Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies

Abstract

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

“…In GDM, the stress is enhanced due to hyperglycemia, which disturbs the electron transport chain in the mitochondria, leading to enhanced production of superoxide anion radicals [ 182 ]. Oxidative stress in GDM could also be amplified by the activation of the following pathways: protein kinase C (PKC), polyol, hexosamine, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [ 182 , 183 ]. Moreover, oxidative stress contributes to insulin resistance by activating JNK and NF-κB [ 175 ].…”

“…In response to hyperglycemia, the glycolysis pathway that is responsible for the breakdown of glucose is upregulated. As a result, when fructose 1:6-bisphosphate (a component of glycolysis pathway) breaks down into glyceraldehyde-3-phosphate (G3P), accumulated levels of G3P elevate the production of diacylglycerol (DAG), which in turn, activates PKC that stimulates NADPH oxidase and results in increased ROS [ 182 , 183 ].…”

“…NADPH thus becomes deficient, and consequently, so does glutathione (GHS). Reduction of GHS production indicates the promotion of ROS [ 182 , 183 ].…”

“…The PPP is parallel to glycolysis and generates NADPH [ 184 ]. In other words, in a hyperglycemic environment, the hexosamine pathway is activated, resulting in suppression of G6PD, which consequently reduces NADPH, and hence, GHS, which increases ROS and oxidative stress [ 182 , 183 ].…”

“…NADPH oxidase is a group of enzymes that work toward generating hydrogen peroxide (H 2 O 2 ) and superoxide (O − 2 ) via the transfer of electrons from NADPH to molecular oxygen. In the hyperglycemic state, NADPH oxidase is activated and oxidative stress occurs as a result [ 182 , 183 ].…”