Suppression of Growth Differentiation Factor 15 Gene Expression by Curcumin in Patients with Beta-Thalassemia Intermedia.

BACKGROUND: ß-thalassemia is an inherited disorder caused by defects in the synthesis of the beta-globin chain. One of the significant clinical complications in ß-thalassemia intermedia is iron overload toxicity, which may be attributed to reduced levels of hepcidin. This reduction in hepcidin leads to increased absorption of iron in the intestines, ultimately resulting in iron overload. The objective of this study was to assess the impact of curcumin on the expression of growth differentiating factor-15 (GDF-15) and hepcidin genes in patients with beta-thalassemia intermedia. METHODS: This study was designed as a randomized controlled double-blind clinical trial. Prior to and after the intervention period with curcumin, a blood sample of 5 mL was collected from both the placebo and curcumin-treated groups for the assessment of hepcidin and growth differentiating factor-15 gene expression. RESULTS: This study revealed a significant reduction in the expression of growth differentiating factor-15 in the curcumin group compared to the placebo group during the 3-month treatment period. Furthermore, curcumin supplementation led to a remarkable 10.1-fold increase in the levels of hepcidin in the curcumin group compared to the placebo group. CONCLUSIONS: The results of this study show that curcumin administration increases the mRNA levels of hepcidin in whole blood of thalassemia intermedia patients and supports the idea that curcumin could be a potential treatment to reduce suppression of hepcidin in thalassemias and other iron-loading anemias. CONCLUSIONS: The results of this study show that curcumin administration increases the mRNA levels of hepcidin in whole blood of thalassemia intermedia patients and supports the idea that curcumin could be a potential treatment to reduce suppression of hepcidin in thalassemias and other iron-loading anemias.

Up-regulated lncRNA-PVT1 expression in peripheral blood mononuclear cells of patients with coronary artery disease is correlated with decreased interleukin-10 production.

OBJECTIVES: Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA, which has not been previously studied in the inflammatory responses of the peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). MATERIALS AND METHODS: This cross-sectional study was conducted on 15 CAD patients and 15 non-CAD (NCAD) individuals. The PVT1 expression was assessed in the PBMCs of the participants using a real-time polymerase chain reaction. Interleukin (IL)-10, IL-22, and matrix metalloproteinase-9 (MMP-9) were measured in the plasma and supernatant of cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: An increased expression of PVT1 was observed in the untreated PBMCs of CAD patients, compared to the NCAD group. The PVT1 was significantly up-regulated after LPS treatment in the PBMCs of both groups. Plasma MMP-9 levels were found to be higher in CAD patients than in the control individuals. The level of IL-10 and IL-22 production by the non-treated PBMCs of CAD cases was significantly lower than the NCAD group. Overall, in the examined population, PVT1 expression was negatively correlated with IL-10 secretion. Moreover, the results showed a significant negative correlation between PVT1 expression and IL-10 production by untreated cells. CONCLUSIONS: The PVT1 expression augmented in the PBMCs of CAD patients, which could be associated with the decreased IL-10 generation by the PBMCs of these patients.

The Effect of Curcumin on Iron Overload in Patients with Beta-Thalassemia Intermedia.

BACKGROUND: ß-thalassemia is an inherited disorder that stems from a defect in beta-globin chain synthesis. Iron overload toxicity is one of the major clinical complications in ß-thalassemia that may be due to a reduction in the hepcidin level. As a result, intestinal iron absorption increases and finally iron overload occurs. The current study aimed to investigate the effect of curcumin on serum iron status, ferritin, and transferrin in patients with ß-thalas-semia intermedia. METHODS: This study was a randomized, controlled, double-blind clinical trial. Before and after the intervention period with curcumin, 5 ml blood was taken for the measurement of the entire index related to iron status. RESULTS: Our results demonstrated the levels of serum iron (p-value < 0.001), ferritin (p-value = 0.002), and transferrin saturation (p-value < 0.001) significantly decreased in the curcumin group compared to placebo. CONCLUSIONS: The data presented in this article show that curcumin supplementation would be effective in alleviating iron overload in patients with ß-thalassemia intermedia.

