Excessive gestational weight gain in the first trimester is associated with risk of gestational diabetes mellitus: a prospective study from Southwest China.

OBJECTIVE: To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women. DESIGN: A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range. SETTING: Southwest China. PARTICIPANTS: Pregnant women (n 1910) in 2017. RESULTS: After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8-1·2, 0·8-1·2 and 0·35-0·70 kg for underweight, normal-weight and overweight/obese women, respectively. CONCLUSIONS: Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.

[A Prospective Study of the Relationship Between Dietary Patterns during the Second Trimester of Pregnancy and Gestational Weight Gain].

OBJECTIVE: To study dietary patterns during the second trimester of pregnancy and to investigate the relationship between dietary patterns and gestational weight gain (GWG). METHODS: A prospective cohort study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and child health care institution in Chengdu city. Food items and quantities were collected at 8-14, 24-28, 32-36 weeks of gestation by using the 3-day 24-hour dietary recall and energy intakes were calculated. Dietary patterns during the second trimester were established by factor analysis and factor scores were calculated. The weight of pregnant women was measured at 8-14, 24-28 weeks of gestation and 1 week before delivery, and the total GWG and the GWG rates in the second and third trimesters were calculated. Multiple linear regression analyses were used to analyze the association between dietary patterns and GWG. RESULTS: A total of 1 004 samples were included. Three dietary patterns were identified: Milk-egg-whole grain pattern, Beverage-dessert pattern and Traditional pattern. The average total GWG was (13.2±4.5) kg. The average weight gain rate was (0.4±0.2) kg/week in the second trimester. The average weight gain rate was (0.5±0.3) kg/week in the third trimester. After adjusting for confounding factors including maternal age, body mass index before pregnancy, dietary energy intake, physical activity, multiple linear regression analysis showed that the factor score of Beverage-dessert pattern was positively associated with the total GWG and the weight gain rate in the third trimester ( ß=0.370, 95% confidence interval ( CI): (0.103, 0.636), P=0.007; ß=0.014, 95% CI: (0.000, 0.027), P=0.049, respectively), and the factor score of Traditional pattern was negatively associated with the total GWG ( ß=-0.285, 95% CI: (-0.555, -0.015), P=0.039). There was no association between the Milk-egg-whole grain pattern and GWG. CONCLUSION: Dietary patterns during the second trimester of pregnancy are associated with GWG. The Beverage-dessert pattern may increase the total GWG and weight gain rate in the third trimester. The traditional pattern may help control the total GWG.

[Associations of Dairy Consumption during Pregnancy and Neonatal Birth Body Mass: a Prospective Study].

OBJECTIVE: To investigate the dairy product intake during pregnancy in Southwest China and to explore its relationship with neonatal birth body mass. METHODS: A prospective study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and fetal health care institution in Chengdu City. Dairy product consumption during the first, second, third trimester of pregnancy were collected by 24-hour dietary recalls at 8-14 weeks, 24-28 weeks and 32-36 weeks of pregnancy, respectively, and the total milk intake and milk consumption rate were calculated. According to the dietary guidelines for Chinese pregnant women (2016), the recommended amount of milk (300 g/d) was used as the standard to calculate the compliance rate. The respondents were divided into three groups: no dairy consumption group, insufficient dairy consumption group and suitable dairy consumption group. The gestational age at delivery and neonatal birth body mass were collected by the hospital information system. Logistic regression model was used to analyze the association between milk intake during pregnancy and neonatal birth body mass. RESULTS: A total of 962 pregnant women were included. The average milk intake in the first, second and third trimester of pregnancy were 125.0 (0, 236.1) g/d, 208.3 (0, 284.7) g/d and 250.0 (150.0, 416.7) g/d, respectively, with the compliance rates of 12.6%, 33.2% and 48.4%, respectively. The average neonatal birth body mass was (3 225.0±399.8) g. The incidence of small for gestational age (SGA) and large for gestational age (LGA) was 8.3% and 3.9%, respectively. Compared with no dairy consumption group in the second trimester of pregnancy, the risk of SGA was lower in suitable dairy consumption group (odds ratio (OR)=0.786, 95% confidence interval (CI): 0.385-0.976). Compared with no dairy consumption group in the third trimester of pregnancy, the risk of SGA was lower in insufficient dairy consumption group and suitable dairy consumption group (OR=0.672, 95%CI: 0.477-0.821 and OR=0.497, 95%CI: 0.116-0.807, respectively). No association was observed between milk intake in the first trimester and neonatal birth body mass, and milk intake in the second and third trimester of pregnancy was not associated with the risk of LGA. CONCLUSION: Insufficient milk intake of pregnant women is a significant problem in southwest China and needs to be improved. Milk intake during pregnancy is associated with neonatal birth body mass, and increased milk intake in the second and third trimester of pregnancy may reduce the risk of SGA.

