Fuel-mediated functional teratogenesis' in offspring of diabetic mothers: Role of the neonatal period

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The kind and amount of nutrition during the critical neonatal period has a profound impact on later risk of overweight and diabetes. Offspring of diabetic mothers (ODM) are an important at-risk population showing increased prevalences of overweight and impaired glucose tolerance (IGT) already in childhood. Until recently, this was exclusively attributed to prenatal, parental and socioeconomic factors but these are not sufficient to completely explain the increased risk in ODM. We have obtained first data indicating that early neonatal ingestion (1st week of life) of breast milk from diabetic mothers might be a new, as yet unknown risk factor for lasting malprogramming of overweight disposition in ODM. Against the background of these first results, however, a number of important questions remain to be answered. First, the magnitude of the effect of early neonatal ingestion of `diabetic¿ breast milk, especially as compared to the impact of maternal glycemia during pregnancy, is unknown. Second, it is unclear whether rapid neonatal weight gain might occasionally mediate the effects of neonatal breast feeding. Third, we do not know whether early neonatal ingestion of `diabetic¿ breast milk might also affect long-term outcome at higher offspring age. Fourth, pathogenetic factors in early `diabetic¿ breast milk possibly responsible for these effects are completely unknown. To gain answers to these questions, we propose a two-part study which will endure two years and needs to be supported by two doctoral fellowships and a technical assistant. In part A, we will create and analyze a completed database of the prospective `Kaulsdorf Cohort Study (KCS)¿ to identify a possible type-specific (gestational diabetes vs. type 1 diabetes during pregnancy) and/or dose-response relationship between neonatal ingestion of `diabetic¿ colostrum, neonatal weight gain, and subsequent risk of overweight and/or IGT in ODM, and compare it to the impact of the degree of maternal hyperglycemia during the 1st, 2nd and/or 3rd trimester of pregnancy, and this under consideration of a large range of prenatal, parental and socioeconomic confounders. In part B, we will, moreover, focus on potential pathogenetic factors by conducting a clinical investigation, the `Diabetic Colostrum Study (DCS)¿ in ODM (gestational diabetes vs. type 1 diabetes) and offspring of non-diabetic women to compare the composition and discover possible alterations of early `diabetic¿ breast milk as well as its possible dose-response relationship to neonatal weight gain, an important risk factor and mediator for lasting adipogenic and diabetogenic outcome. In summary, the proposed study is expected to provide an important contribution to the knowledge on whether and how alterations in early `diabetic¿ breast milk may represent a risk factor for later overweight and/or IGT and diabetes in ODM. Ultimately, the anticipated data should help to identify new strategies to primarily prevent overweight and diabetes in this permanently increasing at-risk population.