Modeling the glucose regulatory system in extreme preterm infants

Background: Premature infants represent a significant proportion of the neonatal intensive care population. Blood glucose homeostasis in this group is often disturbed by immaturity of endogenous regulatory systems and the stress of their condition. Hypo- and hyperglycemia are frequently reported in very low birth weight infants, and more mature infants often experience low levels of glycemia. A model capturing the unique fundamental dynamics of the neonatal glucose regulatory system could be used to develop better blood glucose control methods.Methods: A metabolic system model is adapted from adult critical care to the unique physiological case of the neonate. Integral-based fitting methods were used to identify time-varying insulin sensitivity and non-insulin mediated glucose uptake profiles. The clinically important predictive ability of the model was assessed by assuming insulin sensitivity was constant over prediction intervals of 1, 2 and 4h forward and comparing model-simulated versus actual clinical glucose values for all recorded interventions. The clinical data included 1091 glucose measurements over 3567 total patient hours, along with all associated insulin and nutritional infusion data, for N = 25 total cases. Ethics approval was obtained from the Upper South A Regional Ethics Committee for this study. Results: The identified model had a median absolute percentage error of 2.4% [IQR: 0.9-4.8%) between model-fitted and clinical glucose values. Median absolute prediction errors at 1-, 2- and 4-h intervals were 5.2% [IQR: 2.5-10.3%], 9.4% [IQR: 4.5-18.4%] and 13.6% [IQR: 6.3-27.6%] respectively.Conclusions: The model accurately captures and predicts the fundamental dynamic behaviors of the neonatal metabolism well enough for effective clinical decision support in glycemic control. The adaptation from adult to a neonatal case is based on the data from the literature. Low prediction errors and very low fitting errors indicate that the fundamental dynamics of glucose metabolism in both premature neonates and critical care adults can be described by similar mathematical models. (C) 2010 Published by Elsevier Ireland Ltd.

背景：早产儿在新生儿重症监护人群中占相当大的比例。这一群体的血糖内稳态常常因内源性调节系统不成熟以及自身病情的应激而受到干扰。极低出生体重儿经常出现低血糖和高血糖情况，而较成熟的婴儿往往会出现低血糖水平。一个能够捕捉新生儿葡萄糖调节系统独特基本动态的模型可用于开发更好的血糖控制方法。 方法：一个代谢系统模型从成人重症监护调整适用于新生儿的独特生理情况。采用基于积分的拟合方法来确定随时间变化的胰岛素敏感性以及非胰岛素介导的葡萄糖摄取曲线。通过假设胰岛素敏感性在向前1、2和4小时的预测区间内是恒定的，并比较所有记录干预措施的模型模拟血糖值与实际临床血糖值，来评估该模型在临床上重要的预测能力。临床数据包括25例患者总共3567小时内的1091次血糖测量值，以及所有相关的胰岛素和营养输注数据。本研究获得了上南A地区伦理委员会的伦理批准。 结果：所确定的模型在模型拟合血糖值和临床血糖值之间的中位绝对百分比误差为2.4%[四分位距：0.9 - 4.8%]。在1、2和4小时间隔的中位绝对预测误差分别为5.2%[四分位距：2.5 - 10.3%]、9.4%[四分位距：4.5 - 18.4%]和13.6%[四分位距：6.3 - 27.6%]。 结论：该模型能够足够准确地捕捉和预测新生儿代谢的基本动态行为，从而为血糖控制提供有效的临床决策支持。从成人到新生儿情况的调整是基于文献数据。较低的预测误差和极低的拟合误差表明，早产儿和重症监护成人的葡萄糖代谢基本动态可以用类似的数学模型来描述。（C）2010年由爱思唯尔爱尔兰有限公司出版