Biomarkers of endothelial dysfunction in relation to impaired carbohydrate metabolism following pregnancy with gestational diabetes mellitus

Göbl, Christian; Bozkurt, Latife; Yarragudi, Rajashri; Prikoszovich, Thomas; Tura, Andrea; Pacini, Giovanni; Koppensteiner, Renate; Kautzky‐Willer, Alexandra

doi:10.1186/s12933-014-0138-3

Cited by 37 publications

(32 citation statements)

References 43 publications

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“…A great focus was placed on the production of IL-1β by placental cells in this study. It is primarily involved in the signaling cascade that triggers translocation of the transcription factor nuclear factor-kappa B (NFKB) into the nucleus where it induces the transcription of pro-and anti-inflammatory genes including IL-6, iNOS, and COX-2 [25]. Changes in IL-1β levels associated with the inflammatory biomarkers iNOS and MCP-1, as we found, suggest that lower mean blood glucose activates the expression of the inflammatory cascade at both plasma and placenta levels.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia induces inflammatory mediators in the human chorionic villous

et al. 2018

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This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia induces inflammatory mediators in the human chorionic villous

et al. 2018

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“…And Bo et al [ 28 ] showed women with previous GDM have been shown to express early markers of vascular dysfunction such as increased intima-media thickness of carotid arteries(C-IMT). Zajdenverg et al [ 29 ] showed microcirculation abnormality, evaluated by papillae rectification, was carried in young non-diabetic women with pGDM. Our study showed the normoglycemic women with pGDM were presented with elevated glycemic variability parameters, when compared with the women without pGDM.…”

Section: Discussionmentioning

confidence: 99%

“…Our presented study demonstrated that glycemic variability parameters SDBG, MBG, MODD, MAGE and AUC pp in pGDM group were higher than in the control group. Women with pGDM carried with early markers of vascular dysfunction [ 28 , 29 ]. Hence, it implies that glycemic variability may be related to early markers of vascular dysfunction in women with pGDM.…”

Section: Discussionmentioning

confidence: 99%

Glycemic variability in normal glucose tolerance women with the previous gestational diabetes mellitus

Wang

Zhao

et al. 2015

Diabetol Metab Syndr

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BackgroundWomen with previous gestational diabetes mellitus (pGDM) and postpartum normal glucose tolerance (NGT) may carry impaired islet β cell secretion, insulin resistance and subsequent altered glucose homeostasis. And certain normoglycemic groups at risks of diabetes were presented with elevated glycemic variability. The aim of study was to investigate the glycemic variability in NGT women with pGDM.MethodsTotal 48 NGT women with pGDM (pGDM group) and 48 age- and BMI-matched NGT women without pGDM (control group) were recruited in the study. Integrated β cell function was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from oral glucose tolerance test. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 h. The multiple parameters of glycemic variability included the mean blood glucose (MBG), standard deviation of blood glucose (SDBG), mean of daily differences (MODD), mean amplitude of glycemic excursions (MAGE) and the incremental areas above preprandial glucose values (AUCpp).ResultsThe pGDM group had a higher MBG (6.5 ± 0.9 vs. 5.9 ± 0.8 mmol/L, p < 0.05), SDBG (1.3 ± 0.3 vs. 0.9 ± 0.2 mmol/L, p < 0.05), MODD (1.4 ± 0.3 vs. 1.1 ± 0.2 mmol/L, p < 0.05), MAGE (2.7 ± 0.4 vs. 1.8 ± 0.5 mmol/L, p < 0.05), and AUCpp (26.8 ± 3.4 vs. 19.2 ± 3.2 mmol/L·h, p < 0.05), when compared to the control group, and the differences remained significant after adjusting for anthropometric indices and metabolic risk factors. Islet β cell function index ISSI-2 in the pGDM group was lower than in the control group (p < 0.05). MBG, SDBG, MODD, MAGE and AUCpp were all negatively associated with ISSI-2 in the pGDM group (r = −0.31, −0.30, −0.34, −0.48 and −0.54, respectively, p < 0.05), and the correlations remained significant after adjusting for anthropometric indices and metabolic risk factors.ConclusionsNormal glucose tolerance women with pGDM were presented with elevated glycemic variability, which may be associated with impaired islet β cell function.

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“…Despite this, abnormal uterine blood flow has not been evidenced to affect glucose transfer to the fetus (Palacín et al 1985). Instead, endothelial dysfunction during GDM pregnancy may be associated with impaired cardiometabolism postpartum (Göbl et al 2014). The GDM placenta exhibits significant increases in key markers of endothelial dysfunction, such as endothelial-derived reactive oxygen and nitrative-derived species (Casanello et al 2007, Westermeier et al 2009.…”

Section: Endothelial Cell Dysfunctionmentioning

confidence: 99%

Molecular pathways disrupted by gestational diabetes mellitus

Nguyen-Ngo

Jayabalan

Salomón

et al. 2019

Journal of Molecular Endocrinology

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Gestational diabetes mellitus (GDM) imposes serious short- and long-term health problems for mother and baby. An effective therapeutic that can reduce the incidence of GDM and improve long-term maternal and fetal outcomes is a major research priority, crucially important for public health. A lack of knowledge about the underlying pathophysiology of GDM has hampered the development of such therapeutics. What we do know, however, is that maternal insulin resistance, low-grade inflammation and endothelial cell dysfunction are three central features of pregnancies complicated by GDM. Indeed, data generated over the past decade have implicated a number of candidate regulators of insulin resistance, inflammation and endothelial cell dysfunction in placenta, maternal adipose tissue and skeletal muscle. These include nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptors (PPARs), sirtuins (SIRTs), 5′ AMP-activated protein kinase (AMPK), glycogen synthase kinase 3 (GSK3), PI3K/mTOR, inflammasome and endoplasmic reticulum (ER) stress. In this review, the identification of these as key modulators of GDM will be discussed. The biochemical pathways involved in the formation of these may represent potential sites for intervention that may translate to therapeutic interventions to prevent the development of GDM.

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Biomarkers of endothelial dysfunction in relation to impaired carbohydrate metabolism following pregnancy with gestational diabetes mellitus

Cited by 37 publications

References 43 publications

Hyperglycemia induces inflammatory mediators in the human chorionic villous

Hyperglycemia induces inflammatory mediators in the human chorionic villous

Glycemic variability in normal glucose tolerance women with the previous gestational diabetes mellitus

Molecular pathways disrupted by gestational diabetes mellitus

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