scholarly journals Is there a genetic variation association in the IL-10 and TNF α promoter gene with gestational diabetes mellitus?

Hereditas ◽  
2010 ◽  
Vol 147 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Shabnam Montazeri ◽  
Sivalingam Nalliah ◽  
Ammu Kutty Radhakrishnan
Author(s):  
Xinmei Huang ◽  
Bingbing Zha ◽  
Manna Zhang ◽  
Yue Li ◽  
Yueyue Wu ◽  
...  

Abstract Objective The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Here, we investigated the potential effect of monocytes in GDM. Materials and Methods: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages and their products were measured. Results Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and closely associated with glucose level, insulin resistance and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia in both the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10 9/L. Notably, CD206 and IL-10 were significantly lower, while CD80, CD86, TNF-α and IL-6 were higher in both GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α and IL-6. Conclusions Decreased monocyte count throughout pregnancy was closely-associated with the development of GDM, macrosomia and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.


2020 ◽  
Author(s):  
Zhiwei Zhang ◽  
Hui Zhao ◽  
Aixia Wang

Background: Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM. Methods: Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, enzyme-linked immunosorbent assay (ELISA) was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA, and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight. Results: Oleuropein attenuated the elevated body weight of GDM mice, and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment. Conclusions: Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.


2020 ◽  
Vol 47 (10) ◽  
pp. 7537-7546 ◽  
Author(s):  
Wenting Xu ◽  
Mengyu Tang ◽  
Jiahui Wang ◽  
Lihong Wang

Abstract To investigate the effect of puerarin on insulin resistance and inflammation in rats with gestational diabetes mellitus (GDM). Gestational diabetic model rats were established by intraperitoneal injection of streptozotocin (25 mg/kg) combined with high-fat feeding and were randomly assigned to three groups: the control group, the GDM group, and the puerarin-treated group. Puerarin was intragastrically administered to rats daily until the offspring were born. The rats in both the GDM group and control group were administered the same volume of normal saline. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in all groups of rats were measured. Haematoxylin and eosin staining was used to evaluate morphological changes in the liver, pancreas, and adipose tissues around the reproductive organs. Western blotting was carried out to measure the protein expression of IRS-1 and inflammatory factors, including TNF-α, TLR4, MyD88 and phosphorylated NF-κB, in the adipose tissues around the reproductive organs. Puerarin had preventive effects on GDM-induced pathological changes and ameliorated glucose and lipid metabolism disorders in GDM rats. Puerarin upregulated IRS-1 expression and decreased the protein expression of TNF-α, TLR4, and MyD88 as well as the levels of phosphorylated NF-κB in adipose tissues around the reproductive organs in GDM rats. This study indicated that puerarin exerts anti-inflammatory effects by downregulating the important TLR4/MyD88/NF-κB inflammatory signalling pathway. Therefore, puerarin can decrease the expression of TNF-α and ameliorate insulin resistance in GDM rats, suggesting the potential efficacy of puerarin in GDM treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Sara Al-Musharaf ◽  
Shaun Sabico ◽  
Syed Danish Hussain ◽  
Fatima Al-Tawashi ◽  
Haifa Bandar AlWaily ◽  
...  

Objective. To examine differences in maternal serum levels of adipokines (adiponectin, leptin, and resistin) and inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6)) from early to midpregnancy among Arab women with or without gestational diabetes mellitus (GDM), along with their links to GDM risk. Methods. This is a multicenter prospective study involving 232 Saudi women attending obstetric care. Both circulating adipokine and markers of inflammation were observed at the first (eight to 12 weeks) and second trimesters (24 to 28 weeks). GDM was screened at 24 to 28 weeks using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results. Age and body mass index- (BMI-) matched circulating TNF-α was significantly higher in women with GDM in comparison to non-GDM women ( p = 0.01 ). Adiponectin and resistin significantly decreased from the first to second trimester in women without GDM ( p = 0.002 and 0.026, respectively). Leptin presented a significant rise from the first to second trimester in both groups, with a higher increase in women with GDM ( p = 0.013 ). Multivariate logistic regression analysis revealed that TNF-α was significantly correlated with GDM ( p = 0.03 ). However, significance was lost after adjustments for maternal and lifestyle risk factors (OR 23.58 (0.50 to 1119.98), p = 0.11 ). Conclusion. Inflammatory and adipocytokine profiles are altered in Arab women with GDM, TNF-α in particular. Further studies are needed to establish whether maternal inflammatory and adipocytokine profile influence fetal levels in the same manner.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiqi Huang ◽  
Yi Wang ◽  
Binbin Gu ◽  
Yanwen Xu

Abstract Background Whether polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) or adiponectin (ADIPOQ) influence the risk of gestational diabetes mellitus (GDM) or not remain inconclusive. Therefore, the authors conducted a meta-analysis to robustly assess relationships between polymorphisms in TNF-α, IL-6, IL-10 or ADIPOQ and the risk of GDM by merging the results of eligible publications. Methods A through literature searching in Medline, Embase, Wanfang, VIP and CNKI was conducted by the authors to identify eligible publications, and twenty-two publications were finally found to be eligible for merged quantitative analyses. Results The merged quantitative analyses revealed that ADIPOQ + 45T/G (rs2241766) polymorphism was significantly associated with the risk of GDM in overall population (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.95, p < 0.001; over-dominant comparison: OR = 1.18, p = 0.03; allele comparison: OR = 0.71, p < 0.001) and Asians (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.94, p < 0.001; allele comparison: OR = 0.72, p < 0.001). Nevertheless, we did not observe any positive results for TNF-α − 238G/A (rs361525), TNF-α − 308G/A (rs1800629), IL6 − 174G/C (rs1800795), IL-10 − 819C/T (rs1800871), IL-10 − 592C/A (rs1800872), IL-10 − 1082A/G (rs1800896) and ADIPOQ + 276G/T (rs1501299) polymorphisms. Conclusions The present meta-analysis shows that among investigated TNF-α, IL-6, IL-10 or ADIPOQ polymorphisms, only ADIPOQ + 45T/G (rs2241766) polymorphism may affect the risk of GDM.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yucui Teng ◽  
Shuxia Xuan ◽  
Ming Jiang ◽  
Li Tian ◽  
Jinjing Tian ◽  
...  

