Adriëtte Oostvogels

114 Chapter 4 Second, intra-uterine mechanisms could play a role as animal studies showed that offspring of dams fed a high-fat diet during pregnancy had increased insulin levels, as well as pancreatic remodelling and change of pancreatic β -cell function. 24 Subsequently, altered insulin sensitivity is associated with dyslipidaemia, 10 which, in turn, may cause hepatic alteration with more disruption of lipid levels. 25 We found no association between maternal lipids and offspring’s glycaemic control. However, the age of our children (5-6 years) might be too young to detect effects of decreased insulin sensitivity on lipid levels. Moreover, the animal models only investigate the impact of maternal high-fat diet during pregnancy and not the impact of maternal lipid profile on changes in offspring’s metabolism. More research on which maternal substrates change as a consequence of a high-fat diet and cause these alterations in the offspring will provide more insight into the underlying mechanism. In addition, the results from animal studies cannot directly be translated to the human situation. Although we found no evidence for the programming of offspring’s lipids through glycaemic control, sex differences indicate a programming factor in the association between maternal and offspring’s lipids. Sex differences are also reported in many human and animal studies which examined a relationship between a certain intra- uterine exposure and a health aspect of the offspring. 26 There is increasing evidence that this is due to a different placental function between boys and girls, caused by differences in gene expression in response to maternal metabolic status. 27 However, the exact mechanism behind the sex differences in placental function and the response in later life remains unclear. Increased fat percentage is associated with altered lipid levels, 28 probably through increased insulin resistance. 10 It is reported that maternal lipids are associated with increased offspring’s fat percentage in childhood. 11 However, in this study, fat percentage did not mediate the association between maternal and offspring’s lipids. This might be a result of the adjustment made for pBMI, which is directly associated with both maternal lipid profile and offspring’s fat percentage, independent of maternal lipid levels. 11 Strengths and limitations This study was embedded in a large community-based cohort with a long follow-up time and a wide range of maternal and offspring’s lipid substrates. The wide range of available characteristics allowed correcting for many potential confounders and covariates to minimize bias.