Maternal β-Cell Adaptations in Pregnancy and Placental Signalling: Implications for Gestational Diabetes

Abstract

Rates of gestational diabetes mellitus (GDM) are on the rise worldwide, and the number of pregnancies impacted by GDM and resulting complications are also increasing. Pregnancy is a period of unique metabolic plasticity, during which mild insulin resistance is a physiological adaptation to prioritize fetal growth. To compensate for this, the pancreatic β-cell utilizes a variety of adaptive mechanisms, including increasing mass, number and insulin-secretory capacity to maintain glucose homeostasis. When insufficient insulin production does not overcome insulin resistance, hyperglycemia can occur. Changes in the maternal system that occur in GDM such as lipotoxicity, inflammation and oxidative stress, as well as impairments in adipokine and placental signalling, are associated with impaired β-cell adaptation. Understanding these pathways, as well as mechanisms of β-cell dysfunction in pregnancy, can identify novel therapeutic targets beyond diet and lifestyle interventions, insulin and antihyperglycemic agents currently used for treating GDM.

Intuitive eating is associated with improved health indicators at 1-year postpartum in women with gestational diabetes mellitus

“…This is partly attributed to the subtle changes in appetite regulatory mechanisms associated with weight gain and weight retention (Ciampolini et al, 2010;Perry and Wang, 2012). Alterations in leptin (a hormone released from fat cells in adipose tissue altering food intake and control energy expenditure over the long term) signaling also act to increase the risk of diabetes in these women (Moyce and Dolinsky, 2018;Oh et al, 2018). It is therefore of utmost importance to decrease weight retention and to improve glucose control in order to reduce diabetes risk in this population.…”

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

“…Pregnancy is a period of metabolic plasticity with transient mild insulin resistance as a physiological adaptation to ensure the preferential use of the circulating glucose by the fetus, to prioritize, in this way, fetal growth [1]. During normal pregnancies, maternal sensitivity to insulin is decreased by approximately 50%, which is counteracted by an increase of approximately 250% in maternal insulin production to maintain the euglycemia [2,3].…”

The effects ofn-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus: a randomised, double-blind, placebo-controlled trial

“…GDM is associated with changes, including increased insulin resistance, dyslipidaemia, oxidative stress and inflammatory state (3) . We observed a significant improvement in PPAR-γ and LDLR mRNA expression as well as parameters of glycaemic control, TAG, VLDL-cholesterol, total cholesterol and total cholesterol:HDL-cholesterol ratio.…”

“…Based on the previous data, an increased risk of adverse perinatal consequences and a wide range of unfavourable long-term outcomes for mother and child are attributed to this condition (2) . Strong evidence suggests a link between peripheral insulin resistance, changes of inflammatory cytokines and biomarkers of oxidative stress in the pathogenesis of GDM (3) . Previous studies also suggested that both pre-existing maternal obesity and gestational diabetes are associated with decreased expression of transcription factors involved in carbohydrate and lipid metabolism such as PPAR, sterol regulatory element-binding protein 1c and increased gene expression levels of adipokines, TNF-α, IL-1β and leptin in adipose tissue (4) .…”