Urinary Metals and Incident Diabetes in Midlife Women: Study of Women’s Health Across the Nation (SWAN)

Abstract

Background: 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 multi-site, multi-ethnic cohort study of midlife women. Methods: The sample included 1,226 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 using high-resolution inductively coupled plasma-mass spectrometry at baseline. Incident diabetes was identified annually. Exposure to metal mixtures were captured using k-means clustering. Results: After multivariable adjustment, the hazard ratios (HR) (95% CI) of diabetes associated with each doubling increase in urinary metal concentrations were 1.13 (1.04, 1.23) for arsenic and 1.22 (1.09, 1.37) for lead, in Cox proportional hazards models after controlling for multiple comparison. A doubling in urinary excretion of zinc was associated with higher diabetes risk (adjusted HR 1.47, 95% CI: 1.27, 1.70). Two distinct exposure patterns to metal mixtures- “high” vs. “low”-were identified. Adjusted HR of diabetes associated with “high” exposure pattern compared with “low” was 1.38 (1.09, 1.75). Conclusions: Exposure to arsenic and lead, an increase urinary excretion of zinc, as well as a high overall exposure to metal mixtures were associated with elevated diabetes risks. Future studies should further investigate the underlying mechanisms by which metals may influence diabetes.