eGDR and gastrointestinal cancer mortality in the UK Biobank: a prospective cohort study

BACKGROUND: This study examined the associations of estimated glucose disposal rate (eGDR), a surrogate of insulin sensitivity, and the insulin resistance indices TG/HDL-C and TyG with gastrointestinal (GI) cancer mortality in the UK Biobank. METHODS: We included 369,447 participants without cancer at baseline and recorded 4,305 GI cancer-related deaths over a mean follow-up of 13.5 years. Fine-Gray models assessed associations of eGDR, TG/HDL-C, and TyG with GI cancer mortality. RESULTS: Higher eGDR was associated with lower pooled GI cancer mortality (sHR, 0.67; 95% CI, 0.61-0.74; P < 0.001); associations with EC, ESCC, CRC, LC, and PC mortality remained significant after false discovery rate (FDR) correction. TyG, but not TG/HDL-C, remained associated with pooled GI cancer mortality, and both markers remained associated with LC mortality. Subgroup analyses were exploratory. CONCLUSIONS: Higher eGDR was associated with lower pooled and several site-specific GI cancer mortality outcomes, whereas TG/HDL-C and TyG associations were modest and site-specific. These findings do not establish clinical utility.