Climate change and air pollution can amplify vulnerability of glucose metabolism: The mediating effects of biological aging.

Climate change and air pollution pose significant global health threats, including impacts on diabetes risk; however, their long-term effects on insulin resistance (IR), a key determinant in diabetes pathophysiology, remain unclear. This study investigated whether exposure to heatwaves, temperature fluctuations, and warm-season ozone (O3) contributes to or exacerbates IR and explored the potential mediating role of biological aging. The study enrolled 6901 participants and assessed both traditional and novel IR indicators: estimated glucose disposal rate (eGDR), triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c), metabolic score for IR (METS-IR), TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), waist-to-height ratio (WHtR), TyG-WHtR, and lipid accumulation product (LAP). Ordinary least squares regression models were applied to evaluate the long-lasting effects of heatwaves, temperature fluctuation, and warm-season O3 on IR, incorporating Huber-White robust standard errors for model stability. Causal mediation analysis was utilized to investigate the mediating effects of biological aging. We found that exposure to heatwaves and higher concentrations of warm-season O3 was associated with elevated IR levels, with males, smokers, drinkers, and low-income individuals being more vulnerable. Accelerated biological aging (including body age, metabolomic aging rate, etc.) could significant mediate the long-lasting effects of heatwaves and warm-season O3. Our findings suggest that climate change and air pollution could amplify the vulnerability of glucose metabolism, particularly in males, smokers, drinkers, and individuals with low-income. More importantly, our findings reveal the importance of mitigating biological aging to prevent IR in the future, as global diabetes prevalence escalates rapidly.