B-249 Exploring Mitochondrial DNA Variations in Type 2 Diabetes Mellitus and Their Implications for Maternally Inherited Diabetes and Deafness Using MassARRAY Analysis

Background Type 2 Diabetes Mellitus (T2DM) is a multifactorial metabolic disorder influenced by genetic and environmental factors. Emerging evidence suggests that mitochondrial DNA (mtDNA) variations contribute to the pathogenesis of T2DM, particularly in cases of Maternally Inherited Diabetes and Deafness (MIDD). Understanding these mtDNA variations could provide insights into mitochondrial dysfunction, insulin resistance, and ß-cell failure, paving the way for precision medicine approaches. Methods This study employed MassARRAY technology to analyze mtDNA variations in a cohort of 20 participants, including 15 T2DM patients and 5 non-diabetic controls. DNA was extracted from EDTA blood samples, and specific mtDNA loci, including A12026G and C12258A, were targeted for mutation analysis. Genotype frequencies were compared between T2DM and control groups. Statistical analysis was performed using chi-square tests and logistic regression to evaluate the association between mtDNA variations and T2DM risk. Results Most individuals exhibited wild-type (WT) mtDNA genotypes across the analyzed loci. However, two significant mutations were identified in the T2DM group. The A12026G mutation was observed in one patient and was associated with MIDD, suggesting a potential link to mitochondrial dysfunction. Another patient exhibited heteroplasmy at the C12258A locus, indicating mitochondrial instability. No mutations were detected in the control group. Statistical analysis revealed a significant association between the A12026G mutation and increased risk of T2DM (p < 0.05). Conclusion This study suggests that specific mtDNA variations, particularly A12026G and C12258A, may contribute to the pathogenesis of T2DM through mitochondrial dysfunction, leading to insulin resistance and ß-cell failure. The association of A12026G with MIDD reinforces the role of mitochondrial inheritance in diabetes susceptibility. These findings highlight the potential of mtDNA mutations as biomarkers for early detection and risk assessment in T2DM. Future research with larger cohorts is needed to validate these associations and explore mitochondrial-targeted therapies for diabetes management.