Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women. Its early diagnosis seems to have a significant impact on the developing fetus, the course of delivery, and the neonatal period. It may also affect the later stages of child development and subsequent complications in the mother. Therefore, the crux of the matter is to find a biopredictor capable of singling out women at risk of developing GDM as early as the very start of pregnancy. Apart from the well-known molecules with a proven and clear-cut role in the pathogenesis of GDM, e.g., adiponectin and leptin, a potential role of newer biomolecules is also emphasized. Less popular and less known factors with different mechanisms of action include: galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, fatty acid-binding protein 4 (FABP4), fibroblast growth factor 21, and lipocalin-2. The aim of this review is to present the potential and significance of these 13 less known biomolecules in the pathogenesis of GDM. It seems that high levels of FABP4, low levels of irisin, and high levels of under-carboxylated osteocalcin in the serum of pregnant women can be used as predictive markers in the diagnosis of GDM. Hopefully, future clinical trials will be able to determine which biomolecules have the most potential to predict GDM.

The WWOX/HIF1A Axis Downregulation Alters Glucose Metabolism and Predispose to Metabolic Disorders

“…For these reasons, WWOX targeting may prove to be more effective. Leptin expression, another one of adipocytokines, controlling insulin-dependent glucose transport to adipocytes [ 91 ] was found to be hypoxia-inducible [ 92 ], which is stimulated in adipose tissue [ 93 ] and placenta [ 94 ] through HIF1. Hypoxia-inducible factor is also responsible for upregulation of visfatin mRNA expression [ 95 ] in the fat tissue of obesity patients and significantly higher levels of visfatin was observed in the population of obese T2DM patients compared to healthy subjects [ 96 ].…”

New Insights into Adipokines in Gestational Diabetes Mellitus

“…ANGPTL8, a 22 kDa protein, is secreted by the liver and adipose tissue and plays important roles in glucose homeostasis, lipid metabolism and inflammation [ 50 ]. Today there is a discussion on whether ANFPTL8 is able to induce pancreatic beta-cell proliferation and increase insulin secretion, although the consensus is that it is not capable of such actions [ 10 ]. Many studies have shown that ANGPTL8 correlates negatively with HDL-C levels and positively with triglyceride levels, making it a crucial modulator of lipid metabolism [ 51 ].…”

“…Although some key pathophysiological mechanisms in GDM have been extensively described to date, it is in the last few decades that several adipokines have shown some involvement in the metabolic alterations underlying GDM. Today, there are excellent reviews of the role of adipokines in GDM, with special focus on the maternal circulating profile [ 8 , 9 , 10 , 11 ]. However, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation.…”

Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome

“…Due to placental hormones such as human placental lactogen, progesterone, cortisol, growth hormone, and prolactin, pregnancy is linked to physiological IR, especially in the second and third trimester of pregnancy [ 43 , 44 ]. Recently, the role of leptin stimulating IR and the inhibitory role of adiponectin have been emphasized [ 45 , 46 , 47 , 48 , 49 , 50 ].…”