The effect of curcumin on serum copper, zinc, and zinc/copper ratio in patients with ß-thalassemia intermedia: a randomized double-blind clinical trial.

Thalassemia intermedia is a subgroup of ß-thalassemia which originates from mutations in the beta-globin gene. Zinc and copper play important roles in the metabolism. Due to its significant therapeutic effects, curcumin has led many studies to focus on curcumin. In a double-blind clinical trial study, 30 patients with beta-thalassemia intermedia with an age range of 20 to 35 years were randomly selected 1:1 to receive either curcumin or placebo for 3 months. Before and after the intervention period, 5 ml of blood was taken to determine the serum levels of zinc and copper. The laboratory tests were checked at baseline and at the end of the treatment. While the serum levels of zinc and zinc/copper significantly increased, the serum levels of copper decreased after 3 months of curcumin intake. In addition, on the basis of baseline characteristics, a negative correlation was found between zinc and body mass index and positive correlations were identified between copper with triglyceride and high-density lipoprotein. Also, the level of ferritin protein in the curcumin group compared to the placebo group showed a significant decrease after 3 months of curcumin use. Therefore, it could be concluded that curcumin might exert a net protective effect on copper toxicity in thalassemia intermedia patients. The investigation also implicated that curcumin represents an approach to regulating zinc homeostasis and may be useful as a complementary treatment of patients with thalassemia intermedia, especially in patients with zinc deficiency or low serum zinc/copper ratio. Clinical Trial Registration Number: IRCT20190902044668N1.

Effects of garlic extract on lipid profile in patients with coronary artery disease: A systematic review and meta-analysis of randomised clinical trials.

This meta-analysis was conducted to evaluate the effects of garlic extract on total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c), among the patients with coronary artery disease (CAD). Literature searches were conducted in EMBASE, Scopus, PubMed, Web of Science and Cochrane Library until Sep18th, 2020. Inter-study heterogeneity was examined using Cochrane's Q and I2 tests. The random-effect models were utilised to pool the weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Six articles were enrolled in the current meta-analysis. Garlic consumption significantly reduced TC levels (WMD -16.32 mg/dL; 95% CI -31.22, -1.43; P = .032). We found no significant effects on TG (WMD -10.93 mg/dL; 95% CI -26.19, 4.32; P = .160), HDL-c (WMD 4.55 mg/dL; 95% CI -1.13, 10.23; P = .116) and LDL-c concentrations (WMD -3.65 mg/dL; 95% CI -13.21, 5.92; P = .455). Significant heterogeneity was observed for HDL-c (I2  = 76.8%). However, the findings of sensitivity analysis revealed that upon exclusion of the potential heterogeneity source, the pooled WMD on HDL-c levels were stable. Garlic supplementation may result in a decrease in TC, but will not affect TG, HDL-c and LDL-c levels among CAD patients.

Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence on low serum vitamin-D levels and the risk of uterine leiomyomas (UL). Therefore, this systematic review and meta-analysis was conducted to investigate the association between serum vitamin D levels and UL occurrence. METHODS: Searches were systematically conducted of the electronic databases PubMed, Scopus, EMBASE, Web of Science (ISI), Cochrane library, Ovid, and Google Scholar to identify relevant studies from inception until February 6, 2020. Heterogeneity across the included studies was examined using Cochran's Q and I-square (I2). Data was pooled using random effects modeling and expressed as standardized mean differences (SMDs). RESULTS: Nine eligible studies with a total of 1730 participants (835 patients with UL and 895 controls) were included in the current meta-analysis. Pooled results with random effects modeling indicated that serum vitamin D levels were significantly lower in patients with UL than in the control group (n = 9, SMD = - 0.67; 95% CI, - 0.98, - 0.35, p < 0.001; I2 = 89.3%, p < 0.001). Based on the findings of subgroup analyses, it was found that the SMD values across the included studies from Asia (n = 4, SMD = - 1.20; 95% CI, - 1.45, - 0.96, p < 0.001; I2 = 30.6%, p = 0.229) were lower than those from Europe (n = 3, SMD = - 0.34; 95% CI, - 0.49, - 0.18, p < 0.001; I2 = 0.0%, p = 0.602) and Africa (n = 2, SMD = - 0.13; 95% CI, - 0.29, 0.04, p = 0.128; I2 = 0.0%, p = 0.417), although the difference was not significant in Africa. Publication year was also found to be a potential contributor's variable in the pooled SMD using the meta-regression method (t = - 3.00, p = 0.02). CONCLUSIONS: To the best of our knowledge, the current meta-analysis showed for the first time that serum vitamin D levels were significantly lower in women with UL in selected populations.

