Song Yan, Huang Yen-Tsung, Song Yiqing, Hevener Andrea L, Ryckman Kelli K, Qi Lihong, LeBlanc Erin S, Kazlauskaite Rasa, Brennan Kathleen M, Liu Simin
Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
Diabetologia. 2015 Jun;58(6):1220-30. doi: 10.1007/s00125-014-3479-2. Epub 2015 Jan 8.
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.
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.
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.
目的/假设：本研究旨在探讨低出生体重（LBW）与日后2型糖尿病风险之间的前瞻性关系，以及2型糖尿病生物标志物在LBW与2型糖尿病风险之间的中介作用。
在女性健康倡议观察性研究中，我们测量了1259例2型糖尿病新发病例和1790例对照者的多种2型糖尿病生物标志物的基线血浆浓度。记录参与者的自我报告出生体重。使用基于反事实模型的中介分析，将LBW对2型糖尿病风险的总体效应分为由特定生物标志物介导的效应和不由该生物标志物介导的效应。
LBW与2型糖尿病风险增加显著相关。与出生体重在3.63 - 4.54千克的女性相比，LBW（<2.72千克）的女性多变量调整后的OR为2.15（95%CI，1.54，3.00）。胰岛素抵抗（以HOMA-IR表示）介导了总体效应的47%。性激素结合球蛋白（SHBG）浓度降低占总体效应的24%，E-选择素浓度升高占25%，收缩压升高占LBW对2型糖尿病风险总体效应的8%。（由于不同中介因素之间的相互作用，每个个体中介因素的贡献总和可能超过100%，且无上限。）
结论/解读：LBW可直接预测日后患2型糖尿病的较高风险。LBW对2型糖尿病风险的影响似乎主要由胰岛素抵抗介导，而胰岛素抵抗又进一步由SHBG、E-选择素的循环水平和收缩压来解释。该研究为2型糖尿病发病风险较高的人群提供了潜在的风险分层。
