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Diabetic microvascular complications frequently coexist and contribute to disease progression. In a meta-analysis published in the Journal of Diabetes & Metabolic Disorders, peripheral blood inflammatory markers and microRNAs were compared across patients with DR, DN, or concurrent DR and DN.

Systematic searches of PubMed, Web of Science, Embase, and the Cochrane Library identified 26 eligible studies. Study quality was assessed using the Newcastle–Ottawa Scale. Meta-analyses evaluated standardized mean differences (SMD), heterogeneity, publication bias using Egger’s test, and sensitivity. Subgroup analyses examined complication subtype and control group characteristics.

Inflammatory markers were significantly elevated across all groups. TNF-α was increased in DR (SMD 1.04, 95% CI 0.56-1.51, P < 0.001), DN (SMD 1.50, 95% CI 1.19-1.80, P < 0.001), and combined DR plus DN (SMD 1.60, 95% CI 0.41-2.78, P = 0.008). Interleukin-6 and hsCRP/CRP showed similar elevations across groups, with statistically significant differences compared with controls.

MicroRNA expression was reduced in patients with microvascular complications. miR-126 was downregulated in DR (SMD −1.87, 95% CI −3.56 to −0.18, P = 0.03) and DN (SMD −0.36, 95% CI −0.54 to −0.18, P = 0.0001). miR-29b was also reduced in DR (SMD −0.47, 95% CI −0.51 to −0.43, P < 0.0001). Sensitivity analyses confirmed result stability, and Egger’s test showed no significant publication bias.

These findings indicate that inflammatory and microRNA dysregulation is more pronounced when DR and DN occur together, consistent with a synergistic pathogenic relationship in diabetic microvascular disease.

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Key highlights
  • Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity or standard C-reactive protein (hsCRP/CRP) were elevated in diabetic retinopathy (DR), diabetic nephropathy (DN), and combined DR plus DN.
  • MicroRNA-126 (miR-126) and microRNA-29b (miR-29b) were consistently downregulated across patient groups.
  • TNF-α levels were highest in patients with concurrent DR and DN, suggesting amplified inflammatory activity.
  • Biomarker patterns support a shared pathogenic axis in diabetic microvascular disease.
Source

Wang P, Wen Y. The inflammatory–miRNA axis in diabetes microvascular complications: a meta-analysis highlighting synergistic effects in concurrent retinopathy and nephropathy. J Diabetes Metab Disord. 2025;24:290. doi:10.1007/s40200-025-01809-z

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Concurrent Diabetic Retinopathy and Nephropathy Show Amplified Biomarker Dysregulation
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Inflammatory and microRNA alterations are more pronounced when diabetic microvascular complications coexist 
 

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