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Injectable therapies have been increasingly investigated to treat plantar fasciitis in randomized controlled trials (RCT) where normal saline injections are frequently used as placebo. The purpose was to quantify the effect of saline injections and compared against available minimal clinically important difference (MCID) criteria specific for plantar fasciitis to assess if changes were clinically meaningful.RCT including a placebo group (normal saline) and reporting changes in pain and functional outcomes in plantar fasciitis were identified through a search in MEDLINE, Embase, Web of Science, and Scopus to February 2022. PRISMA guidelines and a registered protocol (PROSPERO: CRD42020214035) were followed to conduct the study.Pooled analysis of 13 RCT (379 subjects) included for analysis revealed a significant improvement on pain (P .00001) and functional scores (P .00001) after normal saline injections. These changes exceeded the established MCID criteria.Normal saline injections in plantar fasciitis showed a therapeutic effect with statistically and clinically meaningful improvement when administered in the setting of an RCT for up to 12 months. The control of potential confounders influencing the effect of saline injections is required for future research.

Nonalcoholic fatty liver disease has become the most common liver disorder worldwide, reaching a prevalence of 60% and 24% in patients with chronic liver disease and the general population, respectively. Liver function is often assessed using standard liver tests such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Randomized controlled trials (RCTs) investigating the potential beneficial effects of coffee consumption on liver function are scarce and their results are inconclusive. Some clinical trials have shown a significant increase in adiponectin concentrations following coffee consumption; however, there are few studies in this field. Hence, the hypothesis of this meta-analysis of RCTs is that coffee consumption decreases blood markers of liver function and increases adiponectin concentrations. A systematic search was conducted in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta-analysis was performed using a random-effects model followed by sensitivity analysis. Meta-analysis of 14 RCTs, including a total of 897 subjects, showed that coffee consumption has no significant effect on alanine aminotransferase (weighted mean difference [WMD], -0.89 mg/mL; 95% CI, -2.90 to 1.12; P = .39), aspartate aminotransferase (WMD, -0.29 mg/mL; 95% CI, -1.25 to 0.66; P = .55), gamma-glutamyl transferase (WMD, .10 mg/mL; 95% CI, -3.94 to 4.15; P = .96), alkaline phosphatase (WMD, -4.60 mg/mL; 95% CI, -9.26 to 0.07; P = .05), and lactate dehydrogenase (WMD, -0.65 mg/mL; 95% CI, -10.80 to 9.49; P = .90). However, coffee administration significantly increased adiponectin concentrations (WMD, 1.19 mg/mL; 95% CI, 0.08-2.31; P = .04). The results of this meta-analysis of RCTs suggest that coffee consumption may improve liver dysfunction through the elevation of adiponectin levels; however, further clinical trials are needed to corroborate our findings.

It is well-recognized that hyperuricemia is a common abnormality among individuals with metabolic syndrome.The objective of this study was to determine whether hyperuricemia is associated with the metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) phenotypes.Men and women equal or greater than 18 years of age were enrolled in a cross-sectional study. Normal-weight subjects were allocated into the MONW or healthy normal-weight (HNW) groups; while obese individuals were divided into the MHO and metabolically unhealthy obese (MUO) subgroups. MONW phenotype was defined by body mass index (BMI)25.0 kg/mA total of 567 individuals were enrolled; of them, normal-weight subjects were allocated into the MONW (n = 101) and control (n = 72) groups, whereas obese individuals into the MHO (n = 61) and MUO (n = 333) groups. The multiple logistic regression analysis adjusted by age, gender, and body mass index revealed that hyperuricemia is significantly associated with MONW (OR = 5.14; 95% CI: 1.37-19.29) and MHO (OR = 0.34; 95% CI: 0.14-0.82) phenotypes.Results of our study showed that hyperuricemia is associated with both MONW and MHO phenotypes.

