Urinary metals and incident diabetes in midlife women: Study of Women’s Health Across the Nation (SWAN)

Abstract

IntroductionEnvironmental 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 methodsThe 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.ResultsAfter 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).ConclusionsHigher 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.

Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats

“…The results obtained at the conditions studied were consistent with previous literature; the increase in urinary excretion of Zn but not Cu has previously been described [ 38 ]. Mn excretion in diabetic conditions is controversial because some authors showed that this disease increased its excretion [ 5 , 39 ], whereas others found no significant changes [ 38 ]. The high food intake could be associated with a significant increase in net mineral absorption and retention ( Table 1 ).…”

Effects of multi‐metal exposure on the risk of diabetes mellitus among people aged 40–75 years in rural areas in southwest China

“…A few prospective studies that explored the associations between metal exposure and diabetes mellitus presented the different roles of metals in diabetes mellitus development 15 , 17 , 25 , 26 , 27 , 28 , 29 , 30 . However, no unified conclusion about which metal is harmful, protective or irrelevant for diabetes mellitus has been achieved, partly because of the different metal mixture effects, implications of variable biological samples, times and levels of exposure in these studies.…”

“…Although several recent studies have explored the relationship between multi‐metal exposure and diabetes mellitus risk, their conclusions are inconsistent. Several population‐based epidemiological surveys from different regions have found that magnesium (Mg), calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), cadmium (Cd), copper (Cu) and lead (Pb) are associated with FBG or diabetes mellitus prevalence 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , whereas other studies have found no association 3 , 16 , 17 , 18 , 19 . Furthermore, the interaction of metals presents a challenge for correlation exploration.…”

Multipollutant, longitudinal analysis of the association between urinary tungsten and incident diabetes in a rural population

“… 44 Another prospective study conducted in US women did not find a significant association between urinary W and incident diabetes; however, this study used above or below the limit of detection as exposed or unexposed, respectively, and only 29% of participants had detectable W levels. 21 Thus, the differences in exposure assessment could explain the discrepancies in results.…”