Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures
Bin Wang, Wei Liu, Linling Yu, Zi Ye, Man Cheng, Weihong Qiu, Min Zhou, Jixuan Ma, Xing Wang, Meng Yang, Jiahao Song, Weihong Chen
Abstract
Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites ( N -acetyl- S -(3-hydroxypropyl)- l -cysteine, N -acetyl- S -(2-carboxyethyl)- l -cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91–6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07–0.14 mmol/L, 4.02–4.57, 5.91–6.52, 19–20, 18–19, and 23–31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63–80, 87–99, and 120–154%, respectively ( P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00–38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.