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Low birth weight, mediating biomarkers predicted type 2 diabetes
Low birth weight could predict increased type 2 diabetes risk later in life, with insulin resistance appearing to be the main mediator, according to research published in Diabetologia.
Circulating levels of sex hormone-binding globulin (SHBG), E-selectin and systolic blood pressure further explain the effect, according to researchers.
“In this largest prospective cohort study of women in the United States, low birth weight was directly associated with the development of diabetes later in life,” Simin Liu, MD, ScD, of the Alpert Medical School at Brown University, told Endocrine Today.
Simin Liu
“An improved understanding of the mechanisms through which low birth weight may influence type 2 diabetes risk may improve clinical risk stratification,” Liu said. “Also, an accurate assessment of the specific biomarker mediating the low birth weighttype 2 diabetes relation could be used to monitor or prevent early for those who had suffered from low birth weight.”
To investigate the relationship between low birth weight (LBW) and type 2 diabetes risk, along with the mediation effects of relevant biomarkers, Liu and colleagues from other institutions looked at health records from the Women’s Health Initiative-Observational Study.
The researchers measured baseline plasma concentrations of various type 2 diabetes biomarkers in a multiethnic cohort of 1,259 women with incident type 2 diabetes and 1,790 controls. Self-reported birth weight was recorded; low birth weight was defined at <2.72 kg.
Total effect of LBW on type 2 diabetes risk was separated into effects either mediated by a specific biomarker or not mediated by this biomarker through counterfactual model-based mediation analysis.
LBW was associated with higher type 2 diabetes risk. Women with LBW had a multivariable-adjusted OR of 2.15 (95% CI, 1.54-3) vs. those with birth weights between 3.63 and 4.54 kg.
Insulin resistance, based on HOMA-IR, mediated 47% of the total effect. Elevated E-selectin concentration accounted for 25% of the total effect, decreased SHBG concentration for 24% and increased systolic blood pressure for 8%.
The researchers noted the sum of each mediator’s contribution could exceed 100%, without an upper limit, due to interactions among the mediators.
“To lower one’s risk of developing diabetes later in life, we need to further understand what may prevent some early life events such as low birth weight, particularly concerning specific nutritional strategies that may modify processes of endothelial dysfunction, inflammation, insulin resistance and sex-hormone metabolism,” Liu said. — by Allegra Tiver
For more information:
Simin Liu, MD, ScD, can be reached at The Warren Alpert School of Medicine, Brown University Box G-S121-2, Providence, RI 02912; email: simin_liu@brown.edu.
Disclosure: This work was supported by NIH grants. The WHI program was funded by the NHL BI, NNIH and the US Department of Health and Human Services.