Gestational Diabetes Mellitus and Developmental Programming

Abstract

During normal pregnancy, increased insulin resistance acts as an adaptation to enhance materno-foetal nutrient transfer and meet the nutritional needs of the developing foetus, particularly in relation to glucose requirements. However, about 1 in 6 pregnancies worldwide is affected by the inability of the mother’s metabolism to maintain normoglycaemia, with the combination of insulin resistance and insufficient insulin secretion resulting in gestational diabetes mellitus (GDM). A growing body of epidemiologic work demonstrates long-term implications for adverse offspring health resulting from exposure to GDM in utero. The effect of GDM on offspring obesity and cardiometabolic health may be partly influenced by maternal obesity; this suggests that improving glucose and weight control during early pregnancy, or better still before conception, has the potential to lessen the risk to the offspring. The consequences of GDM for microbiome modification in the offspring and the impact upon offspring immune dysregulation are actively developing research areas. Some studies have suggested that GDM impacts offspring neurodevelopmental and cognitive outcomes; confirmatory studies will need to separate the effect of GDM exposure from the complex interplay of social and environmental factors. Animal and human studies have demonstrated the role of epigenetic modifications in underpinning the predisposition to adverse health in offspring exposed to suboptimal hyperglycaemic in utero environment. To date, several epigenome-wide association studies in human have extended our knowledge on linking maternal diabetes-related DNA methylation marks with childhood adiposity-related outcomes. Identification of such epigenetic marks can help guide future research to develop candidate diagnostic biomarkers and preventive or therapeutic strategies. Longer-term interventions and longitudinal studies will be needed to better understand the causality, underlying mechanisms, or impact of GDM treatments to optimize the health of future generations.

Environmental Nanoparticles Reach Human Fetal Brains

“…NP (used here interchangeably with UFPM) size, shape, charge, surface composition, coating with biocompatible molecules, corona formation, and, certainly, stage of embryonic/fetus/placental maturation are key factors impacting free radical oxidative stress, inflammation, restricted placental growth, and the activation of placental toll-like receptors (TLRs), to name a few [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. There is a deep concern regarding uterine environmental exposures, the developmental origins of disease, and the fetal programming model predicting lifelong consequences from early intrauterine and/or postnatal exposures to insults significant in length, cumulative doses, and properties favoring specific cell damage [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Experimentally, NPs cause fetal developmental toxicity, and the early stages of brain organogenesis are highly vulnerable to reactive oxygen species (ROS); ultrastructural alterations in mitochondria, endoplasmic reticulum (ER), and Golgi complexes; downregulation of neuronal glutamate transporters; and, ultimately, the impairment of cognition and alterations in animal behavior [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Polish Women Have Moderate Knowledge of Gestational Diabetes Mellitus and Breastfeeding Benefits

“…Assuming, on the basis of data from previous years, that about 3.6% of pregnant women develop gestational diabetes mellitus, this means that last year almost 13,000 women will have suffered from glucose imbalance [ 55 ]. The epigenetic changes related to glycemic imbalance (gestational programming) affect the health of the offspring [ 33 , 56 , 57 , 58 ]. The modified environment in utero of obese and diabetic mothers has an impact on the programming of fetal metabolic functions [ 33 , 58 ] and, eventually, on the health of the next generation.…”

“…The epigenetic changes related to glycemic imbalance (gestational programming) affect the health of the offspring [ 33 , 56 , 57 , 58 ]. The modified environment in utero of obese and diabetic mothers has an impact on the programming of fetal metabolic functions [ 33 , 58 ] and, eventually, on the health of the next generation. A clear understanding of the impact of GDM and its short- and long-term consequences for mothers and children by the government and public institutions will significantly contribute to controlling and slowing the progression of the diabetes epidemic [ 33 , 58 ].…”

“…The modified environment in utero of obese and diabetic mothers has an impact on the programming of fetal metabolic functions [ 33 , 58 ] and, eventually, on the health of the next generation. A clear understanding of the impact of GDM and its short- and long-term consequences for mothers and children by the government and public institutions will significantly contribute to controlling and slowing the progression of the diabetes epidemic [ 33 , 58 ]. Furthermore, it is imperative to strengthen the national strategy to support and promote breastfeeding.…”

Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

“…Epigenomic changes in offspring induced by maternal diabetes have been the focus of multiple research projects ( Table 2 ) and are discussed in various review articles [ 22 , 55 , 56 , 57 , 58 , 59 ]. Therefore, only major findings from selected studies will be discussed here.…”