融合生理模型与序列预测,提升1型糖尿病患者长时程血糖预测精度。
PhysioSeq2Seq: A Hybrid Physiological Digital Twin and Sequence-to-Sequence LSTM for Long-Horizon Glucose Forecasting in Type 1 Diabetes
- 用数字孪生匹配个体生理状态,注入序列模型作为外部变量。
- 240分钟预测误差仅39.28毫克/分升,偏差降低13.89毫克/分升。
- 适合临床闭环胰岛素系统开发,对个体化医疗有重要意义。
精准的长时程血糖预测对自动化胰岛素输注系统至关重要,可帮助1型糖尿病(T1D)患者管理血糖并避免严重低血糖。然而,标准递归长短期记忆(LSTM)网络在长时程预测中因误差累积产生系统性负偏差,而纯机制性常微分方程(ODE)模型在群体参数化下缺乏个体泛化能力。本文提出PhysioSeq2Seq,一种结合患者特异性生理建模与序列到序列(Seq2Seq)LSTM的混合架构。对于每个血糖片段,孪生匹配在300个参数化数字孪生体中搜索,基于3小时连续葡萄糖监测(CGM)历史找到最佳生理匹配。匹配孪生体的10个内部状态变量作为外生协变量注入到Seq2Seq LSTM的编码器和解码器中。该同步48步预测策略消除了递归误差累积,而ODE特征提供物理约束,将长时程漂移限制在生理合理范围内。PhysioSeq2Seq在348名参与者来自T1DEXI数据集的CGM和胰岛素数据上训练,并在74名预留参与者上评估。在240分钟预测时,平均绝对误差为39.28毫克/分升,均值误差为-10.62毫克/分升,相比递归LSTM偏差降低13.89毫克/分升,相比基于ODE的数字孪生平均绝对误差减少28.62毫克/分升。结果表明,消除架构反馈并注入个体匹配的生理状态,是提升T1D长时程血糖预测的有效且临床有意义的策略。
原文摘要 · Abstract (English)
Accurate long-horizon glucose forecasting is critical for automated insulin delivery systems, which help people with type 1 diabetes (T1D) manage their glucose and avoid dangerous hypoglycemia. However, standard recursive long short-term memory (LSTM) networks suffer from systematic negative bias at longer horizons due to error compounding, while purely mechanistic ordinary differential equation (ODE) models fail to generalize across individuals when parameterized at the population level. We propose PhysioSeq2Seq, a hybrid architecture that combines patient-specific physiological modeling with a sequence-to-sequence (Seq2Seq) LSTM. For each glucose segment, twin matching searches a population of 300 parameterized digital twins to identify the best-fitting physiological match from a 3-hour continuous glucose monitoring (CGM) history. The 10 internal ODE state variables of the matched twin are injected as exogenous covariates into both the encoder and decoder of the Seq2Seq LSTM. This simultaneous 48-step prediction strategy eliminates recursive error compounding, while the ODE features provide a physics-grounded constraint that bounds long-horizon drift within physiologically plausible ranges. PhysioSeq2Seq was trained on CGM and insulin data from 348 participants in the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset and evaluated on 74 held-out participants. At the 240-minute horizon, PhysioSeq2Seq achieves a mean absolute error of 39.28 mg/dL and a mean error of -10.62 mg/dL, reducing bias by 13.89 mg/dL over the recursive LSTM and reducing mean absolute error by 28.62 mg/dL over the ODE-based digital twin. These results show that eliminating architectural feedback and injecting patient-matched physiological states is an effective and clinically meaningful strategy for long-horizon glucose forecasting in T1D.
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