Background. Elevated serum low-density lipoproteins (LDL), the substrate for the formation of atherogenic oxidized LDLs (oxLDL), are a causal factor for atherosclerotic cardiovascular disease (ASCVD). Statins are well known to decrease LDL particle concentration and reduce ASCVD morbidity and mortality. Objective. To perform a meta-analysis of the effects of statins (i.e., type, dose, and duration of treatment) on serum levels of oxLDL and on immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels against oxLDL. Methods. PubMed, Scopus, Embase, and Web of Science were searched up to February 5th, 2021, for randomized controlled trials (RCT) evaluating the effect of statins on oxLDL and anti-oxLDL antibody levels. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. To evaluate the influence of each study on the overall effect size, a sensitivity analysis was performed using the leave-one-out method. Evaluation of the funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests was used to assess the presence of publication bias in the meta-analysis. Results. A total of 28 RCTs including 4019 subjects were finally included in the meta-analysis. The results indicated a significant decrease in circulating concentrations of oxLDL after treatment with statins (SMD: -2.150, 95% CI: -2.640, -1.697, p < 0.001 ). Subgroup analysis found no significant effect of the intensity of statin treatment or statin lipophilicity on the reduction of circulating concentrations of oxLDL. An additional meta-analysis of 3 trials showed that statins did not change the serum levels of IgM and IgG antibodies to oxLDL. Conclusion. Statin therapy decreases serum oxLDL concentrations but does not affect circulating levels of anti-oxLDL antibodies.

It has been reported that insulin resistance is related to cognitive decline. The triglycerides and glucose (TyG) index, is a reliable and inexpensive surrogate test for detecting insulin resistance.The goal of this study was to evaluate the association between the TyG index and the mild cognitive impairment (MCI) in older adults.A total of 135 individuals, men and women aged 60 to 90 years, were enrolled in a case and control study. Individuals with a diagnosis of MCI (n = 65) were allocated into the case group and compared with individuals without MCI (n = 70) in the control group. Alcohol intake, diabetes duration ≥5 years, diagnoses of cerebrovascular disease, brain injury, folic acid deficiency, dementia, moderate or severe CI, major depressive disorders, and thyroid disease were exclusion criteria.Individuals in the case group exhibited higher waist circumference (97.9 ± 13.9The TyG index is independently associated with the presence of MCI in older people.

The objective of this meta-analysis was to examine the impact of the GLP-1 RA on renal function parameters in randomized controlled trials.A systematic search was performed in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis.Data from 18 randomized controlled trials involving 12 192 subjects, showed that treatment with GLP-1 RA had no effect on serum creatinine levels (weighted mean difference [WMD]: 0.00 mg/mL, 95% confidence interval [CI]: -0.01, 0.01, P = .83, IResults of our meta-analysis revealed that GLP-1 RA treatment decreases urinary albumin excretion and albumin-to-creatinine ratio but it did not cause significant changes in creatinine levels and glomerular filtration rate.

Although magnesium intake is inversely associated with the risk of metabolic abnormalities, whether magnesium intake plays a role on metabolically healthy obese (MHO) phenotype has not been explored. Therefore, the purpose of this study was to determine whether the magnesium intake is associated with the MHO phenotype. Apparently, healthy women and men aged 20–65 years with obesity were enrolled in a cross-sectional study. Subjects were allocated into MHO (n=124) and metabolically unhealthy obese (MUO) (n=123) groups. MHO phenotype was defined by abdominal obesity (waist circumference ≥90 cm in men and ≥80 cm in women) and none, or not more than one of the following risk factors: triglyceride levels ≥150 mg/dL; high-density lipoprotein cholesterol (HDL-C) levels

