1147-P: Monogenic Obesity and Type 2 Diabetes Linked to Pathogenic DYRK1B Variants-A Comprehensive Study

Introduction: Dual-specificity tyrosine phosphorylation-regulated kinase 1B is implicated in metabolic processes, and its variants have been hypothesized to contribute significantly to obesity and T2D development. This study focuses on understanding the role of pathogenic, total loss-of-function variants in the DYRK1B gene in monogenic obesity and its association with Type 2 Diabetes (T2D). Methods: A cohort of 240 individuals diagnosed with monogenic obesity and T2D was examined. Genetic sequencing was used to identify loss-of-function variants in the DYRK1B gene. Participants' metabolic profiles, including glucose and insulin levels, were monitored. Statistical analysis included logistic regression to determine the association between DYRK1B variants and disease phenotypes, and Kaplan-Meier curves were used to assess the onset of T2D in relation to obesity. Results: Pathogenic DYRK1B variants were identified in 60% of the participants. Those with these variants presented earlier onset and higher severity of obesity and T2D compared to those without. The statistical analysis showed a significant correlation (p < 0.05) between the presence of these variants and early-onset obesity and T2D. Conclusion: The study establishes a strong link between pathogenic, total loss-of-function variants in the DYRK1B gene and the development of monogenic obesity associated with T2D. These findings highlight the importance of genetic screening in individuals with early-onset obesity and T2D for targeted interventions. This research opens avenues for personalized treatment strategies and better management of these conditions based on genetic profiling.