Background. Gestational diabetes mellitus (GDM) is a severe threat to the health of both mother and child. The pathogenesis of GDM remains unclear, although much research has found that the levels of hydrogen sulfide (H2S) play an important role in complications of pregnancy. Methods. We collected venous blood samples from parturient women and umbilical vein blood (UVB) and peripheral venous blood (PVB) samples one hour after childbirth in the control, GDM-, and GDM+ groups in order to determine the concentration of glucose and H2S in plasma; to measure levels of TNF-α, IL-1β, IL-6, TGF-β1, and ADP in parturient women and the UVB of newborns; and to find the correlation of H2S with regression. Results. We found that, with the elevation of glucose, the level of H2S was decreased in GDM pregnant women and newborns and the concentrations of IL-6 and TNF-α were upregulated. With regression, IL-6 and TNF-α concentrations were positively correlated with the level of blood glucose and negatively correlated with H2S concentration. Conclusion. This study shows that downregulation of H2S participates in the pathogenesis of GDM and is of great significance in understanding the difference of H2S between normal and GDM pregnant women and newborns. This study suggests that IL-6 and TNF-α are correlated with gestational diabetes mellitus. The current study expands the knowledge base regarding H2S and provides new avenues for exploring further the pathogenesis of GDM.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Guanli Zhang ◽  
Xiuli Wang ◽  
Baofeng Ren ◽  
Qiongqiong Zhao ◽  
Fang Zhang

Background. Previous studies have reported that resveratrol has various biological effects such as anti-inflammatory, antioxidant, and antitumor. This study aimed to investigate the effects of resveratrol on blood glucose and blood lipids in rats with gestational diabetes mellitus (GDM). Methods. The rat diabetes model was prepared by one-time intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Fasting blood glucose was measured by using a blood glucose meter. The ELISA method was used to detect the levels of insulin, leptin, adiponectin, resistin, TNF-α, and IL-6. The content of TC, TG, LDL-C, and HDL-C was determined by using an automatic biochemical detector. Results. Compared with the GDM group, the insulin level in the resveratrol (120 and 240 mg/kg) treatment group was significantly increased. But, the blood glucose level and body weight were significantly reduced. The content of TC, TG, and LDL-C in the resveratrol (240 mg/kg) treatment group was significantly reduced, and the content of HDL-C was significantly increased. In addition, leptin, resistin, TNF-α, and IL-6 levels in the 240 mg/kg resveratrol treatment group were significantly reduced, and adiponectin was significantly increased. Also, resveratrol (240 mg/kg) was stronger than metformin hydrochloride in improving insulin secretion and regulating blood lipids and adipokine content. Conclusion. Resveratrol has a dose-dependent effect on GDM rats to increase insulin secretion, reduce blood glucose and body weight, and regulate blood lipids and plasma adipokines.


2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Lei Zhang ◽  
Bi Lu ◽  
Wenhua Wang ◽  
Shifeng Miao ◽  
Shuru Zhou ◽  
...  

Context: Neuregulin 4 (Nrg4) and neuregulin 1 (Nrg1) have been shown to play vital roles in several disorders of glucose metabolism. The pathophysiological role of Nrg4 and Nrg1 in gestational diabetes mellitus (GDM), however, remains poorly understood. We assessed the clinical relevance of the two cytokines in patients with GDM. Methods: The study recruited 36 GDM patients and 38 age-matched, gestational age (24–28 weeks of gestation)–matched, and BMI (during pregnancy)–matched controls in this study. Serum Nrg4 and Nrg1 were measured using ELISA. Inflammatory factors such as IL-6, IL-1β, leptin, TNF-α, and monocyte chemotactic protein 1 (MCP-1) were determined via Luminex technique. Results: Serum Nrg4 in GDM patients was significantly lower than that in the controls, while Nrg1 was significantly higher in the GDM group ( p < 0.01). Inflammatory factors such as IL-6, leptin, and TNF-α were significantly increased in GDM patients, while MCP-1 and IL-1β were not significantly different between the two groups. In addition, serum Nrg4 was negatively correlated with fasting glucose ( r = −0.438, p = 0.008), HOMA-IR ( r = −0.364, p = 0.029), IL-6 ( r = −0.384, p = 0.021), leptin ( r = −0.393, p = 0.018), TNF-α ( r = −0.346, p = 0.039), and MCP-1 ( r = −0.342, p = 0.041), and positively correlated with high-density lipoprotein cholesterol (HDL-C) ( r = −0.357, p = 0.033) in GDM group. Serum Nrg1 was positively correlated with BMI ( r = 0.452, p = 0.006), fasting glucose ( r = 0.424, p = 0.010), HOMA-IR ( r = 0.369, p = 0.027), and triglyceride ( r = 0.439, p = 0.007). The decrease of Nrg4 and the increase of Nrg1 were significantly related to the increased prevalence of GDM. Finally, ROC curve results indicated that Nrg1 combined with IL-6 and TNF-α might be an effective means for GDM screening. Conclusions: Lower circulating Nrg4 and higher circulating Nrg1 serve risk factors of GDM. Nrg1 combined with IL-6 and TNF-α might be a potential tool for GDM screening.


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