Algorithmic identification of atypical diabetes in electronic health record (EHR) systems

Aims Understanding atypical forms of diabetes (AD) may advance precision medicine, but methods to identify such patients are needed. We propose an electronic health record (EHR)-based algorithmic approach to identify patients who may have AD, specifically those with insulin-sufficient, non-metabolic diabetes, in order to improve feasibility of identifying these patients through detailed chart review. Methods Patients with likely T2D were selected using a validated machine-learning (ML) algorithm applied to EHR data. "Typical" T2D cases were removed by excluding individuals with obesity, evidence of dyslipidemia, antibody-positive diabetes, or cystic fibrosis. To filter out likely type 1 diabetes (T1D) cases, we applied six additional "branch algorithms," relying on various clinical characteristics, which resulted in six overlapping cohorts. Diabetes type was classified by manual chart review as atypical, not atypical, or indeterminate due to missing information. Results Of 114,975 biobank participants, the algorithms collectively identified 119 (0.1%) potential AD cases, of which 16 (0.014%) were confirmed after expert review. The branch algorithm that excluded T1D based on outpatient insulin use had the highest percentage yield of AD (13 of 27; 48.2% yield). Together, the 16 AD cases had significantly lower BMI and higher HDL than either unselected T1D or T2D cases identified by ML algorithms (P<0.05). Compared to the ML T1D group, the AD group had a significantly higher T2D polygenic score (P<0.01) and lower hemoglobin A1c (P<0.01). Conclusion Our EHR-based algorithms followed by manual chart review identified collectively 16 individuals with AD, representing 0.22% of biobank enrollees with T2D. With a maximum yield of 48% cases after manual chart review, our algorithms have the potential to drastically improve efficiency of AD identification. Recognizing patients with AD may inform on the heterogeneity of T2D and facilitate enrollment in studies like the Rare and Atypical Diabetes Network (RADIANT).