Acrylamide Exposure and Type 2 Diabetes in a Prospective Cohort Study of Chinese Adults: Association, Mediation, and Gene–Environment Interaction

The health risks of acrylamide have attracted global attention, given lifelong exposure of people to this world-shocking chemical from daily life, especially from food consumed daily. Responding to the World Health Organization's call for more and exigent research on health risks from acrylamide, this prospective cohort study of 3522 Chinese adults with 3-year follow-up intends to illuminate whether and how acrylamide is associated with type 2 diabetes (T2D) risk. Participants with Consistent-High (vs Consistent-Low) levels of acrylamide exposure biomarkers (repeatedly measured at baseline and 3-year follow-up) prospectively showed 139%-162% (risk ratio: 2.39-2.62; <i>P</i> < 0.05) T2D risk elevation. Exhaled carbon monoxide, a heme oxygenase-1 (HO-1) activity biomarker indicative of oxidative stress, mediated 11.07%-11.54% of the acrylamide-T2D associations, while no other oxidative stress or inflammation indicators measured (<i>N</i> = 7) showed evidence of mediation. Multiplicative (<i>P</i>_interaction < 0.05) and additive (relative excess risk due to interaction: 1.42-2.07; <i>P</i> < 0.05) interactions between the T2D polygenic risk score and acrylamide exposure biomarkers on incident T2D were discovered. Conclusively, acrylamide exposure was associated with elevated T2D risk, partly mediated by HO-1 activation and interactively aggravated by T2D genetic susceptibility, underscoring the global public health concern on the T2D risk of acrylamide exposure (especially among individuals with high T2D genetic risk) with critical involvement of HO-1 activation.