Data-driven identification of temporal glucose patterns in a large cohort of nondiabetic patients with COVID-19 using time-series clustering

Objective: Hyperglycemia has emerged as an important clinical manifestation of coronavirus disease 2019 (COVID-19) in diabetic and nondiabetic patients. Whether these glycemic changes are specific to a subgroup of patients and persist following COVID-19 resolution remains to be elucidated. This work aimed to characterize longitudinal random blood glucose in a large cohort of nondiabetic patients diagnosed with COVID-19. Materials and Methods: De-identified electronic medical records of 7502 patients diagnosed with COVID-19 without prior diagnosis of diabetes between January 1, 2020, and November 18, 2020, were accessed through the TriNetX Research Network. Glucose measurements, diagnostic codes, medication codes, laboratory values, vital signs, and demographics were extracted before, during, and after COVID-19 diagnosis. Unsupervised time-series clustering algorithms were trained to identify distinct clusters of glucose trajectories. Cluster associations were tested for demographic variables, COVID-19 severity, glucose-altering medications, glucose values, and new-onset diabetes diagnoses. Results: Time-series clustering identified a low-complexity model with 3 clusters and a high-complexity model with 19 clusters as the best-performing models. In both models, cluster membership differed significantly by death status, COVID-19 severity, and glucose levels. Clusters membership in the 19 cluster model also differed significantly by age, sex, and new-onset diabetes mellitus. Discussion and Conclusion: This work identified distinct longitudinal blood glucose changes associated with subclinical glucose dysfunction in the low-complexity model and increased new-onset diabetes incidence in the high-complexity model. Together, these findings highlight the utility of data-driven techniques to elucidate longitudinal glycemic dysfunction in patients with COVID-19 and provide clinical evidence for further evaluation of the role of COVID-19 in diabetes pathogenesis.