The effect of voglibose on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: The effect of voglibose on metabolic homeostasis is not well characterized. Therefore, we conducted a systematic review and meta-analysis of clinical trials assessing the effect of voglibose on metabolic profile in patients with type 2 diabetes mellitus (T2DM). METHODS: Systematic searches were conducted in PubMed, Scopus, Embase, Google Scholar, Web of Science and Cochrane Library to identify clinical trials assessing the effects of voglibose supplementation on cardio-metabolic profile from incept up to 29 July 2019. Data was pooled using fixed- or random-effect models and weighted mean difference (WMD) as the effect size. RESULTS: Eight clinical trials from 1094 reports, were eligible for inclusion. Pooled findings identified significant reductions in hemoglobin A1c (HbA1c) (WMD= -0.27; 95 %CI -0.49 to -0.05; P = 0.01; I2 = 64.8 %) and an increase in LDL-cholesterol levels (WMD=5.97 mg/dl, 95 % CI 0.88, 11.06, P = 0.02; I2 = 0.0 %). However, no evidence of effect for voglibose intake on T2DM patients was observed for: fasting blood sugar (FBS) (WMD -7.43 mg/dl; 95 %CI -16.56 to 1.71; P = 0.110; I2 = 69.3 %), serum insulin (WMD= -0.15 µU/mL; 95 %CI -0.89 to 0.60; P = 0.70; I2 = 0.0 %), total-cholesterol (WMD=2.82 mg/dl, 95 %CI -2.36 to 8.01, P = 0.70; I2 = 49.7 %), triglycerides (WMD= -7.07 mg/dl, 95 %CI -21.76 to 7.62, P = 0.34; I2 = 0.0 %), HDL-cholesterol levels (WMD= -2.10 mg/dl, 95 %CI -4.48 to 0.27, P = 0.08; I2 = 0.0 %,), body mass index (BMI) (WMD=0.09 kg/m2, 95 %CI -0.70 to 0.87; P = 0.87; I2 = 0.0 %), body weight (WMD= -0.42 kg, 95 %CI -0.84 to 0.00; P = 0.05; I2 = 0.0 %), and adiponectin levels (WMD = 0.32 µg/mL, 95 %CI -0.74 to 1.38; P = 0.55; I2 = 0.0 %). CONCLUSIONS: The current meta-analysis identified a decrease in HbA1c and an increase in LDL-cholesterol with administration of voglibose. However, no significant effect was observed on FBS, insulin, bodyweight, BMI, adiponectin, triglycerides, total- and HDL-cholesterol levels.

Effects of Ginkgo biloba intake on cardiometabolic parameters in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials.

Ginkgo biloba (GKB) may have a beneficial effect on cardiometabolic parameters in type 2 diabetes mellitus (T2DM), but the data is inconsistent. Therefore, the current systematic review and meta-analysis of clinical trials was conducted to assess the influence of GKB on cardiometabolic parameters in T2DM. Several online databases such as PubMed, Embase, Scopus, Web of Sciences, Google Scholar and Cochrane Library were systematically searched from inception up to September 2, 2019. Heterogeneity across included studies was assessed using the Cochran's Q statistic and I2 index. To pool weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs) as summary effect size, we selected fixed or random-effects model according to the result of heterogeneity. Seven studies comprising 768 subjects were included in the present meta-analysis which resulted in a significant effect of GKB on hemoglobin A1c (HbA1c) (WMD = 0.26, 95% CI = [0.02, 0.50], p = .034) and serum HDL-cholesterol levels (WMD = 1.99, 95% CI = [0.19, 3.79], p = .030) with no significant publication bias. GKB can significantly modulate HbA1c and HDL-cholesterol levels. However, due to uncertainties related to the limited number of studies, it is too early to conclude whether GKB has any potential effects on the cardiometabolic factors in patients with T2DM or not.

