AccScience Publishing / AIH / Online First / DOI: 10.36922/AIH026130031
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