Visfatin regulates the production of lipopolysaccharide-induced inflammatory cytokines through p38 signaling in murine macrophages.

Visfatin plays an important role in regulation of inflammatory cytokines. However, the role of visfatin under bacterial stress condition is not fully explored yet. Therefore, the present study was conducted for the better understanding of the regulation mechanism of visfatin on the production of inflammatory cytokines under lipopolysaccharide (LPS) stress in RAW264.7 murine macrophages. Enzyme Linked Immuno-sorbent Assay (ELISA) results showed that, as compared to the control group, visfatin significantly up-regulated the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α (P < 0.05). Compared to the LPS group, the levels of IL-1ß, IL-10, TNF-α was down-regulated in visfatin + LPS group (P < 0.05). After adding p38 inhibitor, SB203580 to culture, the production of IL-1ß, IL-6, IL-10, TNF-α was significantly reduced as compared to visfatin only (P < 0.01). The results showed that visfatin may regulate the production of IL-1ß, IL-6, IL-10, TNF-α through the p38 signaling pathway. As compared to the PBS group, phosphorylayed p38 (P-p38) level in visfatin group was significantly decreased (P < 0.05). Compared with LPS group, P-p38 level was significantly decreased in visfatin + LPS group (P < 0.05). Hence, it is concluded that visfatin can significantly increase the levels of IL-1ß, IL-10 and TNF-α in normal conditions, while their levels significantly decrease during inflammation. Moreover, visfatin participates in the inflammatory response through the p38 mitogen-activated protein kinase (MAPK) signal pathway by the up-regulation of p38 and down-regulation of P-p38 levels.

Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice.

BACKGROUND/AIMS: Urotensin II (UII) and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN). The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress) and Epithelial-mesenchymal transition (EMT) in DN in vivo and in vitro. METHODS: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. RESULTS: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1), fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. CONCLUSIONS: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients.

AIMS/INTRODUCTION: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. MATERIALS AND METHODS: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. CONCLUSIONS: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

Starchy vegetable intake in the first trimester is associated with a higher risk of gestational diabetes mellitus: a prospective population-based study.

OBJECTIVE: The purpose of this study was to evaluate the association between starchy vegetable consumption and subgroup consumption in the first trimester and the risk of gestational diabetes mellitus (GDM). METHODS: A prospective study (n = 1444) was conducted in China. Dietary information was assessed by 24-hour dietary recalls for three days and then we calculated the consumption of total starchy vegetable and its subgroups, including (1) potato and (2) other starchy vegetable (pumpkin, lotus root, yam, taro, water chestnut, pea, and cowpea). GDM was diagnosed according to the results of 75-g two-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. A modified log-binomial regression was used to estimate RRs and 95% CIs of GDM risk. RESULTS: Among the 1444 participants in our study, 520 were diagnosed with GDM. The adjusted RRs (95% CIs) for GDM from the lowest to the highest quartiles of total starchy vegetable consumption were 1.00 (reference), 1.29 (1.06, 1.57), 1.13 (0.93, 1.40), and 1.26 (1.02, 1.56), respectively; p for trend = .032. For potato, the RR of GDM risk was 1.32 for the highest potato intake quartile compared with the lowest quartile (95% CI 1.07-1.64, p for trend = .003). In addition, we did not observe an association between other starchy vegetable intakes and GDM risk. CONCLUSIONS: A higher consumption of total starchy vegetables and potatoes in the first trimester is associated with a greater risk of GDM.

Visfatin Regulates Inflammatory Mediators in Mouse Intestinal Mucosa Through Toll-Like Receptors Signaling Under Lipopolysaccharide Stress.

Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1ß, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.

Visfatin Exerts Immunotherapeutic Effects in Lipopolysaccharide-Induced Acute Lung Injury in Murine Model.