The effects of aerobic and resistant exercises on the lipid profile in healthy women: a systematic review and meta-analysis.

Exercise can have a wide range of health benefits, including improving blood lipid profiles. For women to achieve optimal cardiovascular health, it is vital to determine the effect of exercise on their health and whether different exercise intensities can affect their blood lipid profile. A systematic review and meta-analysis were conducted to examine the effects of exercise on improving the lipid profile of healthy women. A database search was conducted using PubMed, Google Scholar, Embase, Scopus, and Web of Science from inception until July 2, 2021, for randomized controlled trials (RCTs) investigating exercise's effects on healthy women's blood lipid profiles. A total of 10 eligible articles (or 17 trials) with 576 participants were identified as eligible for the study. Overall, the meta-analysis shows that physical activity significantly improved total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL-C) levels: TC [WMD = -5.77 mg/dL, 95% CI: -10.41, -1.13, P < 0.01]; TG [WMD = -5.60 mg/dL, 95% CI: -8.96, -2.23, P < 0.01]; HDL [WMD = 4.49 mg/dL, 95% CI: 0.33, 8.65, P = 0.03]. Additionally, sub-group analyses indicated that combined exercise training improved TG and TC (p 0.05), and aerobic exercise significantly increased HDL. In this study, physical activity appears to be one of the most effective non-pharmacological means for improving HDL, TG, and TC in healthy women. In terms of TG and TC, CT was the most effective.

Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis.

The aim of this meta-analysis was to investigate whether the blood concentrations of patients with multiple sclerosis (MS) are associated with those of the healthy control group in terms of trace elements including zinc (Zn), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), and copper (Cu). A comprehensive search was performed in online databases including PubMed, Scopus, Embase, and Web of Science for studies, which have addressed trace elements in MS up to July 23, 2020. The chi-square test and I2 statistic were utilized to evaluate inter-study heterogeneity across the included studies. Weighted mean differences (WMDs) and corresponding 95% CI were considered as a pooled effect size (ES). Twenty-seven articles (or 32 studies) with a total sample comprised of 2895 participants (MS patients (n = 1567) and controls (n = 1328)) were included. Pooled results using random-effects model indicated that the levels of Zn (WMD = - 7.83 mcg/dl, 95% CI = - 12.78 to - 2.87, Z = 3.09, P = 0.002), and Fe (WMD = - 13.66 mcg/dl, 95% CI = - 23.13 to - 4.19, Z = 2.83, P = 0.005) were significantly lower in MS patients than in controls. However, it was found that levels of Mn (WMD = 0.03 mcg/dl, 95% CI = 0.01 to 0.04, Z = 2.89, P = 0.004) were significantly higher in MS patients. Yet, no significant differences were observed in the levels of Mg, Se, and Cu between both groups. This meta-analysis revealed that the circulating levels of Zn and Fe were significantly lower in MS patients and that Mn level was significantly higher than those in the control group. However, it was found that there was no significant difference between MS patients and controls with regard to levels of Mg, Se, and Cu.

The effects of beraprost sodium on renal function and cardiometabolic profile in patients with diabetes mellitus: a systematic review and meta-analysis of clinical trials.

PURPOSE: This systematic review and meta-analysis aimed to assess renal function and cardiometabolic biomarkers after treatment with beraprost sodium in patients with diabetes mellitus. METHODS: We systemically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to August 2020. Statistical heterogeneities were computed using Cochrane's Q test and I2 test. A fixed- or random-effects model was used to calculate the weighted mean difference (WMD) and corresponding 95% confidence intervals (CI). RESULTS: From 341citations, seven trials were included into our meta-analysis. Our findings demonstrated that beraprost sodium intake significantly decreased blood urea nitrogen (BUN) (WMD = -5.62, 95% CI [-8.49, -2.74], P < 0.001) and cystatin C (WMD = -0.57, 95% CI [-0.68, -0.46], P < 0.001). Beraprost sodium intake had no significant effect on fasting blood sugar (FBS), hemoglobin A1c (HbA1c), cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, systolic blood pressure (SBP), diastolic blood pressure (DBP), and creatinine (Cr) in patients with diabetes receiving beraprost sodium in comparison with the controls. CONCLUSION: Our meta-analysis revealed that beraprost sodium administration significantly decreased BUN and cystatin C levels in patients with diabetes. However, no significant effect was observed on the cardiometabolic profile.

