title: Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000-2011.
abstract: BACKGROUND
  Among nondiabetic individuals, higher fasting blood glucose (FBG) independently predicts diabetes risk, cardiovascular disease, and dementia. Ambient PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) is an emerging determinant of glucose dysregulation. PM2.5 effects and mechanisms are understudied among nondiabetic individuals.
  
  
  OBJECTIVE
  Our goals were to investigate whether PM2.5 is associated with an increase in FBG and to explore potential mediating roles of epigenetic gene regulation.
  
  
  METHODS
  In 551 nondiabetic participants in the Normative Aging Study, we measured FBG, and DNA methylation of four inflammatory genes (IFN-γ, IL-6, ICAM-1, and TLR-2), up to four times between 2000 and 2011 (median = 2). We estimated short- and medium-term (1-, 7-, and 28-day preceding each clinical visit) ambient PM2.5 at each participant's address using a validated hybrid land-use regression satellite-based model. We fitted covariate-adjusted regression models accounting for repeated measures.
  
  
  RESULTS
  Mean FBG was 99.8 mg/dL (SD = 10.7), 18% of the participants had impaired fasting glucose (IFG; i.e., 100-125 mg/dL FBG) at first visit. Interquartile increases in 1-, 7-, and 28-day PM2.5 were associated with 0.57 mg/dL (95% CI: 0.02, 1.11, p = 0.04), 1.02 mg/dL (95% CI: 0.41, 1.63, p = 0.001), and 0.89 mg/dL (95% CI: 0.32, 1.47, p = 0.003) higher FBG, respectively. The same PM2.5 metrics were associated with 13% (95% CI: -3%, 33%, p = 0.12), 27% (95% CI: 6%, 52%, p = 0.01) and 32% (95% CI: 10%, 58%, p = 0.003) higher odds of IFG, respectively. PM2.5 was negatively correlated with ICAM-1 methylation (p = 0.01), but not with other genes. Mediation analysis estimated that ICAM-1 methylation mediated 9% of the association of 28-day PM2.5 with FBG.
  
  
  CONCLUSIONS
  Among nondiabetics, short- and medium-term PM2.5 were associated with higher FBG. Mediation analysis indicated that part of this association was mediated by ICAM-1 promoter methylation. Citation: Peng C, Bind MA, Colicino E, Kloog I, Byun HM, Cantone L, Trevisi L, Zhong J, Brennan K, Dereix AE, Vokonas PS, Coull BA, Schwartz JD, Baccarelli AA. 2016. Particulate air pollution and fasting blood glucose in nondiabetic individuals: associations and epigenetic mediation in the Normative Aging Study, 2000-2011. Environ Health Perspect 124:1715-1721; http://dx.doi.org/10.1289/EHP183.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Marie-Abele C
authors.initials: MC
authors.lastname: Bind
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.forename: Itai
authors.initials: I
authors.lastname: Kloog
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.forename: Letizia
authors.initials: L
authors.lastname: Trevisi
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.forename: Kasey
authors.initials: K
authors.lastname: Brennan
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Dereix
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000375:Aging; D000397:Air Pollution / Q000032:analysis*; D001786:Blood Glucose; D019175:DNA Methylation; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D005215:Fasting; D006801:Humans; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis*
chemical_list: D001786:Blood Glucose; D052638:Particulate Matter