Kildegaard Jonas, Christensen Toke Folke, Johansen Mette Dencker, Randløv Jette, Hejlesen Ole K
Department of Health Science and Technology, University of Aalborg, Aalborg, Denmark.
Diabetes Technol Ther. 2007 Dec;9(6):501-7. doi: 10.1089/dia.2007.0242.
Adrenaline is often studied in people with type 1 diabetes during hypoglycemic episodes. Adrenaline is difficult and costly to measure, and therefore a pharmacokinetic model of adrenaline can be a supportive tool that adds information and saves measurements resources.
We have developed a compartment model of adrenaline secretion and elimination. It is based on input on physical exercise, blood glucose level, and optional infused adrenaline. The model parameters are identified using least square regression on published data of adrenaline kinetics measured in a number of different clinical studies.
Simulation of published adrenaline measurements shows agreement with data of adrenaline infusion (R(2) = 0.9), exercise (R(2) = 0.97), and hypoglycemic episodes (R(2) = 0.93-0.97). The identified function describing adrenaline secretion during hypoglycemia shows an exponential increase for a blood glucose decreasing below 3.5 mmol/L and an approaching maximum around 1 mmol/L. Exercise intensity increasing above 50% of maximal oxygen uptake maximum causes approximately exponential increase in adrenaline secretion.
The model is a simple tool that can be used to simulate and predict adrenaline concentrations in situations of hypoglycemia, physical exercise, and adrenaline infusion. In conclusion, the developed model, although simple, seems to be useful for simulating adrenaline dynamics in situations with hypoglycemic episodes, physical exercise, or infusion.
肾上腺素常被用于研究1型糖尿病患者的低血糖发作情况。肾上腺素的测量难度大且成本高,因此肾上腺素的药代动力学模型可作为一种辅助工具,提供更多信息并节省测量资源。
我们建立了一个肾上腺素分泌与消除的房室模型。该模型基于体育锻炼、血糖水平以及选择性注入肾上腺素等输入信息。模型参数通过对多项不同临床研究中测得的肾上腺素动力学已发表数据进行最小二乘回归来确定。
对已发表的肾上腺素测量数据进行模拟,结果显示与肾上腺素输注(R² = 0.9)、运动(R² = 0.97)以及低血糖发作(R² = 0.93 - 0.97)的数据相符。所确定的描述低血糖期间肾上腺素分泌的函数表明,当血糖降至3.5 mmol/L以下时呈指数增加,在血糖约为1 mmol/L时接近最大值。运动强度超过最大摄氧量最大值的50%时,肾上腺素分泌会大致呈指数增加。
该模型是一个简单工具,可用于模拟和预测低血糖、体育锻炼及肾上腺素输注情况下的肾上腺素浓度。总之,所开发的模型虽简单,但似乎对模拟低血糖发作、体育锻炼或输注情况下的肾上腺素动态变化很有用。