Clinical and genetic characterization and long-term evaluation of individuals with maturity-onset diabetes of the young (MODY): The journey towards appropriate treatment

To describe the clinical and genetic characteristics and long-term follow-up of a cohort with maturity-onset diabetes of the young (MODY), and to evaluate how molecular diagnosis impacted on treatment.A large observational, retrospective, cohort study included individuals referred to the University of São Paulo's Monogenic Diabetes Unit between 2011 and 2020. Comprehensive clinical and genetic evaluations were performed.Overall, 228 individuals (190 GCK-MODY and 38 HNF1A-MODY) were enrolled. Sixty-two different GCK gene mutations (5 novel) and 17 HNF1A gene mutations (2 novel) were found. Data were available on treatment status for 76 index individuals with GCK-MODY. Before molecular diagnosis, nutritional intervention alone was used in 41 cases (53.9%). After molecular diagnosis, this number increased to 72 (94.8%). Glycated haemoglobin (HbA1c) remained stable over the 6-year follow-up period: 6.5% (47 mmol/mol) at the first and 6.3% (45 mmol/mol) at the final visit (p = 0.056). Prior to molecular diagnosis, 7/21 (33.3%) HNF1A-MODY individuals were using sulfonylurea compared to 17/21 (81%) after testing. After a median of 5 years on sulfonylureas, HbA1c values improved from 7.5% (58 mmol/mol) to 6.5% (48 mmol/mol) (p = 0.006).Molecular diagnosis resulted in appropriate adjustment of treatment in approximately 80% of participants with GCK-MODY or HNF1A-MODY.