title: A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus.
abstract: BACKGROUND
  Consumption of drinking water with high levels of inorganic arsenic (over 500 μg/L) has been associated with type II diabetes mellitus (DM), but previous studies have been inconclusive about risks at lower levels (<100 μg/L). We present a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of DM.
  
  
  METHODS
  This case-cohort study included 141 cases of DM diagnosed between 1984 and 1998 as part of the prospective San Luis Valley Diabetes Study. A comparison sub-cohort of 488 participants was randomly sampled from 936 eligible participants who were disease free at baseline. Individual lifetime arsenic exposure estimates were determined using a methodology that incorporates the use of a structured interview to determine lifetime residence and employment history, geospatial modeling of arsenic concentrations in drinking water, and urine arsenic concentrations. A Cox proportional hazards model with known DM risk factors as time-dependent covariates was used to assess the association between lifetime exposure to inorganic arsenic in drinking water and incident DM.
  
  
  RESULTS
  Our findings show a significant association between inorganic arsenic exposure and DM risk (hazard ratio [HR]=1.27, 95%=1.01, 1.59 per 15 μg/L) while adjusting for ethnicity and time varying covariates age, body mass index and physical activity level.
  
  
  CONCLUSIONS
  Exposure to low-level inorganic arsenic in drinking water is associated with increased risk for type II DM in this population based on a comprehensive lifetime exposure assessment.
authors.affiliation: University of Colorado, Denver, Aurora, CO 80045, United States. Kathy.James@ucdenver.edu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: James
authors.forename: Julie A
authors.initials: JA
authors.lastname: Marshall
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Jaymie R
authors.initials: JR
authors.lastname: Meliker
authors.forename: Gary O
authors.initials: GO
authors.lastname: Zerbe
authors.forename: Tim E
authors.initials: TE
authors.lastname: Byers
mesh_terms: D000328:Adult; D000368:Aged; D001151:Arsenic / Q000008:administration & dosage* / Q000009:adverse effects; D003120:Colorado / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology; D060766:Drinking Water; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014874:Water Pollutants, Chemical / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D001151:Arsenic