The modifiable effect of vitamin D in the association between long-term exposure to ambient air pollution and glycosylated hemoglobin in patients with hypertension

Objectives: Evidence on the association between long-term exposure to ambient air pollution and serum glycosylated hemoglobin A_1c (HbA_1c) is limited and inconclusive. In addition, whether vitamin D can modify the association between air pollution exposure and glucose metabolism has not been previously investigated. We aimed to evaluate the effects of various air pollutants on serum HbA_1c levels in patients with hypertension and, further, to explore the modification effect of individual serum vitamin D levels.

Methods: This study was derived from UK Biobank study, and 246 027 participants with hypertension were included in our analysis. Individual exposures to particulate matters (PMs) and nitrogen oxides were estimated using the land use regression model. The associations between air pollutants and HbA_1c were assessed using the multivariable linear regression model. Among the 222 845 participants with a measurement of serum vitamin D, we explored the associations in subgroups stratified by vitamin D levels.

Results: Long-term air pollutant exposures were significantly associated with higher HbA_1c levels. After adjusting for potential confounders, 10-μg/m³ (or 1-m^-1) increases in concentrations of PM with diameters ≤2.5 µm (PM_2.5), PM with diameters ≤10 µm, PM with diameters from 2.5 µm to 10 µm, PM_2.5 absorbance, nitrogen oxides, and nitrogen dioxide were significantly associated with 0.59 (95% confidence interval, 0.28-0.89), 0.49 (0.33-0.65), 0.81 (0.48-1.14), 0.56 (0.44-0.69), 0.06 (0.04-0.09), and 0.16 (0.12-0.21) mmol/mol increase in serum HbA_1c levels, respectively. The associations were weakened but remained significant after additional adjustment of vitamin D. In addition, the associations of air pollutants with HbA_1c were more evident in participants with low serum vitamin D levels (all P values for interaction <0.001).

Conclusions: Long-term exposures to ambient air pollutants were associated with higher levels of HbA_1c in a dose-response fashion in a large UK cohort. Serum vitamin D status significantly modified these associations, and high serum vitamin D levels may attenuate the relationships between air pollution exposures and HbA_1c levels.