title: Arsenic exposure is associated with diminished insulin sensitivity in non-diabetic Amish adults.
abstract: Substantial evidence supports an association between diabetes and arsenic at high exposure levels, but results are mixed at low exposure levels. The aetiology of diabetes involves insulin resistance and β-cell dysfunction. However, only a few epidemiologic studies have examined measures of insulin resistance and β-cell function in relation to arsenic exposure, and no studies have tested for associations with the oral glucose tolerance test (OGTT). We examined the association between urinary total arsenic and OGTT-based markers of insulin sensitivity and β-cell function.
  
  
  
  We studied 221 non-diabetic adults (mean age = 52.5 years) from the Amish Family Diabetes Study. We computed OGTT-based validated measures of insulin sensitivity and β-cell function. Generalized estimating equations accounting for sibship were used to estimate associations.
  
  
  
  After adjusting for age, sex, waist-to-hip ratio and urinary creatinine, an interquartile range increase in urinary total arsenic (6.24 µg/L) was significantly, inversely associated with two insulin sensitivity measures (Stumvoll metabolic clearance rate = -0.23 mg/(kg min), (95% CI: -0.38, -0.089), p = 0.0015; Stumvoll insulin sensitivity index = -0.0029 µmol/(kg min pM), (95% CI: -0.0047, -0.0011), p = 0.0015). Urinary total arsenic was also significantly associated with higher fasting glucose levels (0.57 mg/dL (95% CI: 0.06, 1.09) per interquartile range increase, p = 0.029). No significant associations were found between urinary total arsenic and β-cell function measures.
  
  
  
  This preliminary study found that urinary total arsenic was associated with insulin sensitivity but not β-cell function measures, suggesting that low-level arsenic exposure may influence diabetes risk through impairing insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.|Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sung Kyun
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.affiliation: Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Kristi D
authors.initials: KD
authors.lastname: Silver
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.affiliation: Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Veterans Affairs and Veterans Affairs Medical Center Baltimore Geriatric Research Education and Clinical Center (GRECC), Baltimore, MD, USA.
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D061365:Amish / Q000706:statistics & numerical data; D001151:Arsenic / Q000009:adverse effects* / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D003920:Diabetes Mellitus / Q000139:chemically induced*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001151:Arsenic
keywords: arsenic; insulin sensitivity; oral glucose tolerance test; β-cell function