Pesticides associated with incident diabetes among licensed private pesticide applicators in the Agricultural Health Study cohort (1993-2021).

Growing evidence suggests pesticides may increase risk of type 2 diabetes, but data are limited on many specific chemicals. In 29,527 private pesticide applicators in the Agricultural Health Study cohort (enrolled 1993-1997 in Iowa and North Carolina), 3,847 incident diabetes cases were identified by self-report during follow-up surveys in 1999-2003, 2005-2010, 2013-2015, and 2019-2021. We examined 50 pesticides reported at enrollment, updated in 1999-2003 or 2005-2010, prior to diabetes diagnosis or end of follow-up, using log-binomial regression to calculate relative risks (RR) and 95% confidence intervals (CI) for ever-use and intensity-weighted lifetime days (IWLD) use (tertiles, T1-3), adjusting for covariates and correlated pesticides. Greater diabetes risk was associated with 7 organochlorine insecticides: ever-use of DDT, aldrin, dieldrin, chlordane, heptachlor, and toxaphene (RRs 1.08-1.31), without monotonic exposure-response trends, and lower IWLD of lindane use (T1RR=1.32; 95%CI 1.12-1.57). Risk was associated with 5 organophosphate or carbamate insecticides: ever-use of diazinon and carbofuran, and exposure-response trends for malathion (T3RR=1.13;95%CI 1.02-1.25, p-trend=0.025), phorate (T3RR=1.22;95%CI 1.08-1.39, p-trend=0.001), and carbaryl (T3RR=1.26;95%CI 1.11-1.43, p-trend=0.005). Risk was associated with 2 phenoxy herbicides, 2,4,5-T (ever-use RR=1.25;95%CI 1.14-1.37) and 2,4,5-TP (T1RR=1.35;95%CI 1.04-1.76), and 3 other herbicides [butylate (T3RR=1.26;95%CI 1.10-1.44, p-trend<0.001), metribuzin (T3RR=1.16;95%CI 1.16-1.32, p-trend=0.022), chlorimuron ethyl (T3RR=1.16;95%CI 1.02-1.31, p-trend=0.033)], and the fumigant carbon tetrachloride/disulfide (RR=1.16;95%CI 1.02-1.33). Associations were not confounded by BMI and weight gain. These results show greater diabetes risk associated with use of persistent organochlorine insecticides and banned phenoxy herbicides. Novel findings for widely used insecticides and other pesticides warrant further investigation.