Identifying subtypes of type 2 diabetes mellitus with machine learning: development, internal validation, prognostic validation and medication burden in linked electronic health records in 420 448 individuals.

introductionNone of the studies of type 2 diabetes (T2D) subtyping to date have used linked population-level data for incident and prevalent T2D, incorporating a diverse set of variables, explainable methods for cluster characterization, or adhered to an established framework. We aimed to develop and validate machine learning (ML)-informed subtypes for type 2 diabetes mellitus (T2D) using nationally representative data. RESEARCH DESIGN AND

methodsIn population-based electronic health records (2006-2020; Clinical Practice Research Datalink) in individuals ≥18 years with incident T2D (n=420 448), we included factors (n=3787), including demography, history, examination, biomarkers and medications. Using a published framework, we identified subtypes through nine unsupervised ML methods (K-means, K-means++, K-mode, K-prototype, mini-batch, agglomerative hierarchical clustering, Birch, Gaussian mixture models, and consensus clustering). We characterized clusters using intracluster distributions and explainable artificial intelligence (AI) techniques. We evaluated subtypes for (1) internal validity (within dataset; across methods); (2) prognostic validity (prediction for 5-year all-cause mortality, hospitalization and new chronic diseases); and (3) medication burden.

results

conclusionsIn the largest study using ML to date in incident T2D, we identified four distinct subtypes, with potential future implications for etiology, therapeutics, and risk prediction.