Biomedical and Biotechnology Research Journal (Jan 2025)

Distinct Roles of Mitochondrial DNA Copy Number, Fibroblast Growth Factor 21, and Growth Differentiation Factor 15 in Glycemic Control, Obesity, and Muscle Health in Type 2 Diabetes Mellitus

  • Abhishek Satheesan,
  • Janardanan Kumar,
  • Leela Kakithakara Vajravelu,
  • Ria Murugesan

DOI
https://doi.org/10.4103/bbrj.bbrj_47_25
Journal volume & issue
Vol. 9, no. 1
pp. 30 – 40

Abstract

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Background: Mitochondrial dysfunction and metabolic stress play critical roles in type 2 diabetes mellitus (T2DM). This cross-sectional study examines the associations of mitochondrial DNA copy number (mtDNA-CN), fibroblast growth factor 21 (FGF21), and growth differentiation factor 15 (GDF15) with metabolic parameters, body composition, and physical performance in T2DM patients. Methods: A total of 181 T2DM patients (mean age: 53.0 years; 98 males, 82 females) were included in the study. Metabolic markers (HbA1c, lipid profile), body composition indices (skeletal muscle index [SMI], body fat percentage [PBF], and physical performance measures (handgrip strength, gait speed) were assessed. Serum mtDNA-CN, FGF21, and GDF15 levels were quantified, and their associations with clinical parameters were analyzed using correlation, regression, and receiver operating characteristic analyses. Results: Higher mtDNA-CN was associated with better glycemic control, lower triglycerides (TAG), and higher SMI (P < 0.001). Serum FGF21 correlated positively with PBF (P < 0.001) and TAG (P < 0.001), showing moderate predictive value for obesity. GDF15 was positively associated with BMI and PBF but had limited discriminatory power for glycemic control (area under the curve = 0.614). Both mtDNA-CN and GDF15 correlated with SMI, suggesting potential roles in muscle health. Conclusion: mtDNA-CN, FGF21, and GDF15 are linked to distinct aspects of metabolic and physical health in T2DM. mtDNA-CN reflects glycemic control and muscle health, FGF21 indicates metabolic disturbances in obesity, and GDF15 is associated with aging-related metabolic dysfunction. These biomarkers provide valuable insights into the interplay between mitochondrial function, metabolic health, and physical performance in T2DM.

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