Effects of Urtica dioica on Metabolic Profiles in Type 2 Diabetes: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Several studies have investigated the effect of Urtica dioica (UD) consumption on metabolic profiles in patients with type 2 diabetes mellitus (T2DM); however, the findings are inconsistent. This systematic review and meta-analysis of clinical trials were performed to summarize the evidence of the effects of UD consumption on metabolic profiles in patients with T2DM. METHODS: Eligible studies were retrieved from searches of PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar databases until December 2019. Cochran (Q) and I-square statistics were used to examine heterogeneity across included clinical trials. Data were pooled using a fixed-effect or random-effects model and expressed as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: Among 1485 citations, thirteen clinical trials were found to be eligible for the current metaanalysis. UD consumption significantly decreased levels of fasting blood glucose (FBG) (WMD = - 17.17 mg/dl, 95% CI: -26.60, -7.73, I2 = 93.2%), hemoglobin A1c (HbA1c) (WMD = -0.93, 95% CI: - 1.66, -0.17, I2 = 75.0%), C-reactive protein (CRP) (WMD = -1.09 mg/dl, 95% CI: -1.64, -0.53, I2 = 0.0%), triglycerides (WMD = -26.94 mg/dl, 95 % CI = [-52.07, -1.82], P = 0.03, I2 = 90.0%), systolic blood pressure (SBP) (WMD = -5.03 mmHg, 95% CI = -8.15, -1.91, I2 = 0.0%) in comparison to the control groups. UD consumption did not significantly change serum levels of insulin (WMD = 1.07 µU/ml, 95% CI: -1.59, 3.73, I2 = 63.5%), total-cholesterol (WMD = -6.39 mg/dl, 95% CI: -13.84, 1.05, I2 = 0.0%), LDL-cholesterol (LDL-C) (WMD = -1.30 mg/dl, 95% CI: -9.95, 7.35, I2 = 66.1%), HDL-cholesterol (HDL-C) (WMD = 6.95 mg/dl, 95% CI: -0.14, 14.03, I2 = 95.4%), body max index (BMI) (WMD = -0.16 kg/m2, 95% CI: -1.77, 1.44, I2 = 0.0%), and diastolic blood pressure (DBP) (WMD = -1.35 mmHg, 95% CI: -2.86, 0.17, I2= 0.0%) among patients with T2DM. CONCLUSION: UD consumption may result in an improvement in levels of FBS, HbA1c, CRP, triglycerides, and SBP, but did not affect levels of insulin, total-, LDL-, and HDL-cholesterol, BMI, and DBP in patients with T2DM.

The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of L-arginine supplements and their effect on maximal oxygen uptake (VO2 max) remained unclear. This systematic review aimed to investigate the effect of L-arginine supplementation (LAS) on VO2 max in healthy people. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane, Embase, ProQuest, and Ovid to identify all relevant literature investigating the effect of LAS on VO2 max. This meta-analysis was conducted via a random-effects model for the best estimation of desired outcomes and studies that meet the inclusion criteria were considered for the final analysis. RESULTS: The results of 11 randomized clinical trials indicated that LAS increased VO2 max compared to the control group. There was no significant heterogeneity in this meta-analysis. Subgroup analysis detected that arginine in the form of LAS significantly increased VO2 max compared to the other forms (weighted mean difference = 0.11 L min-1 , I2  = 0.0%, p for heterogeneity = 0.485). CONCLUSIONS: This meta-analysis indicated that supplementation with L-arginine could increase VO2 max in healthy people. Further studies are warranted to confirm this finding and to identify the underlying mechanisms.