Background: It has been suggested that hydroxychloroquine may have positive effects on LDL-C, HDL-C, and triglyceride levels; however, the hypolipidemic activities of this drug are still uncertain. Objective: The aim of this meta-analysis of randomized controlled trials was to explore the effect of hydroxychloroquine on circulating lipid concentrations. Methods: Randomized controlled trials examining the impact of hydroxychloroquine on lipid parameters were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave one-out method. Results: Meta-analysis showed that patients receiving hydroxychloroquine therapy significantly decreased total cholesterol (WMD: 0.18 mmol/L, 95% CI: -0.28, -0.08, I2 = 6%, p = 0.0004), LDL-C (WMD: -0.21 mmol/L, 95% CI: -0.36, -0.06, I2 = 75%, p = 0.006), triglycerides (WMD: -0.09 mmol/L, 95% CI: -0.15, -0.04, I2 = 22%, p = 0.001), and non-HDL-C (WMD: -0.28 mmol/L, 95% CI: -0.45, -0.12, I2 = 0%, p = 0.0009), and increased HDL-C concentrations (WMD: 0.03 mmol/L, 95% CI: 0.00, 0.06, I2 = 0%, p = 0.03). Conclusion: Our results suggest that hydroxychloroquine improves lipid parameters by reducing total cholesterol, LDL-C, triglycerides, non-HDL-C, and increasing HDL-C levels.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. It is associated with menstrual disturbances, hyperandrogenism, and polycystic ovaries. In addition to this, it results in altered anthropometric parameters, insulin resistance, and subsequently untoward cardio-metabolic sequelae. Therapeutic approaches that target weight loss and improve insulin sensitivity are used to address the metabolic complications in PCOS. Curcumin is a phytochemical which exhibits anti-inflammatory and anti-oxidant properties, and therefore, its use in PCOS has been a subject of substantial interest and research. The aim of this study was to synthesize the existing evidence on the effects of curcumin on glycaemic and lipid parameters in PCOS. We searched PubMed, Embase, Web of Science, Scopus, and ClinicalTrials databases from inception to June 07, 2021. Only randomized controlled trials (RCT) presenting sufficient data on glycemic and lipid parameters in patients with PCOS at baseline and the end of the follow-up period in each group were included. Meta-analysis of five RCTs showed a significant reduction on fasting glucose (WMD: − 3.68 mg/dL, 95% CI: − 5.11, − 2.25, p

PURPOSE Weight loss during post-bariatric surgery period has been linked to both reduced ASCVD mortality and overall mortality. Atherosclerosis causes arteries to lose their elasticity and become more stiff resulting in increased pulse wave velocity (PWV). It has been revealed that PWV favorably predicts subsequent ASCVDs. The goal of this systematic review and meta-analysis was to see how bariatric surgery affected PWV, an index of arterial stiffness. MATERIALS AND METHODS A systematic literature search in four databases was performed. Also, Cochrane guidelines were reviewed to determine bias possibility in the related studies. Comprehensive Meta-Analysis (CMA) V2 software is used to conduct the meta-analysis. Studies were evaluated regarding heterogeneity in design, populations under investigation, and treatment duration using random-effects model and the generic inverse variance weighting approach. A random-effect meta-regression approach was used to investigate the association with the estimated effect size. Evaluation of funnel plot, Egger's weighted regression, and Begg's rank correlation tests were utilized to estimate the presence of publication bias in the meta-analysis. RESULTS The results of meta-analysis on 13 trials including 1426 individuals demonstrated a remarkable decline of PWV after bariatric surgery (WMD: -0.652, 95% CI: -1.004, -0.301, p

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

The aim of this meta-analysis of randomized controlled trials was to evaluate the effect of hydroxychloroquine on glucose control. Randomized controlled trials examining the impact of hydroxychloroquine on glycemic markers were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave-one-out method. Meta-analysis revealed a significant reduction of fasting glucose (WMD: − 8.05 mg/dl; 95% CI: − 11.17, − 4.93; I2 = 75%; p ˂0.0001), 2-h postprandial glucose (WMD: − 15.52 mg/dl; 95% CI: − 20.61, − 10.42; I2 = 53%; p ˂0.00001), and glycated hemoglobin (HbA1c) values (WMD: − 0.19%, 95% CI: − 0.37, − 0.02; I2 = 94%; p = 0.03) after hydroxychloroquine treatment. Otherwise, meta-analysis showed no significant effect of hydroxychloroquine on insulin levels (WMD: 16.52 μUI/ml; 95% CI: − 16.35, 49.40; I2 = 90%; p = 0.32) and HOMA-β (WMD: − 14.62; 95% CI: − 45.84, 16.59; I2 = 0%; p = 0.36). The present meta-analysis revealed that treatment with hydroxychloroquine improves glucose control through the reduction of fasting glucose, 2-h postprandial glucose, and HbA1c values. Given that the effect of hydroxychloroquine on beta-cell function is based only on two clinical trials, it is not possible to draw definitive conclusions.

