Circulating organochlorine pesticide levels, genetic predisposition and the risk of incident type 2 diabetes.

Persistent organochlorine pesticide (OCP) has been associated with type 2 diabetes (T2D), and genetic polymorphism might modify such an association. However, prospective evidence remains scarce. We conducted a nested case-control study comprising 1006 incident diabetic cases and 1006 matched non-diabetic controls [sex and age (±5 years)] from 2008 to 2013 (mean follow-up period: ∼4.6 years) based on the Dongfeng-Tongji cohort in Shiyan City of China, determined baseline levels of nineteen OCPs, and examined the associations of circulating OCPs, both individually and collectively, with incident T2D risk. We also constructed overall genetic risk score (GRS) based on 161 T2D-associated variants and five pathway-specific cluster GRSs based on established variants derived from the Asian population. Compared with the first quartile of serum β-BHC levels, the multivariable-adjusted ORs (95% CIs) of incident T2D risk in the second, third, and fourth quartiles were 0.98 (0.70-1.39), 1.43 (0.99-2.07), and 1.75 (1.14-2.68), respectively (FDR-adjusted P = 0.03). A positive association was observed between serum OCP mixture and incident T2D risk and can be largely attributed to β-BHC. Furthermore, serum β-BHC and p,p'-DDE showed significant interactions with the GRS for lipodystrophy, a T2D-related pathway representing fat redistribution to viscera, on T2D risk (P < 0.05). In conclusion, higher circulating OCP levels were independently associated with an increased risk of T2D, with β-BHC possibly being the major contributor. Genetic predisposition to T2D-related morbidity, such as visceral adiposity, should be considered when assessing the risk of T2D conferred by OCPs.