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  • Title: Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study.
    Author: Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, Dabelea D.
    Journal: Diabetologia; 2015 May; 58(5):937-41. PubMed ID: 25628236.
    Abstract:
    AIMS/HYPOTHESIS: In women who are overweight or obese before or during pregnancy there is an associated risk of increased fetal growth and higher birthweight. The metabolic phenotype of the overweight/obese pregnant woman, characterised by higher than normal insulin resistance (IR) and increased circulating fuels, suggests a mechanism resulting in fetal overnutrition and subsequent increased adiposity. We tested the fuel-mediated hypothesis in an observational pre-birth cohort of 951 mother-offspring pairs, the Healthy Start study. METHODS: We conducted a path analysis to estimate the simultaneous effects of maternal IR and maternal fuels (fasting glucose, triacylglycerol [TG] and NEFA levels) in late pregnancy in mediating the relationship between maternal pre-pregnancy BMI and neonatal adiposity (per cent fat mass [%FM]). RESULTS: The total effect of maternal BMI on neonatal %FM was significant (total effect 0.16, 95% CI 0.08, 0.22, p < 0.001). The mediated path including maternal IR and glucose levels together accounted for 21% (p < 0.01) of the total effect of maternal BMI on neonatal %FM while the mediating effects of all other fuels were non-significant. CONCLUSIONS/INTERPRETATION: Using a novel application of path analysis our data implicate maternal IR and glucose levels as important mediators of the association between maternal and infant adiposity.
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