Endocrine Abstracts

JOINT2869

Background: Maturity-Onset Diabetes of the Young (MODY) due to GCK mutations is a form of monogenic diabetes characterized by mild fasting hyperglycemia. Here, we present a pediatric case of GCK-MODY diagnosed after Multisystem Inflammatory Syndrome in Children (MIS-C).

Case: A 4-year-old girl, born at term with a birth weight of 3,200 g, was referred for persistent hyperglycemia. She had been hospitalized for three weeks due to MIS-C, before her visit. Family history revealed diabetes in her maternal grandfather, aunt and mother necessitating the use of antidiabetic medications, which raised concerns for MODY. Initial labs showed fasting glucose of 120 mg/dL and HbA1c of 5.4%. An OGTT revealed 0-minute glucose of 136 mg/dL and 120-minute glucose of 151 mg/dL, with an insulin response suggesting preserved beta-cell function. Genetic testing identified a heterozygous pathogenic variant in GCK (c.214G>A, p.Gly72Arg, rs193922289), confirming GCK-MODY. However during follow-up after MIS-C, postprandial hyperglycemia and an HbA1c of 8% raised concerns for insulinopenic diabetes. Further rise of blood glucose levels necessitated use of insulin. Autoimmune diabetes markers (IAA, ICA, GADA) were negative. The patient was also screened for other antibodies related to autoimmune thyroiditis and celiac disease, which were negative. After 6 months of treatment, insulin was discontinued.Duringthelast 2.5 years of follow-up,the patient remained stable, with anHbA1c of 5.9%at her last visit.

Discussion: Recent studies suggest COVID-19 may increase diabetes risk, but its exact role is unclear. The mechanisms likely involve systemic inflammation, glucocorticoid use, endothelial dysfunction, and persistent viral presence affecting pancreatic β-cell function and insulin sensitivity. Some propose classifying post-COVID diabetes as a distinct syndrome. In this case, initial postprandial hyperglycemia and an HbA1c of 8% raised concerns for insulinopenic diabetes, leading to autoantibody testing. However, negative autoantibodies, stable glucose after insulin withdrawal, and the presence of a GCK variant suggest transient hyperglycemia was MIS-C-induced. The exact mechanism remains unknown, highlighting the need for long-term follow-up. This case also underscores the importance of considering MODY in pediatric patients with persistent hyperglycemia with strong family history. Dynamic follow-up and a tailored approach are crucial to avoiding unnecessary treatments.