Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies
Clinical Snapshot
PICO Framework
| P — Population | Human subjects aged ≥50 years with Type 2 Diabetes Mellitus (n=3,522), Parkinson's disease (n=722), and healthy controls (n=3,277) |
| I — Intervention | Measurement of oxidative stress biomarkers F2-isoprostanes and 8-OHdG |
| C — Comparator | Healthy controls and between-disease comparisons |
| O — Outcomes | Serum, plasma, or leukocyte levels of F2-isoprostanes (lipid peroxidation marker) and 8-OHdG (DNA damage marker) |
Bottom Line
This meta-analysis of 54 studies demonstrates distinct oxidative stress profiles between Type 2 diabetes and Parkinson's disease. In T2DM, both F2-isoprostanes and 8-OHdG are markedly elevated with large effect sizes, particularly in patients with complications like nephropathy. In PD, only 8-OHdG shows moderate elevation while F2-isoprostanes remain unchanged. The finding that 8-OHdG is elevated in both conditions suggests potential utility in PD-T2DM comorbidity assessment. However, extremely high heterogeneity (I²>90%) severely limits confidence in pooled estimates, reflecting substantial methodological variability across studies. The lack of standardized assay protocols and unclear study quality assessment further compromise clinical applicability. While these biomarkers show promise for understanding oxidative stress mechanisms in neurometabolic diseases, current evidence is insufficient to support routine clinical use. Future research requiring standardized methodologies and longitudinal designs is essential before these biomarkers can inform clinical practice or therapeutic monitoring.
Key Findings
P Value: T2DM biomarkers: p<0.001; PD 8-OHdG: p=0.011; PD F2-isoprostanes: NS
Effect Size: T2DM: F2-isoprostanes g=1.60, 8-OHdG g=2.64; PD: F2-isoprostanes g=0.47 (NS), 8-OHdG g=0.78
Primary Outcome: Oxidative stress biomarker levels compared between disease groups and controls
Nnt Or Sensitivity: Extreme oxidative stress in diabetic nephropathy (g=5.24); 8-OHdG shows consistent elevation across both conditions
Confidence Interval: T2DM F2-isoprostanes: 0.95-2.25; T2DM 8-OHdG: 2.13-3.14; PD 8-OHdG: 0.18-1.39
Clinical Application
Limited by lack of standardized assays and high methodological variability between laboratories Relevant to Australian diabetes and neurology practice; however, biomarker testing not currently PBS-subsidized for routine oxidative stress assessment. May inform future TGA considerations for diagnostic biomarkers Adults ≥50 years with T2DM or PD, particularly relevant for comorbid presentations
Abstract
BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.
References
- 1.Msigwa, S. S., Mkwambe, M. C., Yu, Q. Y., Zhu, S. G., Zhu, J. H., Zhang, X., & Wang, J. Y. (2026). Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies. Annals of Medicine. https://doi.org/10.1080/07853890.2026.2654251
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