Exploration of the shared pathophysiological mechanisms of gestational diabetes and large for gestational age offspring

Abstract

Gestational diabetes mellitus (GDM) and large for gestational age (LGA) offspring are two common pregnancy complications. Connections also exist between the two conditions, including mutual maternal risk factors for the conditions and an increased prevalence of LGA offspring amongst pregnancies affected by GDM. Thus, it is important to elucidate potential shared underlying mechanisms of both LGA and GDM. One potential mechanistic link relates to macronutrient metabolism. Indeed, derangement of carbohydrate and lipid metabolism is present in GDM, and maternal biomarkers of glucose and lipid control are associated with LGA neonates in such pregnancies. The aim of this paper is therefore to reflect on the existing nutritional guidelines for GDM in light of our understanding of the pathophysiological mechanisms of GDM and LGA offspring. Lifestyle modification is first line treatment for GDM, and while there is some promise that nutritional interventions may favourably impact outcomes, there is a lack of definitive evidence that changing the macronutrient composition of the diet reduces the incidence of either GDM or LGA offspring. The quality of the available evidence is a major issue, and rigorous trials are needed to inform evidence-based treatment guidelines.

C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients with Gestational Diabetes Mellitus: A Case-Control Study

“…The prevalence ranges from less than 2% in Sweden to 20.6% in United Arab Emirates [30]. GDM is a worldwide metabolic disorder that has negative maternal and neonatal effects with long-term consequences [31,32]. It is associated with adverse maternal health outcomes such as gestational hypertension, pre-eclampsia, caesarean section, and neonatal outcomes including hyperinsulinemia, macrosomia (usually defined as a neonate weighing over 4 kg), shoulder dystocia, and hypoglycemia.…”

The Role of Maternal Weight in the Hierarchy of Macrosomia Predictors; Overall Effect of Analysis of Three Prediction Indicators

“…In the current analysis, maternal characteristics were potential predictors identified in the literature as potential risk factors of macrosomia/LGA [ 1 , 2 , 3 , 8 , 10 , 11 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

“…What is important, in well developed countries, is that the number of macrosomic newborns was reported to have increased from 5–20% to 15–25% [ 2 , 6 ]. Macrosomia is defined as birth weight above 4000 g regardless of gestational age; a large-for-gestational age (LGA) is defined as the weight > 90th percentile for the newborn sex and its gestational age, and for the particular population [ 1 , 7 , 8 ].…”

The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neonatal birth weight

“…Among pregnant women with GDM, the pancreatic beta cells failed to compensate sufficiently 32 and gluconeogenesis was affected, resulting in a hyperglycemic metabolic environment for the mother, as the glucose shifted down the placental concentration gradient. Thus, this maternal hyperglycemia could lead to fetal hyperglycemia, 33 , 34 which in turn stimulated fetal pancreas to increase the production of insulin. Because insulin is an important fetal growth hormone, the resulting hyperinsulinemia could lead to fetal overgrowth.…”