Background Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes mellitus (DM). MODY12 is a rare subtype, with few cases reported in China to date.

Objective To explore the clinical characteristics, genetic testing, and clinical management of MODY12, so as to enhance the understanding and management of this condition.

Methods A retrospective analysis was conducted on the clinical data about a patient with MODY12 caused by mutation in the ATP-binding cassette subfamily C member 8 (ABCC8) gene, supplemented by literature review.

Results The patient was a 32-year-old female with BMI of 22.06 kg/m². She was hospitalized due to pancreatitis, during which examinations revealed a fasting blood glucose level of 11.99 mmol/L, a random blood glucose level of 21.07 mmol/L, and a glycated hemoglobin (HbA1c) level of 9.3%. Her fasting insulin was 15.112 μU/mL, with a peak postprandial insulin level of 55.747 μU/mL. The fasting C-peptide was 0.49 ng/mL, and the peak postprandial C-peptide was 3.04 ng/mL. All diabetes-related autoantibodies were negative, leading to a suspicion of a special type of diabetes. Whole-exome sequencing of the patient's familial genomic DNA, verified by Sanger sequencing in relatives, revealed that both the patient and her father carried a heterozygous ABCC8 (NM_000352.6) c.824G > A (p. Arg275Gln) mutation. Multiple bioinformatics tools predicted this variant to be pathogenic. Initially treated with basal insulin combined with miglitol, the patient was switched to low-dose sulfonylurea (glimepiride 1 mg/day) after genetic confirmation, achieving optimal glycemic control during follow-up.

Conclusion For young- or middle-aged-onset diabetes patients with negative autoantibodies, preserved pancreatic function, and no significant insulin resistance, MODY should be considered. For confirmed MODY12 cases with genetic testing, low-dose sulfonylurea therapy can achieve excellent glycemic control while avoiding unnecessary long-term insulin injections.