MITOCHONDRIAL DNA MUTATIONS AND THEIR ROLE IN EARLY-ONSET TYPE 2 DIABETES

Abstract

Background: Early-onset type 2 diabetes mellitus (T2DM) is becoming an increasing health concern, particularly among younger populations. Although lifestyle and environmental factors contribute to disease development, genetic abnormalities involved in cellular energy metabolism may also influence diabetes progression. Mitochondrial DNA (mtDNA) mutations can affect oxidative phosphorylation, increase oxidative stress, and disturb insulin secretion pathways.

Objective: This research investigates mitochondrial DNA mutations in patients with early-onset type 2 diabetes. It will analyze energy metabolism-related gene defects. The study aims to explore metabolic-genetic linkage in diabetes progression. It may open pathways for mitochondrial-based therapies

Study Type: Molecular genetic study

Methods: A molecular genetic study was conducted among 120 patients diagnosed with early-onset T2DM and 60 healthy controls. Clinical and biochemical parameters, including fasting blood glucose, glycated hemoglobin (HbA1c), fasting insulin, and insulin resistance index (HOMA-IR), were evaluated. Peripheral blood samples were collected, and mitochondrial DNA was extracted for targeted genetic analysis. Selected mitochondrial regions associated with energy metabolism, including MT-TL1, MT-ND1, MT-ND4, and MT-CYB, were analyzed using molecular sequencing approaches. Identified variants were evaluated through bioinformatics analysis and correlated with clinical characteristics.

Results: Mitochondrial DNA alterations were detected more frequently among diabetic participants compared with controls. Approximately 41.7% of early-onset T2DM patients carried significant mtDNA variants, with the highest frequency observed in regions involved in mitochondrial protein synthesis and respiratory chain activity. Mutation-positive patients showed higher HbA1c levels, increased HOMA-IR values, and greater metabolic disturbance compared with mutation-negative individuals. The MT-TL1 A3243G variant and other respiratory chain-related alterations were associated with impaired glucose regulation and mitochondrial dysfunction.

Conclusion: The findings indicate that mitochondrial DNA mutations may contribute to early-onset T2DM by affecting mitochondrial energy production, oxidative balance, and insulin regulation. Mitochondrial genetic analysis may provide valuable information for understanding disease mechanisms and developing personalized strategies for early diagnosis and future mitochondrial-targeted therapies.