% of the actual rate as it was falling. The area under the derived infusion rate curve was 94.8 +/- 2.8% of the area under the actual curve. The overall error associated with the use of the two-compartment model was 12.9 +/- 1.1% (range, 8.8-18.6%). Differences between the single and two-compartment models were minor and not statistically significant. These data demonstrate that under euglycemic conditions, changes in the plasma insulin concentration within the physiological range are not associated with changes in the clearance kinetic rate constants of the hormone. Furthermore, the systemic delivery rate of insulin can be accurately derived from peripheral insulin concentrations using either a single or two-compartmental model if model parameters are accurately measured in individual subjects by analysis of insulin decay curves.

摘要

在8名正常男性中研究了根据外周胰岛素浓度估算胰岛素全身输送率的准确性。通过生长抑素抑制内源性胰岛素分泌,并通过外周静脉外源性输注胰岛素。输注速率逐渐增加然后降低,以刺激分泌刺激后发生的胰岛素分泌变化。然后使用单室和双室数学模型通过分析外周胰岛素浓度来估算胰岛素的输注速率,并与实际输注速率进行比较。通过分析推注注射后的胰岛素衰减曲线来测量每个受试者的模型参数。基于单室模型的估计输注速率在增加时为实际输注速率的84.3±3.0%(平均值±标准误),在降低时为输注速率的110.3±3.7%。与该方法相关的平均总体绝对百分比误差为14.1±1.0%(范围为10.2 - 18.8%),并且在实验持续时间内输注的胰岛素总量的模型估计值为实际输注量的97.1±3.2%(范围为85.4 - 110.7%)。基于双室模型的输注速率估计值在增加时占实际输注速率的90.3±3.1%,在下降时占实际速率的98.2±3.2%。推导的输注速率曲线下的面积为实际曲线下面积的94.8±2.8%。与使用双室模型相关的总体误差为12.9±1.1%(范围为8.8 - 18.6%)。单室和双室模型之间的差异很小且无统计学意义。这些数据表明,在血糖正常的条件下,生理范围内血浆胰岛素浓度的变化与激素清除动力学速率常数的变化无关。此外,如果通过分析胰岛素衰减曲线在个体受试者中准确测量模型参数,则可以使用单室或双室模型从外周胰岛素浓度准确推导胰岛素的全身输送率。

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Diabetes: Models, Signals, and Control.
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