Abstract
INTRODUCTION: Environmental exposure to metals may play a role in the pathogenesis of diabetes; however, evidence from human studies is limited. We prospectively evaluated the associations of 20 urinary metal concentrations and their mixtures with incident diabetes in the Study of Women's Health Across the Nation, a multisite, multiethnic cohort study of midlife women. RESEARCH DESIGN AND METHODS: The sample included 1237 white, black, Chinese and Japanese-American women, aged 45-56 years, free of diabetes at baseline (1999-2000) who were followed through 2016. Concentrations of 20 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) were measured in urine specimens at baseline. Incident diabetes was identified annually by fasting glucose ≥126 mg/dL, self-reported doctor-diagnosed diabetes, or self-reported use of antidiabetic medications. A non-parametric clustering method, k-means clustering, was used to identify subgroups with different exposure patterns to metal mixtures. RESULTS: After multivariable adjustment, the HR (95% CI) for diabetes associated with each doubling increase in urinary metal concentrations was 1.19 (1.10 to 1.30) for arsenic and 1.20 (1.05 to 1.37) for lead, in Cox proportional hazards models after controlling for multiple comparisons. A doubling in urinary excretion of zinc was associated with higher risk of diabetes (adjusted HR 1.31, 95% CI 1.11 to 1.53). Two distinct exposure patterns to metal mixtures-'high' versus 'low'-were identified. Participants assigned to the 'high' pattern had higher overall concentrations of all metals compared with those classified into the 'low' pattern. Adjusted HR for diabetes associated with 'high' pattern compared with 'low' was 1.42 (1.08 to 1.87). CONCLUSIONS: Higher urinary concentrations of arsenic and lead, increased urinary excretion of zinc, as well as higher overall exposure to metal mixtures were associated with elevated risk of diabetes. Future studies should further investigate the underlying mechanisms.