AIMS Previous studies have reported an elevation in adiponectin concentrations using glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy; however, this possible pleiotropic effect is still uncertain. Thus, the objective of this meta-analysis of randomized controlled trials was to assess the impact of GLP-1 RA on adiponectin levels. METHODS This systematic review and meta-analysis included randomized controlled trials investigating the effect of GLP-1 RA on circulating adiponectin concentrations. Studies from PubMed, Web of Science, Scopus, and Google Scholar databases were included. A random-effects model and a sensitivity analysis using the leave 1-out method were conducted. RESULTS A meta-analysis of 20 randomized controlled trials involving 1497 individuals demonstrated a significant increase in adiponectin levels after GLP-1 RA administration (weighted mean difference [WMD]: 0.59 μg/mL, 95% confidence interval [CI]: 0.10, 1.08, P = .02). Particularly, liraglutide had a significant effect on adiponectin (WMD: 0.55 μg/mL, 95% CI: 0.04, 1.06, P = .04), while exenatide did not affect these concentrations (WMD: 0.60 μg/mL, 95% CI: -0.23, 1.42, P = .16). CONCLUSION GLP-1 RA treatment is associated with an increase in adiponectin levels.

Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated.Report the results of the first years (2017-2019) of the Mexican FH registry.There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations.To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033).The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

Background: It has been reported that the consumption of antioxidant foods and beverages may benefit the development of cardiovascular risk factors. However, the impact of coffee consumption on some of these factors, such as homocysteine and leptin is controversial. Some clinical trials have suggested that coffee administration increases plasma total homocysteine levels, while others have found no significant changes in leptin concentrations. Objective: This study aimed to assess the effects of coffee supplementation on homocysteine and leptin concentrations in a meta-analysis of clinical trials. Method: PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar databases were searched from inception to September 29, 2021. A fixed-effects model and the generic inverse variance weighting method were used for meta-analysis. Results: The meta-analysis demonstrated that coffee administration significantly increases homocysteine levels (WMD: 0.55 μmol/L, 95% CI: 0.17, 0.93, p = 0.005, I2 = 0%) but has no significant changes in leptin concentrations (WMD: 1.34 ng/mL, 95% CI: -0.78, 3.45, p = 0.21, I2 = 0%). Additionally, the sensitivity analysis was robust for both homocysteine and leptin levels. Conclusion: The results of the present meta-analysis revealed that coffee supplementation raises serum homocysteine concentrations but has no effect on circulating leptin levels.

Objective: The aim of this meta-analysis of randomized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent. Methods: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched in order to find randomized controlled trials evaluating the effect of ursodeoxycholic acid on lipid profile. A random-effect model and the generic inverse variance weighting method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A random-effects meta-regression model was performed to explore the association between potential confounders and the estimated effect size on plasma lipid concentrations. Results: Meta-analysis of 20 treatment arms revealed a significant reduction of total cholesterol following ursodeoxycholic acid treatment (WMD: - 13.85 mg/dL, 95% CI: -21.45, - 6.25, p < 0.001). Nonetheless, LDL-C (WMD: -6.66 mg/dL, 95% CI: -13.99, 0.67, p = 0.075), triglycerides (WMD: - 1.42 mg/dL, 95% CI: -7.51, 4.67, p = 0.648) and HDL-C (WMD: -0.18 mg/dL, 95% CI: -5.23, 4.87, p = 0.944) were not found to be significantly altered by ursodeoxycholic acid administration. In the subgroup of patients with primary biliary cirrhosis, ursodeoxycholic acid reduced total cholesterol (WMD: - 29.86 mg/dL, 95% CI: -47.39, - 12.33, p = 0.001) and LDL-C (WMD: -37.27 mg/dL, 95% CI: -54.16, - 20.38, p < 0.001) concentrations without affecting TG and HDL-C. Conclusion: This meta-analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis.