The effects of glucagon-like peptide-1 receptor agonists on glycemic control and anthropometric profiles among diabetic patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

This study was undertaken to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs), mainly liraglutide and exenatide, on glycemic control and anthropometric profiles to see if they are effective in treating patients with non-alcoholic fatty liver disease (NAFLD) and type-2 diabetes mellitus (T2DM). We searched PubMed, Embase, Scopus, Web of Science (WOS), and Cochrane Library databases to identify all the randomized clinical trials (RCTs) up to August 23, 2020. Heterogeneity of the included studies was evaluated using Cochrane's Q test and the I2 statistic. Moreover, a random-effects model was used to pool the weighted mean differences (WMDs) and their 95% confidence intervals (CIs). Nine articles (12 studies) comprising a total of 780 participants aged 40-56 were finally selected. GLP-1RAs intake significantly reduced body mass index (BMI) (WMD -1.57, 95%CI; -2.74, -0.39), waist-circumference (WC) (WMD -4.14, 95%CI; -7.09, -1.19), body weight (WMD -4.20, 95%CI; -8.15, -0.25) among the body mass indices. Additionally, GLP-1RAs leads to lower postprandial plasma glucose (PPG) levels (WMD -25.73 mg/dl, 95%CI; -32.71, -18.75). We also found that GLP-1RAs intake has no significant effect on the waist-hip ratio (WHR) (WMD -0.01, 95%CI; -0.03, 0.02), fasting blood glucose (FBG) (WMD -2.12 mg/dl, 95%CI; -6.23, 1.96), hemoglobin A1c (HbA1c) (WMD -0.08%, 95%CI; -0.21, 0.04), and homeostatic model assessment for insulin resistance (HOMA-IR) levels (WMD -0.31, 95%CI; -0.69, 0.07). GLP-1RAs therapy showed a greater reduction in BMI, body weight, WC, and PPG, but not in WHR, HOMA-IR, FBG, and HbA1c compared with other therapies in patients with T2DM and NAFLD.

The Effects of Vitamin D Supplementation on Anthropometric and Biochemical Indices in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Background: Vitamin D was reported to be associated with non-alcoholic fatty liver disease (NAFLD). This systematic review and meta-analysis aimed to investigate the effects of the vitamin D supplementation on anthropometric and biochemical indices in patient with NAFLD. Methods: PubMed, Web of science, Scopus, and Embase databases were explored to identify all randomized controlled trial (RCT) investigating the effects of vitamin D supplementation on anthropometric and biochemical indices in patients with NAFLD. A random-effects model was used to pool weighted mean difference (WMD) and corresponding 95% confidence intervals (CIs). The statistical heterogeneity among the studies was assessed using I2 statistic (high ≥ 50%, low < 50%) and Cochran's Q-test. Results: Sixteen RCTs were included in this meta-analysis. The results identified that high-density lipoprotein-cholesterol (HDL-C) level significantly increased following vitamin D supplementation (P = 0.008). Vitamin D reduced body weight (P = 0.007), body mass index (P = 0.002), waist circumstance (WC) (P = 0.02), serum alanine transaminase (ALT) (P = 0.01), fasting blood sugar (FBS) (P = 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.004), and calcium (P = 0.01). No significant changes were found on body fat, triglyceride (TG), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and adiponectin following vitamin D supplementation. Conclusion: Vitamin D had significant effects on anthropometric and biochemical indices including HDL-C, body weight, BMI, WC, serum ALT, serum FBS, HOMA-IR, and calcium. Vitamin D supplementation can be considered as an effective strategy in management of patients with NAFLD. Systematic Review Registration: [website], identifier [registration number].

GLP-1 Receptor Agonist Effects on Lipid and Liver Profiles in Patients with Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis.

