title: Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.
abstract: Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study.
  
  
  
  A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥ 126 mg/dL, 2-h glucose ≥ 200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications.
  
  
  
  Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations.
  
  
  
  Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan chinchik@gmail.com.
authors.forename: Chin-Chi
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: MedStar Health Research Institute, Hyattsville, MD Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: MedStar Health Research Institute, Hyattsville, MD Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.affiliation: University of Southern California, Los Angeles, CA.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Gribble
authors.affiliation: Missouri Breaks Industries Research, Inc., Timber Lake, SD.
authors.forename: Lyle G
authors.initials: LG
authors.lastname: Best
authors.affiliation: Institute of Chemistry - Analytical Chemistry, Karl-Franzens University Graz, Graz, Austria.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Francesconi
authors.affiliation: Institute of Chemistry - Analytical Chemistry, Karl-Franzens University Graz, Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Goessler
authors.affiliation: Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ana
authors.initials: A
authors.lastname: Navas-Acien
mesh_terms: D000368:Aged; D001130:Arizona / Q000453:epidemiology; D001151:Arsenic / Q000378:metabolism* / Q000633:toxicity* / Q000652:urine; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism* / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D007198:Indians, North American / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009658:North Dakota / Q000453:epidemiology; D009825:Oklahoma / Q000453:epidemiology; D011446:Prospective Studies; D013023:South Dakota / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D001151:Arsenic