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Diabetologia. 2015 May;58(5):937-41. doi: 10.1007/s00125-015-3505-z. Epub 2015 Jan 28.

Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study.

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Department of Epidemiology, Colorado School of Public Health, Campus Box B119, 13001 East 17th Ave, Room W3110, Aurora, CO, 80045, USA.



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.


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]).


The total effect of maternal BMI on neonatal %FM was significant (total effect 0.16, 95% CI 0.08, 0.22, pā€‰<ā€‰0.001). The mediated path including maternal IR and glucose levels together accounted for 21% (pā€‰<ā€‰0.01) of the total effect of maternal BMI on neonatal %FM while the mediating effects of all other fuels were non-significant.


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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