title: Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women.
abstract: OBJECTIVE
  The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk.
  
  
  METHODS
  We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis.
  
  
  RESULTS
  LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.)
  
  
  CONCLUSIONS
  LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Hevener
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
authors.forename: Lihong
authors.initials: L
authors.lastname: Qi
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.forename: Rasa
authors.initials: R
authors.lastname: Kazlauskaite
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brennan
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001724:Birth Weight; D001794:Blood Pressure; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology*; D019040:E-Selectin / Q000097:blood; D005006:Ethnicity; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D017698:Postmenopause; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019040:E-Selectin