Aims: This meta-analysis of randomized placebo-controlled clinical trials assessed the effect of glucose-like peptide-1-receptor agonists (GLP-1RA) on the lipid profile and liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: Randomized placebo-controlled trials investigating GLP-1RA on the lipid profile and liver enzymes in patients with NAFLD were searched in PubMed-Medline, Scopus, Web of Science, and Google Scholar databases (from inception to January 2020). A random-effects model and a generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted. Weighted random-effects meta-regression was performed on potential confounders on lipid profile and liver enzyme concentrations. Results: 12 studies were identified (12 GLP-1RA arms; 677 subjects) that showed treatment with GLP-1RA reduced alanine transaminase (ALT) concentrations (WMD = -10.14, 95%CI = [-15.84, -0.44], P < 0.001), gamma-glutamyl transferase (GGT) (WMD = -11.53, 95%CI = [-15.21,-7.85], P < 0.001), and alaline phosphatase (ALP) (WMD = -8.29, 95%CI = [-11.34, -5.24], P < 0.001). Aspartate aminotransferase (AST) (WMD = -2.95, 95% CI = [-7.26, 1.37], P=0.18) was unchanged. GLP-1 therapy did not alter triglycerides (TC) (WMD = -7.07, 95%CI = [-17.51, 3.37], P=0.18), total cholesterol (TC) (WMD = -1.17 (-5.25, 2.91), P=0.57), high-density lipoprotein (HDL-C) (WMD = 0.97, 95%CI = [-1.63, 3.58], P=0.46), or low-density lipoprotein (LDL-C) (WMD = -1.67, 95%CI = [-10.08, 6.74], P=0.69) in comparison with controls. Conclusion: The results of this meta-analysis suggest that GLP-1RA treatment significantly reduces liver enzymes in patients with NAFLD, but the lipid profile is unaffected.

Effect of Liraglutide on Cardiometabolic Risk Profile in People with Coronary Artery Disease with or without Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Whether liraglutide use improves cardiometabolic risk factors in different subsets of subjects with coronary artery disease (CAD) remains unclear. In a systematic review and meta-analysis, we quantified the effects of liraglutide on cardiometabolic risk profile in subjects with CAD with or without type 2 diabetes mellitus (T2D). Methods: Online database searches were conducted in PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and Google Scholar from incept up to 15th January 2021. We identified randomized controlled trials (RCTs) assessing the effects of liraglutide compared to placebo on cardiometabolic risk profile. We used the random- or fixed-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Out of a total of 7,320 citations, six articles (seven RCTs) with 294 subjects with CAD (mean age, 61.21 years; 19% women) were included. Our findings presented as WMD and 95% CI showed a statistical significant decrease in hemoglobin A1c (HbA1c) [-0.36%; -0.47; -0.26, p < 0.001; I 2 = 0.0% (with 6 RCTs)], body mass index (BMI) [-0.61 kg/m2; -1.21; -0.01, p = 0.047; I 2 = 72.2% (with five RCTs)], and waist circumference [-2.41 cm; -3.47; -1.36, p < 0.001; I 2 = 0.0% (with three RCTs)]. Through a set of subgroup analyses, we found a significant reduction in BMI in CAD patients with T2D [WMD = -1.06; 95% CI, -1.42, -0.70, p < 0.001; I 2 = 0.0% (with three RCTs)] compared to CAD only patients [WMD = -0.08; 95% CI, -0.45, 0.29, p = 0.66; I 2 = 0.0% (with two RCTs)] in the liraglutide group compared with the placebo group. No significant changes in heart rate, blood pressure, and lipid profiles were observed. Conclusions: Among people with established CAD, liraglutide significantly improved HbA1c, BMI, and waist circumference values. The effect of liraglutide on BMI was more robust in individuals with T2D compared to those without.

