Serum Proteomics of Early Diabetic Nephropathy Biomarkers in Type 2 Diabetic Patients in Oyo State, South West Nigeria: A Gel-Based Analysis

Conventional biomarkers such as microalbuminuria lack the sensitivity to detect the earliest molecular changes in diabetic nephropathy, creating a research gap that proteomics-based discovery approaches can address by identifying novel protein signatures. This study applied gel-based serum proteomics to identify early diabetic nephropathy biomarkers in type 2 diabetic patients at University College Hospital Ibadan, Oyo State, South West Nigeria. A case-control design enrolled 30 type 2 diabetic patients with normoalbuminuria, 30 with microalbuminuria, and 30 healthy controls. Serum was subjected to albumin and IgG depletion, two-dimensional polyacrylamide gel electrophoresis, and differentially expressed protein spots were identified by MALDI-TOF/TOF mass spectrometry. Bioinformatic pathway analysis was performed using STRING and KEGG databases. Sixteen proteins were differentially expressed between normoalbuminuric diabetics and controls. Among these, complement component C3, alpha-1-antitrypsin, and apolipoprotein A-I were downregulated, while fibronectin and transferrin were upregulated in early stages. The microalbuminuric group showed further dysregulation of complement and coagulation pathways. Receiver operating characteristic analysis identified a three-protein panel with AUC of 0.86 for distinguishing early nephropathy from normoalbuminuria. The study identifies candidate serum protein biomarkers for early diabetic nephropathy detection in Nigerian patients and recommends validation in a larger prospective cohort using targeted mass spectrometry to establish clinical utility before translation to diagnostic assay development. Keywords: proteomics, diabetic nephropathy, biomarkers, MALDI-TOF, type 2 diabetes