GCK-MODY With Concurrent Islet Autoimmunity in a Child With Mild Stable Hyperglycemia: A Case Report

Background Diabetes in childhood is increasingly recognized as a heterogeneous condition that includes autoimmune, type 2, and monogenic forms. Glucokinase maturity-onset diabetes of the young (GCK-MODY) typically causes mild stable fasting hyperglycemia and is usually managed without pharmacologic therapy, whereas autoimmune type 1 diabetes is characterized by immune-mediated beta-cell injury that may progress through presymptomatic stages before overt hyperglycemia. When these features coexist, diagnostic classification and longitudinal follow-up become challenging. Case Presentation We report a 7-year-11-month-old boy evaluated for mild persistent hyperglycemia. Fasting plasma glucose ranged from 107–111 mg/dL, HbA1c from 6.01–6.20%, andoral glucose tolerance testing showed fasting plasma glucose of 109 mg/dL and 2-hour plasma glucose of 127 mg/dL. Fasting C-peptide was preserved at 1.63 ng/mL. Islet autoantibody testing demonstrated strongly positive glutamic acid decarboxylase 65 antibody (257.5 IU/mL) and positive zinc transporter 8 antibody (20.61 U/mL), while insulinoma-associated antigen-2 antibody was negative. Genetic testing identified a heterozygous likely pathogenic GCK variant, c.469G>A (p.Glu157Lys), consistent with GCK-MODY. Continuous glucose monitoring showed mean glucose of 120 mg/dL, glucose management indicator of 6.2%, time in range of 98%, and coefficient of variation of 17.7%. Discussion The child's mild stable fasting hyperglycemia, non-diabetic 2-hour oral glucose tolerance test value, preserved C-peptide, and low-variability continuous glucose monitoring profile were compatible with GCK-MODY. However, positive glutamic acid decarboxylase 65 and zinc transporter 8 antibodies indicated concurrent islet autoimmunity with potential future progression toward autoimmune type 1 diabetes. Because GCK-MODY itself can explain mild dysglycemia, the child should not be automatically classified as having stage 2 type 1 diabetes without evidence of progression beyond the expected GCK-MODY phenotype. Conclusion This case illustrates that positive islet autoantibodies do not exclude monogenic diabetes. In children with mild stable fasting hyperglycemia, preserved C-peptide secretion, and non-diabetic oral glucose tolerance test values, genetic testing remains important for accurate phenotypic classification. When GCK-MODY coexists with islet autoimmunity, longitudinal metabolic surveillance is required to detect progression beyond the expected GCK-MODY phenotype.