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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity / physiology*
  • Adult
  • Birth Weight / physiology
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Female
  • Humans
  • Infant, Newborn
  • Insulin Resistance / physiology*
  • Lipids / blood
  • Male
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Overweight / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism


  • Blood Glucose
  • Lipids