Dataset Information

Urinary metal mixtures and longitudinal changes in glucose homeostasis: The Study of Women's Health Across the Nation (SWAN).

ABSTRACT:

Background

Epidemiologic studies on associations between metals and insulin resistance and β-cell dysfunction have been cross-sectional and focused on individual metals.

Objective

We assessed the association of exposure to metal mixtures, based on assessment of 15 urinary metals, with both baseline levels and longitudinal changes in homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-β).

Methods

We examined 1262 women, aged 45-56 years at baseline (1999-2000), who were followed through 2015-2016, from the Study of Women's Health Across the Nation. Urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined at baseline. HOMA-IR and HOMA-β were repeatedly measured over 16 years of follow-up. A two-stage modeling was used to account for correlations in dependent and independent variables: In stage-1, linear mixed effects models were used to estimate the participant-specific baseline HOMA levels from random intercepts and participant-specific rates of changes from random slopes. In stage-2, adaptive elastic-net (AENET) models were fit to identify components of metal mixtures associated with participant-specific baseline levels and rates of changes in HOMA-IR and HOMA-β, respectively. An environmental risk score (ERS) was used to integrate metal mixture effects from AENET results.

Results

In multivariable adjusted AENET models, urinary zinc was associated with higher HOMA-IR at baseline, whereas molybdenum was associated with lower HOMA-IR at baseline. The estimated changes in baseline HOMA-IR for one standard deviation increase in log-transformed urinary metal concentrations were 5.76% (3.05%, 8.55%) for zinc and -3.25% (-5.45%, -1.00%) for molybdenum, respectively. Urinary zinc was also associated with lower HOMA- β at baseline. Arsenic was associated with a slightly faster rate of decline in HOMA-β in the AENET model evaluating associations between metals and rate of changes. Significant associations of ERS with both HOMA-IR and HOMA-β at baseline were observed. ERS for the rate of changes was not calculated and examined in relation to rates of changes in HOMA-IR and HOMA-β because only a single metal was selected by AENET.

Conclusion

Exposure to metal mixtures may be exerting effects on insulin resistance and β-cell dysfunction, which might be mechanisms by which metal exposures lead to elevated diabetes risks.

SUBMITTER: Wang X

PROVIDER: S-EPMC7577932 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Little is known about the extent of exposure to metals and metal mixtures among midlife women. OBJECTIVES:We assessed exposure to multiple metals in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-racial/ethnic cohort of women at midlife. METHODS:We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) using high-resolution inductively coupled plasma-mass spectrometry among 1335 white, black, Chinese and Japanese women aged 45-56?years?at the third SWAN annual visit (1999-2000). Least squared geometric mean concentrations were compared across race/ethnicity, education, financial hardship, smoking, secondhand smoking, seafood intake and rice intake groups. Overall exposure patterns of multiple metals were derived using k-means clustering method. RESULTS:The percentage of women with detectable concentrations of metals ranged from 100% for arsenic, cesium, molybdenum and zinc, to less than 5% for platinum; 15 metals had detection rates of 70% or more. Asian women, both Chinese and Japanese, had higher urinary concentrations of arsenic, cadmium, copper, mercury, molybdenum, lead and thallium, compared with other race/ethnic groups, independent of sociodemographic, lifestyle, dietary, and geographic characteristics. Seafood and rice intake were important determinants of urinary arsenic, cesium, mercury, molybdenum and lead levels. Two distinct overall exposure patterns- "high" vs. "low" -- were identified. Women in the "high" overall exposure pattern were more likely to be Asians, current smokers, and to report high consumption of seafood and rice. Black women were less likely to have the high exposure pattern. CONCLUSIONS:Metal exposure of midlife women differs by racial/ethnic, sociodemographic, lifestyle, dietary, and geographic characteristics. Asian women may be experiencing the highest exposures to multiple metals compared with other racial/ethnic groups in the United States.

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