AccScience Publishing / AIH / Online First / DOI: 10.36922/AIH026130031
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ORIGINAL RESEARCH ARTICLE

Knowledge-constrained neural additive modeling for hypoglycemia risk stratification in older adults with type 2 diabetes

Zheng Rong1† Hui Si2† Wei Bai3† Difei Wang4 Longfeng Sun2 Hui Tian5 Shuangtong Yan5 Xinyu Miao5 Xin Kang1* Xin Hou2*
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1 Department of Computer Science, Tokushima University, Tokushima, Tokushima , Japan
2 Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning , China
3 Department of Aircraft Design, College of Aerospace Engineering, Shenyang Aerospace University, Shenyang, Liaoning , China
4 Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning , China
5 Department of Endocrinology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army General Hospital, Beijing , China
†These authors contributed equally to this work.
Received: 28 March 2026 | Revised: 9 May 2026 | Accepted: 13 May 2026 | Published online: 5 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Hypoglycemia remains a major barrier to safe glucose-lowering treatment in older adults with type 2 diabetes, yet clinically relevant models should combine nonlinear expressiveness, transparent feature attribution, and well-calibrated probability estimates. We developed a knowledge-constrained neural additive model (CNAM) for clinically interpretable stratification of recorded hypoglycemia history in older adults with type 2 diabetes within a multicenter cross-sectional outpatient cohort. The model was evaluated with a locked 10% test split, nested cross-validation, probability calibration, threshold-based decision analysis, decision-curve analysis, and explanation-stability assessment. It achieved competitive locked-test discrimination (receiver operating characteristic [ROC]–area under the curve [AUC] = 0.7350; precision–recall [PR]-AUC = 0.4127) and, after sigmoid calibration fitted on pooled development out-of-fold predictions, showed a calibrated Brier score of 0.1136 and an expected calibration error of 0.0189. Additional operating-point analyses showed trade-offs between sensitivity and specificity, and decision-curve analysis indicated broadly similar net-benefit profiles for CNAM and logistic regression across the evaluated threshold range. The monotonicity-constrained parameterization structurally enforces directionally plausible feature effects on selected predictors, with ablation results providing context against unconstrained variants that exhibit nonzero violations. These findings support CNAM as a complementary, interpretable stratification framework for recorded hypoglycemia history rather than as a replacement for established clinical risk scores. External validation, severity-specific outcome capture, and local recalibration remain necessary before broader clinical use.

Graphical abstract
Keywords
Hypoglycemia
Type 2 diabetes
Older adults
Neural additive models
Calibration
Interpretability
Funding
This study was funded by the Science and Technology Project for the High-Quality Development of China Medical University, with support from the Department of Biotechnology Development and Industrialization (grant 2023JH2/20200110).
Conflict of interest
The authors declare no competing interests.
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Artificial Intelligence in Health, Electronic ISSN: 3029-2387 Print ISSN: 3041-0894, Published by AccScience Publishing