OBJECTIVES: We aimed to evaluate the associations of hexosylceramides (HexCers) and their ratio with incident type 2 diabetes mellitus (T2DM) and explore underlying mechanisms. METHODS: We conducted a nested case-control study using the Suzhou chronic disease cohort including 234 T2DM cases and 468 controls, 1:2 matched on age (±2 y) and sex. HexCer(d18:1/16:1) and HexCer(d18:1/24:1) were measured by targeted UPLC-MS/MS. Multivariable conditional logistic regression was used to estimate the associations of these HexCer species and their ratio with T2DM risk. RESULTS: After adjustment for potential confounders, compared with the lowest quartile, the highest quartile of HexCer(d18:1/24:1) was positively associated with T2DM risk (OR: 1.91
95%CI, 1.12, 3.26
CONCLUSIONS: HexCer(d18:1/24:1) and its ratio to HexCer(d18:1/16:1) are positively associated with incident T2DM in a community-based Chinese population. Future studies are warranted to confirm our findings.