Serum levels of copper, zinc and magnesium in pregnant women with Impaired Glucose Tolerance test: A case-control study

Objective: Gestational Diabetes Mellitus (GDM) is a type of diabetes that begins during pregnancy. This problem causes many complications for mother and foetus. Mineral levels in diabetic patients change and since the levels of these elements have not received much attention in patients with Impaired Glucose Tolerance test (IGT), in this study serum concentration of copper (Cu), zinc (Zn), and magnesium (Mg) were analysed in singleton pregnant women with IGT compared with euglycemic pregnant women. Methods: The subjects of this case-control study have been selected from pregnant women who referred to Rohzendeh health and therapeutic center in northwest of Iran from December 2013 - April 2014. 46 pregnant women with IGT and 35 euglycemic women were selected. The levels of hemoglobin, hematocrit, zinc, copper and magnesium in the blood samples were measured. Results: The findings of this study indicated that the difference of hemoglobin and hematocrit and magnesium levels was not significant between two groups. The difference of copper concentration in healthy pregnant women and women with IGT was statistically significant (P<0.001) which indicated a high level of copper in healthy pregnant women. Interestingly, in pregnant women with IGT plasmatic zinc level was lower than healthy women (P= 0.028). Conclusions: Pregnancy is a condition that can affect the mineral status and to achieve better results, further researches are needed with larger sample size. © Mattioli 1885

The effects of zinc supplementation on inflammatory parameters in pregnant women with impaired glucose tolerance: A randomized placebo controlled clinical trial

Pregnancy is hyperglycemic cycle of life and usually associated with insulin resistance from midgestation. Previous studies indicate that abnormal production of some proteins secreted from adipocytes (adipokines) encloses in pathogenesis of insulin resistance and gestational diabetes mellitus (GDM). It is proven that maternal zinc deficiency affects glucose metabolism, but the interaction between zinc and adipokines secretion are not well understood. This study aims to evaluate the effect of zinc supplementation on Vaspin and IL-6 levels in pregnant women with impaired glucose tolerance (IGT). In this matched, placebo controlled double blind clinical trial, 46 pregnant women with impaired glucose tolerance were randomly distributed to zinc (n=23) and placebo (n=23) groups and received 30 mg/day zinc gluconate or placebo for eight regular weeks. The study was conducted in Shabestar district, North West of Iran. Serum Vaspin and IL-6 levels were assessed before and after intervention. There was a significant decrease in Vaspin and IL-6 levels in zinc group (p= 0.004, p= 0.034, respectively). Further, changes in fasting Vaspin levels had a positive correlation with change in fasting IL-6 levels in both zinc (r= + 0.820, p<0.001) and placebo (r= + 1.000, p<0.001) groups. According to enhancement of inflammatory cytokines in pregnant women with IGT, zinc may be considered as a complimentary supplement together with medical management in patients with IGT and GDM. However, further studies with greater sample size and extended periods of intervention are needed to make definite conclusion. © Mattioli 1885

The effects of sodium butyrate and high-performance inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in miR-375 and KLF5 expression in type 2 diabetic patients: A randomized, double-blind, placebo-controlled trial

Introduction: The aim of this study is to evaluate the effect of sodium butyrate and High-Performance (HP) inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in microRNA-375 and Krüppel-like factor 5 (KLF5) expression in patients with T2D. Methods: In this clinical trial, 60 patients with T2D were recruited and randomly allocated into four groups of equal size to receive 600 mg/day sodium butyrate (Group A), 10 g/day inulin powder (Group B), concomitant use of inulin and sodium butyrate (Group C), or placebo (Group D). Blood and stool samples were collected pre- and post-intervention. Quantitative real-time PCR analysis targeting the 16S rRNA gene of A.muciniphila was performed to determine its presence in the patient's stool. In addition, we assessed the KLF5 mRNA expression and the plasmatic level of the microRNA-375 before and after the intervention. Results: The results showed that A. muciniphila percent change increased significantly after supplementation with HP inulin (p = 0.017) and butyrate (p = 0.036). Also, supplementation with HP inulin significantly decreased the KLF5 fold change after intervention (fold change 0.42 ± 0.15, p = 0.037). In particular, in comparison to the placebo group, an increased expression of miR-375 was seen after butyrate and butyrate+ inulin supplementation (P = 0.003 and P = 0.007 respectively). Conclusions: We concluded that inulin and butyrate may potentially promote gut health and can be considered as novel therapeutic approache for the prevention and control of diabetes. © 2018 Elsevier Gmb

