Remarkably, our urinary signature for early diabetes includes a core protein of the keratan sulfate proteoglycan (lumican) and the complete set of putative enzymes that break down keratan sulfate (GALNS, GLB1, GNS, HEXA, and HEXB), which were all excreted to a greater extent by youths with type 1 diabetes, compared to their non-diabetic peers and were strongly correlated with one another. Here, HEXB is linked to type 1 diabetes mellitus.