Development of a Calculator for HNF1A- and HNF4A-MODY in Asian Indians

We aimed to develop a calculator to determine the probability of having HNF1A-MODY (hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young) or HNF4A (hepatocyte nuclear factor 4 alpha)-MODY (the commonest forms of MODY) in Asian Indians using clinical and biochemical criteria.

We extracted data on individuals with young-onset diabetes aged <30 years (n = 29 191) from electronic records. Genetically confirmed HNF1A- and HNF4A-MODY (n = 55) were selected along with 1000 individuals each of type 1 diabetes (T1D) and type 2 diabetes (T2D). These data sets were used to develop a classification model using logistic regression. The model's performance was evaluated using receiver operating characteristic (ROC) curves in an internal data set and validated in an external data set.

Eight predictive models were constructed, beginning with a basic model that included variables, such as age at diagnosis, body mass index (BMI), parental history, and glycated hemoglobin (HbA1c) (models 1 and 5). High-density lipoprotein (HDL) cholesterol was added in models 2 and 6, stimulated C-peptide in models 3 and 7, and all predictors were combined in models 4 and 8. Models 1 to 4, designed to distinguish MODY from T1D, achieved an ROC-area under the curve (AUC) value ranging from 0.884 to 0.957, while models 5 to 8, aimed at differentiating MODY from T2D, achieved an ROC-AUC value ranging from 0.914 to 0.936. All models demonstrated excellent performance in internal validation, with high five-fold cross-validation c-statistics. An online calculator using these models estimates MODY probability that is accessible at https://mdrf-t1d-calculator.shinyapps.io/MODY/.

We developed an ethnicity-specific calculator to help identify individuals with possible HNF1A-MODY or HNF4A-MODY in Asian Indians. This user-friendly, web-based tool would be helpful to select candidates for genetic testing in this population.