Background: Some studies have revealed an improvement in glucose metabolism after proton-pump inhibitors (PPI) therapy; however, this evidence is inconclusive and limited. Objective: The study aimed to examine the effect of PPI on glucose and insulin metabolism in patients with type 2 diabetes through a systematic review and meta-analysis. Methods: Only randomized controlled trials evaluating the impact of PPI on glucose or insulin concentrations in type 2 diabetes were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A meta-analysis was conducted using a random-effects model and generic inverse variance method. Sensitivity analysis was performed using the leave-one-out method. Results: Meta-analysis revealed no significant effect of PPI intervention on fasting glucose (mean difference [MD] -11.42 [95% CI, -29.68 to 6.83], I2 = 80%, p = 0.22), fasting insulin (MD 1.51 [95% CI, -0.36 to 3.37], I2 = 32%, p = 0.11), HOMA-IR (MD -0.16 [-0.98 to 0.65], I2 = 0%, p = 0.70), HOMA-β (MD 19.97 [-21.59 to 61.52], I2 = 71%, p = 0.35), and HbA1c concentrations (MD -0.34 [-0.99 to 0.31], I2 = 89%, p = 0.30). Conclusion: The treatment with PPI, in the short term, had no significant effects on glucose and insulin metabolism in patients with type 2 diabetes.

Background: Lateral epicondylitis, or tennis elbow, is a painful degenerative disorder that commonly occurs in adults between 40 and 60 years of age. Normal saline (NS) injections have been used as placebo through a large number of randomized controlled trials (RCTs) focused on the treatment of lateral epicondylitis. Purpose: This meta-analysis of RCTs aimed to assess the therapeutic effect of NS injections on lateral epicondylitis symptoms and compare results with established minimal clinically important difference criteria. Study Design: Systematic review and meta-analysis. Methods: MEDLINE, Embase, Web of Science, and Scopus databases were searched for clinical trials reporting pain and joint function with the visual analog scale, Patient-Rated Tennis Elbow Evaluation, and Disabilities of the Arm, Shoulder and Hand in patients with lateral epicondylitis. The meta-analysis was conducted with a random effects model and generic inverse variance method. Heterogeneity was tested with the I2 statistic index. Results: A total of 15 RCTs included in this meta-analysis revealed a significant improvement in pain (mean difference, 3.61 cm [95% CI, 2.29-4.92 cm]; P < .00001; I2 = 88%; visual analog scale) and function (mean difference, 25.65 [95% CI, 13.30-37.99]; P < .0001; I2 = 82%; Patient-Rated Tennis Elbow Evaluation / Disabilities of the Arm, Shoulder and Hand) after NS injection (≥6 months). Conclusion: NS injections yielded a statistically significant and clinically meaningful improvement in pain and functional outcomes in patients with lateral epicondylitis. New research should focus on better methods to diminish the potential confounders that could lead to this effect because NS injections could mask the real effect of an active therapeutic intervention in RCT. Registration: CRD42019127547 (PROSPERO).

It has been suggested that the triglyceride and glucose (TyG) index is an early indicator for type 2 diabetes (T2D) in adults. Thus, the aim of this study was to evaluate whether the TyG index is useful in the screening of glucose disorders (GD) in apparently healthy children and adolescents. Eligible participants were apparently healthy children and adolescents. Individuals with new diagnosis of GD were allocated into the study groups with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and T2D. Participants with normal glucose tolerance (NGT) were the control group. In total, 1872 children and adolescents were enrolled and allocated into the study groups. Diagnosis of NGT, IFG, IGT, and T2D was established in 1541 (82.3%), 256 (13.7%), 66 (3.5%), and 9 (0.4%) children, respectively. In girls, the best cutoff points of the TyG index for identifying IFG, IGT, and T2D were 4.51 (sensitivity 59.8%, specificity 59.8%), 4.55 (sensitivity 63.0%, specificity 64.3%), and 4.63 (sensitivity 75.0%, specificity 74.6%), respectively; and in boys were 4.52 (sensitivity 62.8%, specificity 64.2%), 4.54 (sensitivity 71.8%, specificity 65.1%), and 4.82 (sensitivity 91.0%, specificity 990.6%), respectively.Conclusion: Our results suggest that the TyG index may be a useful tool for screening GD in healthy children and adolescents.What is Known:• Prevalence of prediabetes and type 2 diabetes is increasing worldwide among young adults and adolescents.• Elevated fasting glucose and triglyceride concentrations have been recognized as independent risk factors for type 2 diabetes.What is New:• The TyG index exhibited highest sensitivity and specificity to detect impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes.• The TyG index may be a useful tool for the screening of glucose disorders in apparently healthy children and adolescents.

