A preliminary screening framework to distinguish m.3243A > G-related diabetes from early-onset type 2 diabetes (EOD) in China

This study aimed to develop a preliminary screening framework to identify patients with early-onset type 2 diabetes (EOD) who require genetic testing for m.3243A>G-related diabetes, thereby facilitating precise diagnosis and personalized therapeutic management. A retrospective cross-sectional study was conducted of 118 hospitalized EOD patients (diagnosed ≤45 years). Sanger sequencing detected the mitochondrial DNA m.3243A > G pathogenic variant, categorizing patients into the m.3243A>G-related diabetes group and EOD group. Clinical characteristics and laboratory parameters were compared between the groups, and receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of potential screening indicators. Of all patients, 8 (6.8%) tested positive for the m.3243A > G pathogenic variant. Compared with the EOD group, patients with m.3243A>G-related diabetes exhibited lower BMI, C-peptide levels at measured time points, triglycerides (TG), and serum phosphorus (all P < 0.05). BMI showed the highest diagnostic accuracy (AUC = 0.989, cut-off value = 19.85 kg/m 2 ). The m.3243A>G heteroplasmy level was negatively correlated with patient age at admission and disease duration. A preliminary screening strategy integrating BMI, C-peptide dynamics, TG, and serum phosphorus effectively identifies EOD patients requiring genetic testing for m.3243A>G-related diabetes. This approach supports timely diagnosis, avoids inappropriate treatment, and optimizes outcomes for these patients. • Clinical screening distinguishes two diabetes types in Chinese for precision. • Mitochondrial diabetes: lower body mass, insulin peptide, fat/phosphorus. • Body mass (19.85 kg/m 2 ) is top index with high sensitivity/specificity. • Mitochondrial mutation correlates with age, disease duration and severity. • Propose a preliminary screening framework for m.3243A>G-related diabetes.