Associations between serum persistent organic pollutants and type 2 diabetes in a multipollutant analysis using repeated measurements in the Tromsø Study

Introduction Persistent organic pollutants (POPs) occur as correlated mixtures, and serum concentrations may vary over time due to changes in exposure and toxicokinetic processes. We investigated associations between a mixture of POPs measured repeatedly before type 2 diabetes mellitus diagnosis (T2DM). Material and methods In a longitudinal nested case-control study within the Tromsø Study, serum concentrations of 19 chlorinated POPs were measured at three pre-diagnostic timepoints: T1 (1986/87; 15–21 years before diagnosis, n = 259), T2 (1994/95; 7–13 years before diagnosis, n = 257), and T3 (2001; 0–6 years before diagnosis, n = 260). Lipid-adjusted POP concentrations were analyzed using positive-direction weighted quantile sum (WQS) logistic regression. Single-pollutant analyses were conducted for comparison. Results The POP mixture was positively associated with subsequent T2DM at T2 [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.34–3.42] and T3 (OR 1.78, 95% CI 1.19–2.66), whereas no association was detected at T1. Cis -heptachlor epoxide and p,p' -DDT received the largest weights at T2. At T3, weights were more distributed, with cis -nonachlor, cis- heptachlor epoxide, β -HCH, PCB-194, and PCB-187 exceeding the equal-weight threshold. Single-pollutant analyses identified similar leading compounds at T2 and T3. Conclusion POP mixtures measured at T2 and T3 were positively associated with subsequent T2DM. These associations may partly reflect preclinical metabolic changes, altered POPs distribution between adipose tissue and blood, residual confounding, or chance. The findings support the complementary use of mixture and single-pollutant approaches and the value of repeated POP measurements. Larger longitudinal studies are needed to clarify temporality, evaluate potential reverse causation, and formally assess time-varying mixture associations.