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Aim <p>Diabetic kidney disease (DKD) is a severe complication of diabetes, with early detection crucial for preventing irreversible kidney damage. Despite numerous DKD metabolite profiling studies, results remain inconsistent. This meta-analysis aims to identify consensus dysregulated metabolites as potential biomarkers for Type 2 diabetes (T2D)-induced DKD.</p> Materials and methods <p>Following PRISMA guidelines, a systematic review from 2014 to 2024 included human studies of T2D and DKD. Quality assessment employed the Newcastle-Ottawa Scale (NOS). Bubble plots determined predominant metabolite classes. MetaboAnalyst 5.0 facilitated pathway and enrichment analysis, while RevMan v5.4 performed meta-analysis.</p> Results <p>Amino acids were the most studied metabolite class in both T2D and DKD. Enrichment analysis highlighted glycine and serine metabolism; phenylalanine and tyrosine metabolism; and methionine metabolism as dominant pathways. Meta-analysis revealed low ornithine (-0.50 [-0.91, -0.10], <i>p</i> = 0.01) and high isoleucine (0.76[0.50, 1.03], <i>p</i> &lt; 0.00001) concentrations associated with T2D. Conversely, lower methionine (-0.32 [-0.57, -0.08), <i>p</i> = 0.01), tyrosine (-0.73 [-1.28, -0.17], <i>p</i> = 0.01), and valine (-2.32 [-2.99, -1.66], <i>p</i> = 0.009) levels were associated with DKD. Correlation analysis revealed associations between phenylalanine, tyrosine, and serine with albumin and creatinine levels in T2D but not in DKD.</p> Conclusions <p>These identified metabolites hold potential as early markers for T2D-induced DKD. However, the use of these metabolites for clinical purposes requires experimental validation and clinical trials.</p>

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Metabolomics approaches for the early detection and therapeutics: type 2 diabetes-induced diabetic kidney disease—a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2025年11月1日

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  • Gnanasambandan Ramanathan,
  • Sivaraman Dhanasekaran,
  • Aalaya Haridas

摘要

Aim

Diabetic kidney disease (DKD) is a severe complication of diabetes, with early detection crucial for preventing irreversible kidney damage. Despite numerous DKD metabolite profiling studies, results remain inconsistent. This meta-analysis aims to identify consensus dysregulated metabolites as potential biomarkers for Type 2 diabetes (T2D)-induced DKD.

Materials and methods

Following PRISMA guidelines, a systematic review from 2014 to 2024 included human studies of T2D and DKD. Quality assessment employed the Newcastle-Ottawa Scale (NOS). Bubble plots determined predominant metabolite classes. MetaboAnalyst 5.0 facilitated pathway and enrichment analysis, while RevMan v5.4 performed meta-analysis.

Results

Amino acids were the most studied metabolite class in both T2D and DKD. Enrichment analysis highlighted glycine and serine metabolism; phenylalanine and tyrosine metabolism; and methionine metabolism as dominant pathways. Meta-analysis revealed low ornithine (-0.50 [-0.91, -0.10], p = 0.01) and high isoleucine (0.76[0.50, 1.03], p < 0.00001) concentrations associated with T2D. Conversely, lower methionine (-0.32 [-0.57, -0.08), p = 0.01), tyrosine (-0.73 [-1.28, -0.17], p = 0.01), and valine (-2.32 [-2.99, -1.66], p = 0.009) levels were associated with DKD. Correlation analysis revealed associations between phenylalanine, tyrosine, and serine with albumin and creatinine levels in T2D but not in DKD.

Conclusions

These identified metabolites hold potential as early markers for T2D-induced DKD. However, the use of these metabolites for clinical purposes requires experimental validation and clinical trials.