Multigenerational diabetes mellitus

Abstract

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, “developmental programming”, has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

Glucose uptake in trophoblasts of GDM mice is regulated by the AMPK-CLUT3 signaling pathway

“…However, maternal insulin sensitivity declines progressively in the second trimester, resulting in overt insulin resistance in the third trimester of pregnancy 5 . Hyperinsulinemia as a means of compensating for insulin resistance, through the pancreas β Cells release more insulin to cope with insulin resistance or metabolic stress 6 . Insufficient β-cell compensation for maternal insulin resistance contributes to reduced insulin secretion and impaired glucose tolerance, characteristic of GDM 7 .GDM may have an adverse effect on the health of mothers and offspring.…”

Machine Learning Approach to Metabolomic Data Predicts Type 2 Diabetes Mellitus Incidence

“…Metabolomics, the detailed analysis of small-molecule metabolites within biological systems, stands out as a potent tool for uncovering metabolic changes and disease phenotypes. By mapping the entire metabolite spectrum in biological samples, it offers a detailed view of physiological and pathological states, shedding light on the biochemical pathways implicated in diabetes [1][2][3]. The metabolome's complexity and its sensitivity to genetic and environmental factors make it an ideal candidate for exploring the mechanisms of disease onset and progression.…”