The effects of sodium butyrate and high-performance inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in miR-375 and KLF5 expression in type 2 diabetic patients: A randomized, double-blind, placebo-controlled trial

Introduction: The aim of this study is to evaluate the effect of sodium butyrate and High-Performance (HP) inulin supplementation on the promotion of gut bacterium Akkermansia muciniphila growth and alterations in microRNA-375 and Krüppel-like factor 5 (KLF5) expression in patients with T2D. Methods: In this clinical trial, 60 patients with T2D were recruited and randomly allocated into four groups of equal size to receive 600 mg/day sodium butyrate (Group A), 10 g/day inulin powder (Group B), concomitant use of inulin and sodium butyrate (Group C), or placebo (Group D). Blood and stool samples were collected pre- and post-intervention. Quantitative real-time PCR analysis targeting the 16S rRNA gene of A.muciniphila was performed to determine its presence in the patient's stool. In addition, we assessed the KLF5 mRNA expression and the plasmatic level of the microRNA-375 before and after the intervention. Results: The results showed that A. muciniphila percent change increased significantly after supplementation with HP inulin (p = 0.017) and butyrate (p = 0.036). Also, supplementation with HP inulin significantly decreased the KLF5 fold change after intervention (fold change 0.42 ± 0.15, p = 0.037). In particular, in comparison to the placebo group, an increased expression of miR-375 was seen after butyrate and butyrate+ inulin supplementation (P = 0.003 and P = 0.007 respectively). Conclusions: We concluded that inulin and butyrate may potentially promote gut health and can be considered as novel therapeutic approache for the prevention and control of diabetes. © 2018 Elsevier Gmb

Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study

Background: New evidence indicates that overproduction of pro-inflammatory cytokines is responsible for the development of diabetes difficulties. Some herbals such as saffron, may control inflammation and improve the hyperglycemic states in diabetic patients. Therefore, this investigation aimed to assess the effects of saffron supplementation on fasting glucose and inflammatory markers levels in patients with type2 diabetes mellitus (T2DM). Methods: In this randomized double-blind, placebo-controlled clinical trial, 60 T2DM patients were randomly assigned into two groups as saffron and placebo (n = 30) receiving 100 mg/day saffron powder or starch capsules (1 capsule) for a duration of 8 weeks. Fasting blood sample was collected at baseline and at the end of the intervention. Fasting blood glucose (FBG) was immediately analyzed by the auto-analyzer. The serum level of Interleukin �6 (IL-6), Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) were measured using ELISA assay by laboratory kits. Also, Real-time quantitative reverse transcription (RT-PCR) assay measured the expression level of TNF-α, IL-6, and IL-10 at the mRNA level. Results: Saffron supplementation significantly decreased the FBG levels within 8 weeks compared to placebo (130.93 ± 21.21 vs 135.13 ± 23.03 mg/dl, P = 0.012). Moreover, the serum level of TNF-α notably reduced in the saffron group compared to the placebo group (114.40 ± 24.28 vs 140.90 ± 25.49 pg/ml, P < 0.001). Also, saffron supplementation significantly down-regulated the expressions of TNF-α (P = 0.035) and IL-6 mRNA levels (P = 0.014). Conclusion: In our study, it was indicated that saffron modulates glucose levels as well as inflammation status in T2DM patients through decreasing the expressions levels of some inflammatory mediators. Also, further investigations are necessary to confirm the positive effects of saffron as a complementary therapy for T2DM patients. © 2020 Diabetes Indi

The suppression of TXNIP and miR-200c improve beta-cell function in patients with Type 2 diabetes: A randomized, double-blind, placebo-controlled trial

