Using genetic information, we found that T2DM risk was associated with decreased expression of XBP1. An eQTL for XBP1 reported in pancreatic islets and beta-cells (rs728712(A > G)) was also associated with lower beta-cell function using HOMA-B and higher stimulated glucose in Asian Indians with newly-diagnosed T2DM. Here, XBP1 is linked to type 2 diabetes mellitus.