Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women

Yan Song, Yen Tsung Huang, Yiqing Song, Andrea L. Hevener, Kelli K. Ryckman, Lihong Qi, Erin S. LeBlanc, Rasa Kazlauskaite, Kathleen M. Brennan, Simin Liu

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Aims/hypothesis: 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/interpretation: 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.

Original languageEnglish (US)
Pages (from-to)1220-1230
Number of pages11
JournalDiabetologia
Volume58
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • Blood pressure
  • Endothelial dysfunction
  • Inflammation
  • Insulin resistance
  • Low birthweight
  • Mediation analysis
  • Sex hormone
  • Sex hormone-binding globulin
  • Telomere length
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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