Early-Life Arsenic Exposure, Nutritional Status, and Adult Diabetes Risk
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Purpose of Review
In utero influences, including nutrition and environmental chemicals, may induce long-term metabolic changes and increase diabetes risk in adulthood. This review evaluates the experimental and epidemiological evidence on the association of early-life arsenic exposure on diabetes and diabetes-related outcomes, as well as the influence of maternal nutritional status on arsenic-related metabolic effects.
Five studies in rodents have evaluated the role of in utero arsenic exposure with diabetes in the offspring. In four of the studies, elevated post-natal fasting glucose was observed when comparing in utero arsenic exposure with no exposure. Rodent offspring exposed to arsenic in utero also showed elevated insulin resistance in the 4 studies evaluating it as well as microRNA changes related to glycemic control in 2 studies. Birth cohorts of arsenic-exposed pregnant mothers in New Hampshire, Mexico, and Taiwan have shown that increased prenatal arsenic exposure is related to altered cord blood gene expression, microRNA, and DNA methylation profiles in diabetes-related pathways. Thus far, no epidemiologic studies have evaluated early-life arsenic exposure with diabetes risk. Supplementation trials have shown B vitamins can reduce blood arsenic levels in highly exposed, undernourished populations. Animal evidence supports that adequate B vitamin status can rescue early-life arsenic-induced diabetes risk, although human data is lacking.
Experimental animal studies and human evidence on the association of in utero arsenic exposure with alterations in gene expression pathways related to diabetes in newborns, support the potential role of early-life arsenic exposure in diabetes development, possibly through increased insulin resistance. Given pervasive arsenic exposure and the challenges to eliminate arsenic from the environment, research is needed to evaluate prevention interventions, including the possibility of low-cost, low-risk nutritional interventions that can modify arsenic-related disease risk.
KeywordsArsenic Diabetes Early-life exposures Nutrition One-carbon metabolism
Ana Navas-Acien reports support from the National Institute of Environmental Health Sciences (P42ES010349, P30ES009089, R01ES028758, R01ES025216).
Miranda J. Spratlen reports support from the National Institutes of Health (F31ES027796).
Ahlam Abuawad reports support from the National Institute of General Medical Sciences (GM062454).
Nancy J. LoIacono reports support from the National Institutes of Health (P42ES010349, P30ES009089, R01ES028758).
Anne K. Bozack reports support from the National Institutes of Health (T32ES007322, F31ES029019).
Mary V. Gamble reports support from the National Institutes of Health (P42ES010349).
Compliance with Ethical Standards
Conflict of Interest
Ana Navas-Acien, Miranda J. Spratlen, Ahlam Abuawad, Nancy J. LoIacono, Anne K. Bozack, and Mary V. Gamble declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.Council USNR. Critical aspects of the EPA’s IRIS assessment of inorganic arsenic: Interim Report. In: Medicine TNAoSE, ed.: The National Acadamies Press; 2013.Google Scholar
- 10.• Grau-Perez M, Kuo CC, Gribble MO, et al. Association of low-moderate arsenic exposure and arsenic metabolism with incident diabetes and insulin resistance in the Strong Heart Family Study. Environ Health Perspect. 2017;125:127004 This epidemiologic study in children and adolescents in the USA found a possible interaction between folate and vitamin B12 and arsenic metabolism biomarkers on diabetes risk.PubMedPubMedCentralCrossRefGoogle Scholar
- 14.Rojas D, Rager JE, Smeester L, et al. Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015;143:97–106.PubMedCrossRefPubMedCentralGoogle Scholar
- 17.Davila-Esqueda ME, Morales JM, Jimenez-Capdeville ME, et al. Low-level subchronic arsenic exposure from prenatal developmental stages to adult life results in an impaired glucose homeostasis. Experimental and clinical endocrinology & diabetes. official journal, German Society of Endocrinology [and] German Diabetes Association. 2011;119:613–7.CrossRefGoogle Scholar
- 28.Gamble MV, Liu X, Slavkovich V, et al. Folic acid supplementation lowers blood arsenic. Am J ClinNutr. 2007;86:1202–9.Google Scholar
- 30.Fowler PA, Drake AJ, O’Shaughnessy PJ, et al. Comment on “effects of arsenite during fetal development on energy metabolism and susceptibility to diet-induced fatty liver diseases in male mice” and “mechanisms underlying latent disease risk associated with early-life arsenic exposure: current trends and scientific gaps”. Environ Health Perspect. 2016;124:A99.PubMedPubMedCentralCrossRefGoogle Scholar
- 36.Young JL, Cai L, States JC. Impact of prenatal arsenic exposure on chronic adult diseases. Syst Biol Reprod Med. 2018:1–15.Google Scholar
- 53.• Spratlen MJ, Gamble MV, Grau-Perez M, et al. Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: evidence from the Strong Heart Study. Food Chem Toxicol. 2017;105:387–97 This epidemiologic study in a population exposed to low moderate arsenic levels support that one-carbon metabolism nutrients are related to arsenic metabolism, consistent with clinical trials of folate and B vitamin supplementation conducted in Bangladesh.PubMedPubMedCentralCrossRefGoogle Scholar
- 59.•• Huang MC, Douillet C, Dover EN, et al. Metabolic phenotype of wild-type and As3mt-knockout C57BL/6J mice exposed to inorganic arsenic: the role of dietary fat and Folate intake. Environ Health Perspect. 2018;126:127003 This experimental study in mice showed that joint exposure to arsenite and folate could rescue the metabolic effects induced by arsenite in male mice but not in female.PubMedPubMedCentralCrossRefGoogle Scholar
- 76.Hsueh YM, Chiou HY, Huang YL, et al. Serum beta-carotene level, arsenic methylation capability, and incidence of skin cancer. Cancer Epidemiol Biomark Prev. 1997;6:589–96.Google Scholar