Roshan Kumar Mahat, Mritunjay Kumar Mishra, Nand Kishor Prasad Sah, Sushil Yadav
Circulating calprotectin is elevated in T2DM, supporting its role as a biomarker of metabolic inflammation. Associations with neuropathy and macrovascular disease are suggestive but heterogeneous, while evidence for urinary calprotectin remains inconclusive.
BACKGROUND: Calprotectin is a myeloid-derived damage-associated molecular pattern implicated in metabolic inflammation and vascular injury. Evidence regarding circulating and urinary calprotectin in type 2 diabetes mellitus (T2DM) and its complications remains inconsistent.
METHODS: PubMed, Scopus, and Web of Science were searched up to 25th October 2025. Human observational studies reporting quantitative calprotectin levels were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I2 and Cochran's Q. Sensitivity analyses, prediction intervals, and publication bias evaluation using the Doi plot and LFK index were performed.
RESULTS: Seventeen studies were included in the metaanalysis. Circulating calprotectin levels were significantly higher in patients with T2DM compared with healthy controls (SMD = 1.08, 95% CI: 0.77-1.39; p < 0.0001; P = 78.2%). Sensitivity analyses confirmed the robustness of this association, although small-study effects were suggested. Higher circulating calprotectin levels were observed in T2DM patients with peripheral neuropathy (SMD = 1.02; 95% CI: 0.06-1.98) and macrovascular complications (SMD = 0.43; 95% CI: 0.08-0.77) compared with those without complications, but these associations showed considerable heterogeneity and limited stability. No significant difference in circulating calprotectin levels was observed between T2DM patients with microalbuminuria and normoalbuminuria. Urinary calprotectin levels did not differ significantly between T2DM patients and controls.
CONCLUSIONS: Circulating calprotectin is elevated in T2DM, supporting its role as a biomarker of metabolic inflammation. Associations with neuropathy and macrovascular disease are suggestive but heterogeneous, while evidence for urinary calprotectin remains inconclusive.