Exploring Biomarkers in Type 2 Diabetes Mellitus versus Normoglycemia Identified through High-Throughput Proteomics: A Systematic Review and Meta-Analysis

Recent advances in proteomics have enabled the identification
of
early protein biomarkers and metabolic disturbances associated with
type 2 diabetes (T2D), a major global health challenge. This systematic
review and meta-analysis synthesize evidence from 27 studies comparing
proteomic profiles of individuals with T2D and normoglycemic controls,
selected from 2,422 initial records. The QUADOMICS assessment showed
good methodological reporting for sample handling and proteomic analysis
(>70% of studies), but over 60% lacked information on confounding
clinical factors and biomarker validation. A qualitative synthesis
focused on 85 recurrently reported proteins (≥8 studies), which
showed strong interconnectivity and were involved in immune response,
lipid–protein organization, detoxification, proteolysis, and
coagulation, key pathways implicated in T2D. An omics-based meta-analysis
identified seven promising protein biomarkers for T2D related to lipid/glucose
metabolism (Q12907_LMAN2, P02652_POA2, P07602_PSPA, P09622_DLD); cell
binding/adhesion (P12109_COL6A1, P12830_CDH1); and translational regulation
and mitochondrial function (P35232_PHB). Random-effects meta-analysis
revealed variation in effect sizes across studies for previously highlighted
biomarkers, but three of them (P02763_ORM1, P00738_HP, P25311_AZGP1)
exhibited considerable consistency. To enhance accessibility and further
exploration of findings, we provide the interactive web tool metaMarkersT2D: https://jgcurras.shinyapps.io/metaMarkersT2D/.