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基于数据驱动的血糖动力学建模与预测:机器学习在 1 型糖尿病中的应用。

Data-driven modeling and prediction of blood glucose dynamics: Machine learning applications in type 1 diabetes.

机构信息

Department of Computer Science, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.

Norwegian Centre for E-health Research, University Hospital of North Norway, Tromsø, Norway.

出版信息

Artif Intell Med. 2019 Jul;98:109-134. doi: 10.1016/j.artmed.2019.07.007. Epub 2019 Jul 26.

Abstract

BACKGROUND

Diabetes mellitus (DM) is a metabolic disorder that causes abnormal blood glucose (BG) regulation that might result in short and long-term health complications and even death if not properly managed. Currently, there is no cure for diabetes. However, self-management of the disease, especially keeping BG in the recommended range, is central to the treatment. This includes actively tracking BG levels and managing physical activity, diet, and insulin intake. The recent advancements in diabetes technologies and self-management applications have made it easier for patients to have more access to relevant data. In this regard, the development of an artificial pancreas (a closed-loop system), personalized decision systems, and BG event alarms are becoming more apparent than ever. Techniques such as predicting BG (modeling of a personalized profile), and modeling BG dynamics are central to the development of these diabetes management technologies. The increased availability of sufficient patient historical data has paved the way for the introduction of machine learning and its application for intelligent and improved systems for diabetes management. The capability of machine learning to solve complex tasks with dynamic environment and knowledge has contributed to its success in diabetes research.

MOTIVATION

Recently, machine learning and data mining have become popular, with their expanding application in diabetes research and within BG prediction services in particular. Despite the increasing and expanding popularity of machine learning applications in BG prediction services, updated reviews that map and materialize the current trends in modeling options and strategies are lacking within the context of BG prediction (modeling of personalized profile) in type 1 diabetes.

OBJECTIVE

The objective of this review is to develop a compact guide regarding modeling options and strategies of machine learning and a hybrid system focusing on the prediction of BG dynamics in type 1 diabetes. The review covers machine learning approaches pertinent to the controller of an artificial pancreas (closed-loop systems), modeling of personalized profiles, personalized decision support systems, and BG alarm event applications. Generally, the review will identify, assess, analyze, and discuss the current trends of machine learning applications within these contexts.

METHOD

A rigorous literature review was conducted between August 2017 and February 2018 through various online databases, including Google Scholar, PubMed, ScienceDirect, and others. Additionally, peer-reviewed journals and articles were considered. Relevant studies were first identified by reviewing the title, keywords, and abstracts as preliminary filters with our selection criteria, and then we reviewed the full texts of the articles that were found relevant. Information from the selected literature was extracted based on predefined categories, which were based on previous research and further elaborated through brainstorming among the authors.

RESULTS

The initial search was done by analyzing the title, abstract, and keywords. A total of 624 papers were retrieved from DBLP Computer Science (25), Diabetes Technology and Therapeutics (31), Google Scholar (193), IEEE (267), Journal of Diabetes Science and Technology (31), PubMed/Medline (27), and ScienceDirect (50). After removing duplicates from the list, 417 records remained. Then, we independently assessed and screened the articles based on the inclusion and exclusion criteria, which eliminated another 204 papers, leaving 213 relevant papers. After a full-text assessment, 55 articles were left, which were critically analyzed. The inter-rater agreement was measured using a Cohen Kappa test, and disagreements were resolved through discussion.

CONCLUSION

Due to the complexity of BG dynamics, it remains difficult to achieve a universal model that produces an accurate prediction in every circumstance (i.e., hypo/eu/hyperglycemia events). Recently, machine learning techniques have received wider attention and increased popularity in diabetes research in general and BG prediction in particular, coupled with the ever-growing availability of a self-collected health data. The state-of-the-art demonstrates that various machine learning techniques have been tested to predict BG, such as recurrent neural networks, feed-forward neural networks, support vector machines, self-organizing maps, the Gaussian process, genetic algorithm and programs, deep neural networks, and others, using various group of input parameters and training algorithms. The main limitation of the current approaches is the lack of a well-defined approach to estimate carbohydrate intake, which is mainly done manually by individual users and is prone to an error that can severely affect the predictive performance. Moreover, a universal approach has not been established to estimate and quantify the approximate effect of physical activities, stress, and infections on the BG level. No researchers have assessed model predictive performance during stress and infection incidences in a free-living condition, which should be considered in future studies. Furthermore, a little has been done regarding model portability that can capture inter- and intra-variability among patients. It seems that the effect of time lags between the CGM readings and the actual BG levels is not well covered. However, in general, we foresee that these developments might foster the advancement of next-generation BG prediction algorithms, which will make a great contribution in the effort to develop the long-awaited, so-called artificial pancreas (a closed-loop system).

