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. 2018 Aug 1;187(8):1598-1612.
doi: 10.1093/aje/kwy048.

The Association of Arsenic Exposure and Arsenic Metabolism With the Metabolic Syndrome and Its Individual Components: Prospective Evidence From the Strong Heart Family Study

Miranda J Spratlen  1   2 , Maria Grau-Perez  3   4 , Lyle G Best  5 , Joseph Yracheta  5 , Mariana Lazo  6   7 , Dhananjay Vaidya  6   7 , Poojitha Balakrishnan  2 , Mary V Gamble  2 , Kevin A Francesconi  8 , Walter Goessler  8 , Shelley A Cole  9 , Jason G Umans  10   11 , Barbara V Howard  10   11 , Ana Navas-Acien  1   2
Affiliations

The Association of Arsenic Exposure and Arsenic Metabolism With the Metabolic Syndrome and Its Individual Components: Prospective Evidence From the Strong Heart Family Study

Miranda J Spratlen et al. Am J Epidemiol. .

Abstract

Inorganic arsenic exposure is ubiquitous, and both exposure and interindividual differences in its metabolism have been associated with cardiometabolic risk. However, the associations of arsenic exposure and arsenic metabolism with the metabolic syndrome (MetS) and its individual components are relatively unknown. We used Poisson regression with robust variance to evaluate the associations of baseline arsenic exposure (urinary arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident MetS and its individual components (elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, hypertension, and elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort study in American Indian communities (baseline visits were held in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). Over the course of follow-up, 32% of participants developed MetS. An interquartile-range increase in arsenic exposure was associated with a 1.19-fold (95% confidence interval: 1.01, 1.41) greater risk of elevated fasting plasma glucose concentration but not with other individual components of the MetS or MetS overall. Arsenic metabolism, specifically lower percentage of monomethylarsonic acid and higher percentage of dimethylarsinic acid, was associated with higher risk of overall MetS and elevated waist circumference but not with any other MetS component. These findings support the hypothesis that there are contrasting and independent associations of arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

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Figures

Figure 1.
Figure 1.
Selection of study participants for an analysis of the associations between arsenic exposure and the metabolic syndrome (MetS) and its components (elevated waist circumference (WC), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), hypertension (HT), and elevated fasting plasma glucose (FPG)), Strong Heart Family Study, 1998–2003.
Figure 2.
Figure 2.
Relative risk of the metabolic syndrome and its individual components according to the sum of inorganic and methylated arsenic species (∑As), Strong Heart Family Study, 1998–2009. ∑As was calculated as the sum of urinary inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid concentrations. The solid black lines represent adjusted relative risks of: incident metabolic syndrome, defined as meeting 3 or more of the individual criteria (A); elevated waist circumference, defined as ≥40 inches (≥102 cm) in men and ≥35 inches (≥89 cm) in women (B); elevated triglyceride level, defined as ≥150 mg/dL (or use of medication) (C); reduced high-density lipoprotein cholesterol level, defined as <40 mg/dL for men and <50 mg/dL for women (or use of medication) (D); hypertension, defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg (or use of medication) (E); and elevated fasting plasma glucose level, defined as ≥100 mg/dL (or use of medication) (F). Relative risks were calculated using restricted cubic splines for ∑As with knots at the 10th, 50th, and 90th percentiles of the ∑As distribution and were adjusted for log urinary creatinine, age, sex, body mass index (excluding waist circumference models), educational level, region (Arizona, Oklahoma, or North/South Dakota), smoking status, alcohol intake, and kidney function. The referent was set at the 10th percentile of the ∑As distribution. Dotted lines show 95% confidence intervals. Histograms represent the distribution of log-transformed ∑As values.
Figure 3.
Figure 3.
Relative risk of the metabolic syndrome (MetS) and its individual components according to the sum of inorganic and methylated arsenic species (∑As) and per 5% increase in biomarkers of arsenic metabolism, Strong Heart Family Study, 1998–2009. ∑As was calculated as the sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations. Part A shows the relative risk of incident MetS and its individual components (elevated waist circumference (WC; ≥40 inches (≥102 cm) in men and ≥35 inches (≥89 cm) in women), elevated triglyceride (TG) level (≥150 mg/dL (or use of medication)), reduced high-density lipoprotein (HDL) cholesterol level (<40 mg/dL for men and <50 mg/dL for women (or use of medication)), hypertension (HT; systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg (or use of medication)), and elevated fasting plasma glucose (FPG) level (≥100 mg/dL (or use of medication)) per interquartile-range increase in ∑As. Points (●) represent relative risk, and vertical lines represent 95% confidence intervals. Parts B–D show the relative risk of MetS and its individual components per 5% increase in percentage of iAs (B), percentage of MMA (C), and percentage of DMA (D). The 3 different types of points in panels B–D reflect the 3 different models used to estimate relative risk: the conventional model (■) and 2 leave-one-out (LOO) models (● and ▲). Relative risks were adjusted for log ∑As (excluding exposure models), log urinary creatinine, age, sex, body mass index (excluding waist circumference models), educational level, region (Arizona, Oklahoma, or North/South Dakota), smoking status, alcohol intake, and kidney function.
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References

    1. Aguilar M, Bhuket T, Torres S, et al. . Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA. 2015;313(19):1973–1974. - PubMed
    1. Alberti GZ, Shaw J, Grundy SM. The IDF Consensus Worldwide Definition of the Metabolic Syndrome Brussels, Belgium: International Diabetes Federation; 2006. https://www.idf.org/e-library/consensus-statements/60-idfconsensus-world.... Accessed May 2, 2018.
    1. Grundy SM, Cleeman JI, Daniels SR, et al. . Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–2752. - PubMed
    1. Stern MP, Williams K, González-Villalpando C, et al. . Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care. 2004;27(11):2676–2681. - PubMed
    1. Paul DS, Hernández-Zavala A, Walton FS, et al. . Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: development of a mouse model for arsenic-induced diabetes. Toxicol Appl Pharmacol. 2007;222(3):305–314. - PMC - PubMed

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