ORF10-05 - Clinical and Genetic Characteristics of Neonatal Diabetes: A Single-Center Study

Objective: To collect and analyze clinical data of infants diagnosed with diabetes before 12 months of age, and summarize the clinical and genetic characteristics of Neonatal Diabetes(NDM).

Methods: This single-center retrospective study enrolled infants aged =12 months diagnosed with diabetes who visited the Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University between April 2011 and December 2025. Clinical data included demographic information (age, weight, sex), family history, and clinical manifestations. Laboratory tests encompassed fasting blood glucose, insulin, C-peptide, glycated hemoglobin (HbA1c), and diabetes-related autoantibodies. Genetic testing was recommended, and retrospective analyses were performed based on integrated clinical and genetic data.

Results: A total of 25 NDM cases were included, 24 diagnosed before 6 months of age and 1 at 7 months. The cohort consisted of 14 males and 11 females, with no specific syndromic features identified. Onset age ranged from birth to 6 months (mean: 1.73±1.55 months), and the mean HbA1c level was 7.48±3.33%. Diabetic ketoacidosis (DKA) was present in 17 (68.0%) patients at diagnosis. Fourteen cases (56.0%) were classified as permanent neonatal diabetes mellitus (PNDM) and 11 (44.0%) as transient neonatal diabetes mellitus (TNDM). Six infants had a birth weight < 2500g, and 1 had a gestational age < 37 weeks. Genetic testing was performed in 20 patients, with pathogenic or likely pathogenic mutations detected in 15 (75.0%): KCNJ11 (8 cases), ABCC8 (3 cases), INS (2 cases), and IRS2 (1 case). Among KCNJ11 mutation carriers, 5 had PNDM and 3 had TNDM; ABCC8 mutations were associated with 2 PNDM and 1 TNDM cases; both INS mutation cases were PNDM, and the IRS2 mutation case was TNDM. Seven PNDM patients received oral sulfonylurea therapy, with 6 achieving adequate glycemic control (4 with KCNJ11 mutations, 1 with ABCC8 mutation, 1 with negative genetic testing). One KCNJ11 mutation carrier switched to insulin therapy due to suboptimal control. Genotypic characteristics distinguishing PNDM and TNDM were summarized through retrospective analysis.

Conclusion: PNDM is associated with more severe clinical manifestations and a higher incidence of DKA. Clinical phenotypes of NDM correlate with specific genotypes, and early genetic testing is of significant clinical value for accurate diagnosis and individualized treatment.