Genetic Variants and Therapeutic Approaches in Maturity-Onset Diabetes of the Young: A Retrospective Analysis

ContextIdentifying Maturity-Onset Diabetes of the Young (MODY) in patients with diabetes is essential because treatment differs significantly from other forms of diabetes. We identified patients with MODY gene variants and evaluated their clinical characteristics and responses to treatment. Evidence AcquisitionWe identified 106 patients with genetic MODY variants. Demographics, islet autoantibodies at diabetes diagnosis, co-morbidities, and response to treatment by genetic variant were evaluated. Evidence SynthesisPatients diagnosed with MODY variants comprised 4% of the total population with diabetes. Mean age and HbA1c of patients with MODY at diagnosis were 10.5 years and 8.2%, respectively. Surprisingly, diabetic ketoacidosis was a presenting feature for some (n=7, 6.8%), and others with MODY had positive islet cell autoantibodies (n= 7, 6.6%). Variants in HNF1A, GCK, and HNF1B were frequently observed (20%, 22%, and 17% respectively), while rare variants in PDX1, RFX6, BLK, and CNOT1 were uncovered. Initial and follow up treatment of patients with MODY were compared. For each medication (Insulin, Metformin, Sulfonylureas, and GLP-1 receptor agonists), a reduction in HbA1c was observed at follow-up (0.3-21%). Insulin and sulfonylureas were associated with an increase in average BMI (insulin: +8.23%, n=21, sulfonylurea: +0.63%, n=12) at follow-up, metformin was intermediate (-2.46%, n=4), and GLP-1 receptor agonists demonstrated the greatest decrease in BMI (-4.79%, n=4). ConclusionsThe presence of islet autoantibodies or diabetic ketoacidosis does not preclude the diagnosis of MODY. Given the observed improvements in BMI and HbA1c, further investigation into the use of GLP-1 receptor agonists as treatment for MODY should be considered.