Several studies have supported the usefulness of the triglycerides and glucose (TyG) index as a surrogate measure of insulin resistance; however, it has not been evaluated in insulin secretion. The aim of this study was to assess the association between the TyG index and insulin secretion in young adults with normal weight. Apparently healthy non-pregnant women and men, aged 18 to 23 years, were enrolled in a cross-sectional study. Overweight, obesity, pregnancy, smoking, alcohol consumption, diabetes, liver disease, renal disease, cardiovascular disease, and neoplasia were the exclusion criteria. Normal weight was defined by a body mass index (BMI)≥18.5

Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD.Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions.Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04).Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.

Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed.Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated.Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical.Both extracts exhibited higher inhibitory median concentration (ICBoth extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Plant extracts have been used to treat a wide range of human diseases. Curcumin, a bioactive polyphenol derived from Curcuma longa L., exhibits therapeutic effects against diabetes while only negligible adverse effects have been observed. Antioxidant and anti-inflammatory properties of curcumin are the main and well-recognized pharmacological effects that might explain its antidiabetic effects. Additionally, curcumin may regulate novel signaling molecules and enzymes involved in the pathophysiology of diabetes, including glucagon-like peptide-1, dipeptidyl peptidase-4, glucose transporters, alpha-glycosidase, alpha-amylase, and peroxisome proliferator-activated receptor gamma (PPARγ). Recent findings from in vitro and in vivo studies on novel signaling pathways involved in the potential beneficial effects of curcumin for the treatment of diabetes are discussed in this review.

OBJECTIVE We performed a systematic review and meta-analysis from randomized controlled trials to examine the efficacy and safety of avocado-soybean unsaponifiables (ASU) in patients with hip or knee osteoarthritis (OA). DATA SOURCES Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials. STUDY SELECTION Original studies were randomized placebo-controlled trials evaluating the effect of orally administered ASU on knee or hip OA symptoms using the Lequesne index, visual analog scale (VAS) and/or joint space width (JSW). DATA EXTRACTION Meta-analysis was conducted using a random-effects model and generic inverse variance method. Heterogeneity was tested using the I2 statistic index. DATA SYNTHESIS Avocado-soybean unsaponifiables therapy had a significant reduction on pain by VAS assessment (weighted mean difference [WMD]: -9.64 mm, 95% CI: -17.43, -1.84; P = .02; I2 = 92%). A subanalysis according to the type of OA showed that ASU significantly decreased both VAS and Lequesne index in knee OA (WMD: -17.36, 95% CI: -25.91, -8.82; P

Several classes of antidiabetic agents have been developed that achieve their hypoglycemic outcomes via various molecular mechanisms. Adipose tissue is a major metabolic and energy-storing tissue and plays an important role in many metabolic pathways, including insulin signaling and insulin sensitivity. Adipose tissue monitors and regulates whole body homeostasis via production and release of potent proteins, such as adipokine and adiponectin, into the circulation. Therefore, any agent that can modulate adipocyte metabolism can, in turn, affect metabolic and glucose homeostatic pathways. Antidiabetic drugs are not only recognized primarily as hypoglycemic agents but may also alter adipose tissue itself, as well as adipocyte-derived adipokine expression and secretion. In the current review, we present the major evidence concerning routinely used antidiabetic agents on adipocyte metabolism and adipokine expression.