Visfatin acts as a significant regulator of inflammatory cytokines. However, the immunological response and therapeutic effects of visfatin under bacterial stress in murine lung tissue are still not clear. To investigate the role of visfatin on lipopolysaccharide (LPS)-induced acute lung injury (ALI), thirty Kunming mice were divided into Saline, LPS, and LPS + visfatin groups. After routine blood examination, the effects of visfatin on inflammatory cytokines, lung tissue structure, and expression of inflammatory mediators were explored through hematoxylin-eosin (H&E), Masson and immunohistochemical staining, quantitative polymerase chain reaction (Q-PCR), and Western blotting. Compared with the Saline group, neutrophil percentage, peripheral blood neutrophil count, and the ratio of lymphocyte count (NLR) were upregulated in LPS group. Moreover, Masson staining showed alterations in lung tissue structure; the mRNA level of different cytokines (IL-6, IL-1ß, TNF-α, IL-10, TLR4, IFN-γ) was upregulated; and the protein expression of interleukin (IL)-6, myeloperoxidase (MPO), and transforming growth factor-ß1 (TGF-ß) was significantly (p < 0.05) different in LPS group. Compared with LPS group, neutrophil percentage significantly decreased (p < 0.01), the numbers of lymphocytes significantly (p < 0.05) increased, NLR decreased, Masson staining of the lung was extremely different (p < 0.01), the structure of the lung was slightly damaged, and the myeloperoxidase values of lung showed no differences in LPS + visfatin. Hence, visfatin inhibits the lung inflammation induced by ALI. During the ALI, visfatin acts by decreasing NLR, downregulated the expression of MPO, enhanced antioxidant capacity, and regulated the inflammatory factors IL-1ß, IL-6, IL-10, and TNF-α to reduce the lung injury.

Visfatin Plays a Significant Role in Alleviating Lipopolysaccharide-Induced Apoptosis and Autophagy Through PI3K/AKT Signaling Pathway During Acute Lung Injury in Mice.

Visfatin is involved in the body's inflammation and immune response. Inflammation could promote, while visfatin may directly or indirectly mitigate the effects of apoptosis and autophagy. Whether visfatin lessens the detrimental effects of lipopolysaccharide (LPS)-induced mouse acute lung injury (ALI) is poorly understood yet. Therefore, in the current study, the regulation mechanism of visfatin on apoptosis and autophagy was explored in Kunming mice by replicating LPS-induced inflammatory ALI model. Based on the mouse model of ALI, HE staining, TUNEL, transmission electron microscopy, immunohistochemical staining, real-time fluorescence quantitative PCR and western blot were used and the results showed that the alveolar septum was thinner than that of the LPS group, slight lung interstitial and alveolar exudation appeared, and a small number of inflammatory cell infiltration was found in the visfatin intervention group, indicating reduced tissue damage in lungs. After visfatin treatment, the expression of pro-apoptotic genes Bax, Bik, and p53 decreased and the expression of anti-apoptotic genes Bcl-2 and Bcl-xl increased, and expression of autophagy factors LC3 and Beclin1 decreased, indicating that visfatin inhibits apoptosis and reduces autophagy. The expression of PI3K and p-AKT was upregulated in the visfatin intervention group, the expression of AKT was downregulated, and the PI3K/AKT signaling pathway was activated. Hence, visfatin could activate the PI3K/AKT signaling pathway, reduce the apoptotic rate in alveolar epithelial cells and the level of autophagy in ALI by regulating the expression of autophagy factors, ultimately causing a protective effect on lung tissue.

FGF-21 Elevated IL-10 Production to Correct LPS-Induced Inflammation.

Fibroblast growth factor 21 (FGF-21) has been previously judged as a major metabolic regulator. In this paper, we show that FGF-21 has a potential role in anti-inflammation and immunoregulation. In vivo, treatment with exogenous FGF-21 can alleviate LPS-induced inflammation. In vitro, FGF-21 inhibited LPS-induced IL-1ß expression in THP-1 cells. Furthermore, besides the NF-κB pathway, the mechanism of action of FGF-21 was observed to involve the elevation of IL-10 in the ERK1/2 pathway. This study clearly indicates that FGF21 can be used as an attractive target for the management of inflammatory disorders. This piece of research indicates that FGF-21 could have much value in the management of inflammatory disorders.

Retraction statement: 'Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice' by Guan­Jong Chen, Fei Wu, Xin­Xin Pang, Ai­Hua Zhang, Jun­Bao Shi, Min Lu and Chao­Shu Tang

AIMS/INTRODUCTION: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. MATERIALS AND METHODS: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10-7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10-6 mol/L) or autophagy inducer, rapamycin (10-3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. RESULTS: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV. CONCLUSIONS: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.