AUTHOR=Zhang Xin , Xie Jiajia , You Xiong , Gong Houwu 

TITLE=Risk factors and drug discovery for cognitive impairment in type 2 diabetes mellitus using artificial intelligence interpretation and graph neural networks

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1213711

DOI=10.3389/fendo.2023.1213711

ISSN=1664-2392

ABSTRACT=Background: Among the 382 million diabetic patients worldwide, around 30% experience neuropathy, and 1/5 of these patients eventually develop diabetes cognitive impairment (CI). However, the mechanism underlying diabetes CI remains unknown, and early diagnostic methods or effective treatments are currently not available.
Objective: This study aimed to explore the risk factors for CI in patients with type 2 diabetes mellitus (T2DM), screen potential therapeutic drugs for T2DM-CI, and provide evidence for preventing and treating T2DM-CI. 
Methods: This study focused on the T2DM population admitted to the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine and the First Affiliated Hospital of Hunan University of Chinese Medicine. Sociodemographic data and clinical objective indicators of T2DM patients admitted from January 2018 to December 2022 were collected. Based on the Montreal Cognitive Assessment (MoCA) Scale scores, 719 patients were categorized into two groups, the T2DM-CI group with CI and the T2DM-N group with normal cognition. The survey content included demographic characteristics, laboratory serological indicators, complications, and medication information. Six machine learning algorithms were used to analyze the risk factors of T2DM-CI, and the Shapley method was used to enhance model interpretability. Furthermore, we developed a graph neural network (GNN) model to identify potential drugs associated with T2DM-CI.
Results: Our results showed that the T2DM-CI risk prediction model based on Catboost exhibited superior performance with an AUC of 0.95 (specificity 93.17%, and sensitivity 78.58%). Diabetes duration, age, education level, AST, drinking, and intestinal flora were identified as risk factors for T2DM-CI. The top 10 potential drugs related to T2DM-CI, including Metformin, Liraglutide, and Lixisenatide, were selected by the GNN model. Some herbs, such as licorice and cuscutae semen, were also included. Finally, we discovered the mechanism of herbal medicine interventions in gut microbiota.
Conclusions: The method based on Interpreting AI and GNN can identify the risk factors and potential drugs associated with T2DM-CI.