The incidence of diabetes mellitus is growing rapidly. The exact pathophysiology of diabetes is unclear, but there is increasing evidence of the role of the inflammatory response in both developing diabetes as well as its complications. Resolvins are naturally occurring polyunsaturated fatty acids that are found in fish oil and sea food that have been shown to possess anti-inflammatory actions in several tissues including the kidneys. The pathways by which resolvins exert this anti-inflammatory effect are unclear. In this review we discuss the evidence showing that resolvins can suppress inflammatory responses via at least five molecular mechanisms through inhibition of the nucleotide-binding oligomerization domain protein 3 inflammasome, inhibition of nuclear factor κB molecular pathways, improvement of oxidative stress, modulation of nitric oxide synthesis/release and prevention of local and systemic leukocytosis. Complete understanding of these molecular pathways is important as this may lead to the development of new effective therapeutic strategies for diabetes and diabetic nephropathy.

Objectives The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia. Methods Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a randomized double-blind, placebo-controlled trial and randomly allocated to receive either resveratrol 100 mg/d or placebo (sucrose 0.5 g/d) for 2 mo. Smoking, alcohol intake, diabetes, acute or chronic renal or hepatic diseases, malignancy, cardiovascular disease, serum triacylglycerol levels ≥400 mg/dL, low-density lipoprotein cholesterol levels ≥190 mg/dL, and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria. Results Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and randomly allocated to the resveratrol (n = 35) or placebo groups (n = 36). At baseline, there were no significant differences between the study groups. After intervention period, individuals in the resveratrol group showed a significant decrease in total cholesterol (201.4 ± 34.4 versus 220.6 ± 37.4, P = 0.04) and triacylglycerol (133.4 ± 55.3 versus 166.7 ± 68.5, P = 0.04) concentrations compared with the placebo group, without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels. Conclusion The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia.

Background. Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. Objective. The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. Methods. PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used to assess the presence of publication bias. Results. Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001 ; I 2 : 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206 ; I 2 : 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004 ; I 2 : 0%). Conclusion. High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.

Curcumin has been shown to have beneficial effects on pathogenic factors involved in the development of atherosclerosis. The aim of this study was to assess the effects of curcumin phytosomes on atherosclerosis induced by high-fat diet in rabbits. A total of 16 adult male New Zealand white rabbits (1.8-2 kg) were fed with a diet containing 0.5% cholesterol for 4 weeks. The rabbits were randomly divided into four groups of four animals each. Group I orally received PBS for 4 weeks. Group II animals were treated with curcumin-phosphatidylcholine solid state dispersion (Meriva®, Indena, Italy) suspended in normal saline at doses equivalent to 100 mg/kg of curcuminoids per day p.o., for 4 weeks. Groups III and IV were treated with curcumin-phosphatidylserine solid state dispersion (Meriserin®, Indena, Italy) suspended in normal saline at doses equivalent to 10 and 100 mg/kg of curcuminoids, respectively, per day p.o., for 4 weeks. For atherosclerosis evaluation, histological examinations on aortic arch section were performed. Blood samples were obtained to determine lipid profile and high-sensitivity C-reactive protein (hs-CRP) levels. Curcumin-phosphatidylserine (100 mg/kg) therapy resulted in a significant reduction in grading of atherosclerotic plaque and intima/media thickness ratio (P 0.05) and decreased presence of inflammatory cells in the atherosclerotic lesions compared to the control group. However, no significant differences were observed between the curcumin-phospholipid preparations and the control group regarding lipid profile and hs-CRP levels. Results of the present study revealed an atheroprotective effect of curcumin-phosphatidylserine (100 mg/kg) solid dispersion as revealed by a reduction in the development of atherosclerotic lesions.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.

Non-alcoholic fatty liver disease is becoming in one of the most prevalent liver diseases that leads to liver transplantation. This health problem is a multisystem disease with a complex pathogenesis that involves liver, adipose tissue, gut, and muscle. Although several pharmacological agents have been investigated to prevent or treat non-alcoholic fatty liver disease, currently there is no effective treatment for the management of this chronic liver disease. Nonetheless, the use of natural products has emerged as a alternative therapeutic for the treatment of hepatic diseases, including non-alcoholic fatty liver disease, due to its anti-inflammatory, antioxidant, antidiabetic, insulin-sensitizing, antiobesity, hypolipidemic, and hepatoprotective properties. In the present review, we have discussed the evidence from experimental and clinical studies regarding the potential beneficial effects of plant-derived natural products (quercetin, resveratrol, berberine, pomegranate, curcumin, cinnamon, green tea, coffee, garlic, ginger, ginseng, and gingko biloba) for the treatment or prevention of non-alcoholic fatty liver disease.

