Fasting plasma metabolites reflecting meat consumption and their associations with incident type 2 diabetes in two Swedish cohorts

Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers. To investigate metabolite biomarkers of meat intake and their associations with T2D risk. Fasting plasma samples were collected from a case-control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed and unprocessed red meat, and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n=4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts. In total, 15 metabolites were associated with at least one meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake (r>0.22, FDR<0.001 for VIP and r>0.05, FDR <0.001 for SMCC) were consistently associated with higher T2D risk in both datasets. Conversely, lysophosphatidylcholine (LPC) 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < -0.12, FDR <0.023 for VIP and r < -0.05, FDR<0.001 for SMCC) and with lower T2D risk in both datasets, except for PC 15:0/18:2 which was significant only in VIP. All associations were attenuated after adjustment for BMI. Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.