The past decade has witnessed for high prevalence of various metabolic, lifestyle, and diet-related maladies such as diabetes. Currently, one of the new treatment methods and approaches for controlling chronic degenerative diseases such as diabetes is dissecting the disease's molecular mechanisms. The aim of this study was to evaluate the beneficial effects of sodium butyrate and inulin supplementation on the beta-cell function and inflammatory responses through molecule-based mechanisms in patients with Type 2 diabetes. In this clinical trial, 60 patients with Type 2 diabetes were recruited from the north-western part of Iran. The participants were allocated to one of the four treatment orders. Group A took six capsules of 100 mg of NaBut daily, group B took 10 g of HP inulin supplement powder daily, group C consumed both the supplements, and group D took placebo. Before and after the intervention, we assessed the thioredoxin-interacting protein (TXNIP), interleukin-6, and interleukin-10 mRNA expression, as well as noting the plasmatic levels of the miR-204, miR-200c, and miR-21. A homeostasis model assessment of beta-cells (HOMA-β) was used to evaluate the function of the pancreatic beta-cells. The results showed that TXNIP expression was over three times higher in the placebo group as compared to the butyrate + inulin group (p = 0.045). Furthermore, the plasmatic levels of miR-200c expression decreased in the groups A (butyrate) and C (butyrate + inulin) (p < 0.001), as opposed to its constant level in the placebo. Interestingly, IL-6 mRNA expression decreased after butyrate (p < 0.001) and butyrate + inulin supplementation (p < 0.001). Our results revealed new insights into how TXNIP functions have a role in controlling diabetes. The newly identified TXNIP-miR-200c-IL-6-beta-cell function pathway may contribute to diabetes progression. Inhibiting TXNIP and miR-200c activity may be a potential pharmacological target to promote beta-cell function. © 2018 Elsevier Lt

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial

Purpose: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). Methods: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). Results: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1β & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. Conclusion: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link. © 202

A novel inflammatory signaling pathway in patients with slow coronary flow: NF-κB/IL-1β/nitric oxide

Purpose: The slow coronary flow (SCF) was identified as delayed opacification of epicardial coronary arteries in the absence of stenotic lesion. Metabolic syndrome (MetS), oxidative stress, and inflammation may be possible known insulting factors for the pathogenesis of SCF. This investigation aimed to assess the relationship between some inflammatory markers, oxidative stress parameters and MetS components with SCF phenomenon. Methods: A total of 35 patients with SCF and 35 subjects with normal coronary flow (NCF) were included in the study. We assessed some inflammatory markers (IL-1β, IL-18, TNF-α, and NF-κB mRNA expression in peripheral blood mononuclear cells (PBMCs)). Moreover, blood samples of the participants were tested for total antioxidant capacity (TAC), glutathione peroxidase (GPX) and nitric oxide (NO) levels using enzyme-linked immunosorbent assay (ELISA). Diagnosis of MetS was based on the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII) criteria, 2005. Diagnostic criteria for coronary flow rates of all subjects were documented by thrombolysis in myocardial infarction (TIMI) frame count method. Results: SCF patients had significantly higher prevalence of MetS (46, p = 0.048).We found that the level of TAC was significantly higher in the NCF group (p = 0.006). Furthermore, the NO concentration was significantly lower in SCF groups (p = 0.001). A significant incremental difference was detected in IL-1β (fold change 2.82 ± 0.31, p < 0.05) and NF-κB (fold change 4.62 ± 0.32, p < 0.05) mRNA expression in the SCF group when compared with its level in the NCF group. Furthermore, according to logistic regression analysis, there were significant associations between IL-1β, NF-κB expression levels and the incidence of SCF (p < 0.05). Conclusion: Based on the findings of this study, the pathogenesis of the SCF phenomenon may be closely associated with metabolic syndrome and inflammation. The NF-κB/IL-1β/nitric oxide & MetS signaling pathway might be considered as potential therapeutic targets in the management of SCF patients but further researches is required to guarantee these findings. © 2021 Elsevier Lt