Incretin hormones, including glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP), are gastrointestinal peptides secreted from enteroendocrine cells. These hormones play significant roles in many physiological processes via binding to G-protein coupled receptors (GPCRs) on different organs and tissues; one of them is the immunomodulatory effect on the immune system and its molecular components such as cytokines and chemokines. Anti-inflammatory effects of incretins and dependent molecules involving long-acting analogs and DPP4 inhibitors through regulation of T and B cell activation may attenuate autoimmune diseases caused by immune system disorders in mistakenly recognizing self as the foreign agent. In this review, we investigate incretin effects on the immune system response and the potential benefits of incretin-based therapy for treating autoimmune diseases.

The aim of this study was to evaluate the hypoglycemic and antioxidant potential of green tomato (Physalis ixocarpa Brot.) calyxes' extracts. Three methods were used to obtain the extracts: maceration (M), ultrasound-assisted (US), and infusion. Regarding in vitro hypoglycemic evaluation, glucose diffusion assay and enzymatic inhibitory action of α-amylase and α-glucosidase were performed. Whereas, for in vivo assessment an oral starch tolerance test (OSTT) was tested with aqueous extracts [infusion (40 mg/kg b. wt.), maceration (M) water (98 mg/kg b. wt.), and US water (82.24 mg/kg b. wt.)] on male Wistar rats. Additionally, in vitro antioxidant activity of P. ixocarpa calyxes' was evaluated through inhibition of scavenging radical assay and lipid peroxidation. Extracts decreased the glucose diffusion in a range of 18%-56% compared with the negative control. Additionally, extracts inhibited α-amylase (above 80%) and α-glucosidase enzymes (above 90%). All groups treated with P. ixocarpa calyxes' significantly reduced the glucose levels at 120 min (infusion = 13.3%, M Water = 12.7%, and US Water = 19.4%) in comparison with the negative control, and similar levels to acarbose at 120 min (13.1%). Finally, extracts showed IC50 values in a range of 2.5-6.6 µg/µl for radical scavenging, and 118-199 µg/µl for lipid oxidation. Our results show that P. ixocarpa calyxes' extracts induce hypoglycemia and antioxidant effects in vitro and in vivo. PRACTICAL APPLICATIONS: The green tomato is usually consumed in Mexico, the United States, and Central America. This fruit grows inside a calyx, which is considered an agro-food waste. However, some regions of Latin America have a traditional medicine purpose for diabetes affections. To the best of our knowledge, there are no published data that supports its hypoglycemic action. The information provided will be useful to nutraceutical applications that allow value-added products and sustainable green tomato production.

Aim Previous studies have found reduced concentrations of both leptin and resistin after glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment; however, the evidence in this field is inconclusive. Therefore, the aim of this meta-analysis of randomized controlled trials was to evaluate the effect of GLP-1 RA on both leptin and resistin levels. Methods The present systematic review and meta-analysis included randomized controlled trials investigating the effect of GLP-1 RA on leptin and resistin concentrations. For this, PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched. A random-effects model and a sensitivity analysis were performed for meta-analysis. Results Meta-analysis of 13 randomized controlled trials comprising 1,025 subjects indicated that administration of GLP-1 RA significantly decreases leptin (WMD: −4.85 ng/mL, 95% CI: −9.32, −0.38, p = 0.03) and resistin (WMD: −1.40 ng/mL, 95% CI: −2.78, −0.01, p = 0.05) serum levels. However, the effect size was sensitive to four studies for both leptin and resistin concentrations. Conclusion The results of this meta-analysis of randomized controlled trials suggest that GLP-1 RA therapy reduces both leptin and resistin levels.