α2-macroglobulin, cathepsin D, and CD324 are protein DKD progression biomarkers. Galactose and glycerolipid metabolism majorly disturbed in DKD, with glycerol-3-galactoside useful in predicting DKD pathogenesis. Integrating proteomic and metabolomic data improved DKD prediction models. This evidence concerns the gene CTSD and diabetic kidney disease.