title: Multivariate path analysis of serum 25-hydroxyvitamin D concentration, inflammation, and risk of type 2 diabetes mellitus.
abstract: OBJECTIVE
  Despite growing interest in the protective role that vitamin D may have in health outcomes, little research has examined the mechanisms underlying this role. This study aimed to test two hypotheses: (1) serum 25-hydroxyvitamin D [25(OH)D] is inversely associated with type 2 diabetes mellitus (T2DM) and elevated hemoglobin A1c; (2) these associations are mediated by serum C-reactive protein (CRP).
  
  
  METHODS
  Participants aged 20 and older in 2001-2006 National Health and Nutrition Examination Surveys (n = 8,655) with measures of serum 25(OH)D, CRP, hemoglobin A1c, and other important covariates were included in the present study. Logistic regression and path analysis methods were applied to test the study hypotheses.
  
  
  RESULTS
  Decreased serum 25(OH)D concentration was significantly associated with increased odds of T2DM. In males, an estimated 14.9% of the association between 25(OH)D and hemoglobin A1c was mediated by serum CRP. However, this mediation effect was not observed in females.
  
  
  CONCLUSIONS
  Using a nationally representative sample, the present study extends previous research and provides new evidence that the effect of decreased serum vitamin D concentration on T2DM may proceed through increased systemic inflammation in males. Longitudinal studies and randomized control trials are needed to confirm the present findings.
authors.affiliation: Department of Epidemiology and Biostatistics, Drexel University School of Public Health, 1505 Race Street, Bellet Building 6th Floor, Philadelphia, PA 19102, USA.
authors.forename: Shaum M
authors.initials: SM
authors.lastname: Kabadi
authors.forename: Longjian
authors.initials: L
authors.lastname: Liu
authors.forename: Amy H
authors.initials: AH
authors.lastname: Auchincloss
authors.forename: Issa F
authors.initials: IF
authors.lastname: Zakeri
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D004198:Disease Susceptibility; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012737:Sex Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D006442:Glycated Hemoglobin; D014807:Vitamin D; C517652:hemoglobin A1c protein, human; C104450:25-hydroxyvitamin D