| Arsenic Exposure and Type 2 Diabetes:
A Systematic Review of the Experimental
and Epidemiological Evidence Ana Navas-Acien,1-4 Ellen K. Silbergeld,4 Robin A.
Streeter,1,3 Jeanne M. Clark,1,2,5 Thomas A. Burke,3,6 and
Eliseo Guallar1-3 1Department of Epidemiology, Johns Hopkins University Bloomberg
School of Public Health, 2Welch Center for Prevention, Epidemiology
and Clinical Research, Johns Hopkins Medical Institutions, 3Johns
Hopkins Center for Excellence in Environmental Public Health Tracking, Johns
Hopkins University Bloomberg School of Public Health, 4Department
of Environmental Health Sciences, Johns Hopkins University Bloomberg School
of Public Health, 5Department of Medicine, Johns Hopkins School
of Medicine, and 6Department of Health Policy and Management, Johns
Hopkins University Bloomberg School of Public Health, Baltimore, Maryland,
USA Abstract
Chronic arsenic exposure has been suggested to contribute to diabetes development. We performed a systematic review of the experimental and epidemiologic evidence on the association of arsenic and type 2 diabetes. We identified 19 in vitro studies of arsenic and glucose metabolism. Five studies reported that arsenic interfered with transcription factors involved in insulin-related gene expression: upstream factor 1 in pancreatic β-cells and peroxisome proliferative-activated receptor  in preadipocytes. Other in vitro studies assessed the effect of arsenic on glucose uptake, typically using very high concentrations of arsenite or arsenate. These studies provide limited insight on potential mechanisms. We identified 10 in vivo studies in animals. These studies showed inconsistent effects of arsenic on glucose metabolism. Finally, we identified 19 epidemiologic studies (6 in high-arsenic areas in Taiwan and Bangladesh, 9 in occupational populations, and 4 in other populations) . In studies from Taiwan and Bangladesh, the pooled relative risk estimate for diabetes comparing extreme arsenic exposure categories was 2.52 (95% confidence interval, 1.69-3.75) , although methodologic problems limit the interpretation of the association. The evidence from occupational studies and from general populations other than Taiwan or Bangladesh was inconsistent. In summary, the current available evidence is inadequate to establish a causal role of arsenic in diabetes. Because arsenic exposure is widespread and diabetes prevalence is reaching epidemic proportions, experimental studies using arsenic concentrations relevant to human exposure and prospective epidemiologic studies measuring arsenic biomarkers and appropriately assessing diabetes should be a research priority. Key words: arsenic, diabetes, glucose metabolism, meta-analysis, systematic review. Environ Health Perspect 114: 641-648 (2006) . doi:10.1289/ehp.8551 available via http://dx.doi.org/ [Online 15 December 2005]
Address correspondence to A. Navas Acien, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St., Office W7033B, Baltimore, MD 21205-2223 USA. Telephone: (410) 502-4267. Fax: (410) 955-0476. E-mail: anavas@jhsph.edu This work was supported by National Institute of Environmental Health Sciences grant 1R01 ES012673-01. A.N.-A., R.A.S., T.A.B., and E.G. were supported by the Johns Hopkins Center of Excellence in Environmental Public Health Tracking (Centers for Disease Control and Prevention grant U50CCU322417) . The authors declare they have no competing financial interests. Received 1 August 2005 ; accepted 15 December 2005. The full version of this article is available for free in HTML or PDF formats. |