摘要

背景

糖尿病(DM)是一种代谢紊乱,会导致血糖(BG)调节异常,如果得不到适当的治疗,可能会导致短期和长期的健康并发症,甚至死亡。目前,糖尿病尚无根治方法。然而,疾病的自我管理,尤其是将血糖控制在推荐范围内,是治疗的核心。这包括积极跟踪血糖水平以及管理体育活动、饮食和胰岛素摄入量。糖尿病技术和自我管理应用的最新进展使得患者更容易获得相关数据。在这方面,人工胰腺(闭环系统)、个性化决策系统和 BG 事件警报的发展比以往任何时候都更加明显。预测血糖(个性化档案建模)和建模血糖动态等技术是开发这些糖尿病管理技术的核心。患者历史数据的可用性增加为引入机器学习及其在糖尿病管理的智能和改进系统中的应用铺平了道路。机器学习解决具有动态环境和知识的复杂任务的能力为其在糖尿病研究中的成功做出了贡献。

动机

最近,机器学习和数据挖掘变得流行起来,尤其是在糖尿病研究和 BG 预测服务中。尽管机器学习在 BG 预测服务中的应用越来越广泛,但是在 1 型糖尿病的个性化档案建模(预测模型)中,缺乏对建模选项和策略的最新综述,以映射和体现当前趋势。

目的

本综述的目的是开发一个关于机器学习建模选项和策略的简明指南,以及一个专注于 1 型糖尿病 BG 动态预测的混合系统。该综述涵盖了与人工胰腺(闭环系统)控制器、个性化档案建模、个性化决策支持系统和 BG 报警事件应用相关的机器学习方法。总的来说,该综述将确定、评估、分析和讨论这些背景下机器学习应用的当前趋势。

方法

我们在 2017 年 8 月至 2018 年 2 月期间通过各种在线数据库(包括 Google Scholar、PubMed、ScienceDirect 等)进行了严格的文献综述,此外还考虑了同行评审的期刊和文章。首先通过审查标题、关键字和摘要作为初步筛选标准来初步筛选文献,然后我们对发现相关的文章进行全文审查。从选定的文献中提取信息,这些信息基于先前的研究,并通过作者之间的头脑风暴进一步阐述。

结果

最初的搜索是通过分析标题、摘要和关键字进行的。从 DBLP 计算机科学(25)、糖尿病技术与治疗学(31)、Google Scholar(193)、IEEE(267)、糖尿病科学与技术杂志(31)、PubMed/Medline(27)和 ScienceDirect(50)中检索到 624 篇论文。在列表中删除重复项后,剩下 417 条记录。然后,我们根据纳入和排除标准独立评估和筛选文章,这又排除了 204 篇文章,剩下 213 篇相关文章。经过全文评估,剩下 55 篇文章,这些文章进行了批判性分析。使用 Cohen Kappa 检验测量了观察者间的一致性,并且通过讨论解决了分歧。

结论

由于 BG 动态的复杂性,很难实现一种在每种情况下都能产生准确预测的通用模型(即低血糖/高血糖事件)。最近,机器学习技术在糖尿病研究中,特别是在 BG 预测中,受到了更广泛的关注和普及,同时也伴随着自我收集的健康数据的可用性不断增加。最新研究表明,已经测试了各种机器学习技术来预测 BG,例如递归神经网络、前馈神经网络、支持向量机、自组织映射、高斯过程、遗传算法和程序、深度神经网络等,使用各种输入参数组和训练算法。目前方法的主要局限性是缺乏一种明确定义的方法来估计碳水化合物的摄入量,这主要是由个体用户手动完成的,容易出现错误,这可能会严重影响预测性能。此外,还没有建立一种通用的方法来估计和量化体育活动、压力和感染对 BG 水平的近似影响。没有研究人员在自由生活条件下评估应激和感染事件期间的模型预测性能,这应该在未来的研究中考虑。此外,关于模型可移植性的研究很少,模型可移植性可以捕捉患者之间和患者内部的变异性。似乎血糖监测仪读数与实际 BG 水平之间的时间滞后的影响没有得到很好的覆盖。然而,总的来说,我们预计这些发展可能会促进下一代 BG 预测算法的发展,这将为开发期待已久的所谓人工胰腺(闭环系统)做出巨大贡献。

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