Effects of Diacerein Intake on Cardiometabolic Profiles in Type 2 Diabetics: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: A systematic review and meta-analysis of clinical trials were undertaken to evaluate the effect of diacerein intake on cardiometabolic profiles in patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases such as PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched from inception to 31 July 2019. Statistical heterogeneity was evaluated using Cochran's Q test and I-square (I2) statistic. Data were pooled using random-effects models and weighted mean difference (WMD). RESULTS: From 1,733 citations, seven clinical trials were eligible for inclusion and meta-analysis. A significant reduction in hemoglobin A1c (HbA1c) (WMD -0.73; 95%CI -1.25 to -0.21; P= 0.006; I2= 72.2%) and body mass index (BMI) (WMD -0.55; 95%CI -1.03 to -0.07; P= 0.026; I2= 9.5%) was identified. However, no significant effect of diacerein intake was identified on fasting blood sugar (FBS) (WMD -9.00; 95%CI -22.57 to 4.57; P= 0.194; I2= 60.5%), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD 0.39; 95%CI -0.95 to 1.73; P= 0.569; I2= 2.2%), body weight (WMD - 0.54; 95%CI -1.10 to 0.02; P= 0.059), triglycerides (WMD -0.56; 95%CI -24.16 to 23.03; P= 0.963; I2= 0.0%), total-cholesterol (WMD -0.21; 95%CI -12.19 to 11.78; P= 0.973; I2= 0.0%), HDL-cholesterol (WMD -0.96; 95%CI -2.85 to 0.93; P= 0.321; I2= 0.0%), and LDL-cholesterol levels (WMD -0.09; 95%CI -8.43 to 8.25; P= 0.983; I2= 37.8%). CONCLUSION: Diacerein intake may reduce HbA1c and BMI; however, no evidence of the effect was observed for FBS, HOMA-IR, body weight, triglycerides, total cholesterol, HDL-cholesterol or LDLcholesterol.

The effectiveness of pistachio on glycemic control and insulin sensitivity in patients with type 2 diabetes, prediabetes and metabolic syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Pistachio nuts have been considered to improve dysglycemia. However, there are controversial results. This systematic review and meta-analysis carried out to evaluate the effects of pistachio nuts on glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM), prediabetes, and metabolic syndrome. METHODS: Medline/PubMed, ProQuest, Web of Knowledge, Scopus, Cochrane library, and ScienceDirect were systematically searched to find randomized controlled trials (RCTs). Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist was used to conduct the study. RESULTS: Six RCTs were included in the review. Treatment with pistachio nuts exerted a significant reduction in fasting blood glucose (FBG) level (OR = 1.7, 95% CI; 1.2-2.4, P = 0.002, I2 = 0.0%, P = 0.731) and homeostasis model assessment of insulin resistance (HOMA-IR) index (OR = 1.5, 95% CI; 1.0-2.4, P = 0.043, I2 = 0.0%, P = 0.617), but no significant improvement was observed in regard to hemoglobin A1c (HbA1c) level (OR = 1.4, 95% CI; 0.9-2.1 P = 0.089, I2 = 0.0%, P = 0.957) and fasting plasma insulin (FPI) level (OR = 1.3, 95% CI; 0.9-1.9, P = 0.133, I2 = 0.0%, P = 0.776). CONCLUSIONS: Pistachio nuts might cause a significant reduction in FBG and HOMA-IR, although HbA1c and FPI might not significantly improve in patients suffering from or at risk of T2DM.

The Therapeutic Role of Carotenoids in Diabetic Retinopathy: A Systematic Review.

BACKGROUND: Carotenoids are a large group of natural pigments that occur in many foods, fruits, and vegetables. Several studies have shown a number of biological properties of carotenoids, particularly beneficial impacts on cancer, metabolic, neurodegenerative, and cardiovascular diseases. However, recent evidence has shown that these compounds could prevent, delay, and ameliorate diabetic retinopathy (DR). The aim of current study was to review the therapeutic effects of carotenoids in the treatment of DR and discuss the molecular mechanisms that are behind these pharmacological activities. METHODS: Six online databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, ScienceDirect, and ProQuest) were searched until September 2019. The systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. RESULTS: A total of 25 studies were included after the final retrieval. A relationship was observed between carotenoids and management of DR. Findings also demonstrated that the underlying mechanism of beneficial effects of these compounds was antioxidant, anti-inflammatory, anti-angiogenic, and neuroprotective properties. CONCLUSION: Carotenoids potentially delay the initiation and prevent the progression of DR; however, ample preclinical studies are required to confirm their effect, and adequate clinical trials are needed to really understand how well these compounds influence DR among humans.