ESPE Abstracts

Background: Maturity-onset diabetes of the young (MODY) represents 1-5% of all patients with diabetes mellitus (DM) and numerous genes have been found to be associated with it. While mutations of the insulin gene (INS) are better known to cause permanent neonatal diabetes mellitus, several rare disease-causing variants have also been identified in patients with MODY. Patients with INS-MODY demonstrate variable clinical phenotypes – ranging from milder forms that require only lifestyle or oral agent, to more severe forms requiring lifelong insulin.

Main findings: We present a case of MODY arising from a novel disease-causing INS variant, in an adolescent patient who presents with atypical clinical features. Our patient was obese with clinical evidence of insulin resistance and was diagnosed with DM through opportunistic oral glucose tolerance test (OGTT) screen. He subsequently developed symptomatic hyperglycemia with worsening glycemic trend, requiring treatment with high dose insulin and metformin. After 2.5 years, his glycemic profile normalized following significant weight loss, and pharmacotherapy was discontinued entirely. Targeted gene panel testing in patient and his parents revealed a de novo novel missense variant in exon 2 of the INS gene (p.His29Tyr), confirmed using bidirectional Sanger sequencing.

Conclusion: In patients with MODY, insulin resistance as a comorbidity can worsen the clinical course, affect treatment and risks of long-term complications. Management of DM patients as such will need to be individualized. This case highlights the utility of genetic testing in diagnosing the rarer and more variable forms of MODY, particularly in cases with atypical features.