2255-P: The Great Mimicker: HNF1A-MODY Misdiagnosed as Type 1 Diabetes in a 16-Year-Old

Introduction and Objective: HNF1A-MODY (MODY 3) is a monogenic disorder characterized by impaired beta-cell function and high sensitivity to sulfonylureas. Due to its presentation in non-obese youth, it is frequently misdiagnosed as Type 1 Diabetes (T1D). Early differentiation is critical to avoid unnecessary lifelong insulin therapy. Methods: A 16-year-old male with a BMI of 25 presented with incidental hyperglycemia (202 mg/dL) and significant glucosuria (>1000 mg/dL). With an A1c of 8.1% and recent weight loss, he was started on a basal-bolus insulin regimen for presumed T1D. However, initial workup revealed negative islet autoantibodies (GAD65, IA-2, ZnT8) and a preserved C-peptide (1.27 ng/mL). Results: Over two years, his insulin requirements remained minimal while his C-peptide increased to 3.24 ng/mL which is unusual for T1DM. Genetic testing confirmed a heterozygous pathogenic variant in HNF1A. He was successfully transitioned from insulin to glipizide CR 5 mg daily. He then maintained excellent glycemic control (A1c 6.3%) on oral therapy alone. Conclusion: Preserved beta-cell function, negative autoimmunity, and a low renal glucose threshold are hallmarks of HNF1A-MODY. HNF1A mutations impair the transcriptional regulation of insulin and glucose transporters. However, the secretagogue pathway remains sensitive to sulfonylureas. Early genetic confirmation is vital to avoid the burden of unnecessary insulin, ensure appropriate family screening, and monitor for long-term complications. In non-obese adolescents with hyperglycemia and negative autoantibodies, clinicians must consider MODY. This case underscores the diagnostic value of longitudinal monitoring of C-peptide and insulin requirements in deciding when to pursue genetic testing for accurate diagnosis and treatment. Disclosure R.E. Arnolda: None. R. Sharma: None.