Association of gestational diabetes with abnormal maternal vascular endothelial function

Knock, Greg A.; McCarthy, Andrew L.; Lowy, C.; Poston, Lucilla

doi:10.1111/j.1471-0528.1997.tb11051.x

Cited by 85 publications

(65 citation statements)

References 29 publications

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“…Indeed, sICAM1 and sVCAM1 levels are higher in insulin resistance, obesity and type 2 diabetes (Guler et al 2002, Leinonen et al 2003, Kent et al 2004. There is also evidence indicating that women with GDM develop endothelial dysfunction during pregnancy (Knock et al 1997), and despite returning to NGT, endothelial dysfunction is still evident in women 1-year post GDM pregnancy (Pleiner et al 2007). Indeed, women with GDM have increased circulating sICAM1 and sVCAM1 levels (Mordwinkin et al 2013).…”

Section: Figurementioning

confidence: 99%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies, complicated by gestational diabetes mellitus (GDM). The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor kB (NFkB). The aim of this study was to determine whether levels of NOD1 and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous adipose tissues obtained from women with GDM when compared with those from women with normal glucose tolerance (NGT). In both omental and subcutaneous adipose tissues from NGTand GDM women, the NOD1 ligand g-D-glutamyl-meso-diaminopimelic acid (iE-DAP) significantly induced the expression and secretion of the pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8; COX2 (PTGS2) gene expression and subsequent prostaglandin production; the expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion molecules ICAM1 and VCAM1. There was no effect of the NOD2 ligand muramyl dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP were mediated via NFkB, as the NFkB inhibitor BAY 11-7082 significantly attenuated iE-DAP-induced expression and secretion of pro-inflammatory cytokines, COX2 gene expression and subsequent prostaglandin production, MMP9 expression and secretion and ICAM1 and VCAM1 gene expression and secretion. In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.

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Section: Figurementioning

confidence: 99%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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“…This is surprising since the disorder is characterised by insulin resistance, inability to increase output of insulin (Bowes et al, 1996), impaired glucose transport and insulin receptor autophosphorylation (Friedman et al, 1999;Yamashita et al, 2000) and vascular endothelial dysfunction (Knock et al, 1997). Abnormalities of plasma (Wijendran et al, 1999) and red cell (Wijendran et al, 2000) fatty acids have been reported in diettreated GDM women.…”

Section: Introductionmentioning

confidence: 99%

Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women

et al. 2004

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Objective: The polyunsaturated fatty acids, arachidonic (AA) and docosahexaenoic (DHA), are vital structural and functional components of the neural, vascular and visual systems. There is increased demand for these fatty acids during pregnancy. Diabetes impairs the synthesis of both AA and DHA. We have investigated the possibility that pregnancy-induced diabetes compromises the levels of plasma AA and DHA in newly diagnosed expectant mothers. Design: Cross-sectional study. Setting: London, UK. Subjects and methods: Venous blood was obtained from 44 women with gestational diabetes mellitus (GDM) and from the same number of nondiabetics, during the third trimester. Fatty acid composition of plasma choline phosphoglycerides (CPG), triglycerides (TG) and cholesterol esters (CE) was analysed. Results: The GDM women had higher levels of AA (20:4n-6; Po0.0001) and AA/linoleic acid ratio (20:4n-6/18:2n-6; Po0.01) in the CPG, and linoleic acid (LA; Po0.0001), total n-6 (Po0.01), DHA (Po0.05) and n-3 metabolites (Po0.05) in TG compared to their nondiabetic counterparts. Similarly, AA (Po0.0001), osbond acid (22:5n-6; Po0.05), total n-6 metabolites (Po0.0001), AA/LA (Po0.0001) and n-6 metabolites/LA (Po0.01) were higher in the CE of the GDM women. There was no difference in the levels of DHA in CPG and CE between the two groups (P40.05). Conclusions:The results of this study do not provide evidence that the activity of delta-6 or delta-5 desaturases, which are vital for the synthesis of AA and DHA, is compromised by pregnancy-induced diabetes. However, since the samples were taken at diagnosis, it is conceivable that the duration of the diabetes was too short to have a discernable adverse effect on the levels of AA and DHA in plasma lipids.

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“…Knock et al (13) reported impaired endothelial response to acetylcholine in small artery rings of pregnant women with gestational diabetes. Other authors found defective endothelium-dependent vasodilatation in euglycemic women with previous GDM (7).…”

Section: Conclusion -mentioning

confidence: 99%

Abnormal Carbohydrate Metabolism During Pregnancy

et al. 2002

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OBJECTIVE -To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS -Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endotheliumindependent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. Highresolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured.RESULTS -FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 Ϯ 1.1% in the IGT group and 4.1 Ϯ 0.9% in the GDM group vs. 10.9 Ϯ 1.1% in control subjects, P Ͻ 0.04 and P Ͻ 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P Ͻ 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r ϭ -0.60, P Ͻ 0.0001).CONCLUSIONS -Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women. Diabetes Care 25:560 -564, 2002A bnormal carbohydrate metabolism during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes (GDM), is a relatively frequent disease affecting ϳ2-5% of all pregnancies (1). In common with other maternal disorders associated with macrovascular dysfunction, abnormal carbohydrate metabolism is associated with augmented maternal and fetal-neonatal morbidity (1,2). It has been shown that women with GDM have an increased incidence of preeclampsia (3). Furthermore, these patients are more prone to development of type 2 diabetes, a known condition that leads to an increased risk for cardiovascular disease (1), later in life. Recently, several lines of evidence seem to indicate that vascular endothelial dysfunction has a role in the etiopathogenesis of vascular abnormality associated with preeclampsia and with type 2 diabetes (4 -6). In addition, impaired endothelium-dependent vasodilation has been shown in euglycemic women with a history of GDM, thus supporting the assumption that glucose metabolism derangement is closely related to vascular dysfunction (7). On the basis of these findings, it could be argued that impaired endothelial function may be a factor occurring in pregnant women with abnormal carbohydrate metabolism. To verify this hypothesis, we evaluated endothelial function, along with carbohydrate and lipid metabolism, in women with impaired gluco...

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Association of gestational diabetes with abnormal maternal vascular endothelial function

Cited by 85 publications

References 29 publications

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women

Abnormal Carbohydrate Metabolism During Pregnancy

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