Associations between dose-response of serum creatinine and type 2 diabetes mellitus risk: consistent and robust evidence from a systematic review and meta-analysis.

Background: Skeletal muscle is the key target of insulin action. Therefore, a reduction in skeletal muscle mass may trigger insulin resistance, a mechanism of diabetes. Creatinine is the only metabolite of creatine phosphate in the skeletal muscle. Exploring the association between serum creatinine level and T2DM is helpful for the early identification and prevention of T2DM.

Research design and methods: Five electronic databases, PubMed, Scopus, Web of Science, Embase, and Epistemonikos, were searched for relevant articles published up to June 2024. Cohort studies and case-control studies were evaluated using the Joanna Briggs Institute (JBI) checklist. The random-effects model calculated the pooled risk ratio and 95% confidence intervals (CIs) based on a heterogeneity test (I² statistics). Egger's test was used to evaluate publication bias.

Results: The pooled RR of diabetes type 2 for the lowest versus the highest serum creatinine was 1.39 (95% CI: 1.17-1.64); I² = 90.1%; p = 0.002. We found a non-linear association between low serum creatinine level and T2DM risk (p_Nonlinearity = 0.02), and a decrease of each 0.1 mg/dL serum creatinine increases 1% risk of T2DM [RR = 1.49 (95% CI: 1.17-2.82), I² = 0%, p = 0.999].

Conclusions: This meta-analysis offers evidence of the negative relationship between serum creatinine levels and the risk of developing T2DM in a linear dose-response pattern.