Association of the triglycerides and glucose index and the homeostatic model assessment of insulin resistance with lipoprotein(a), apolipoprotein AI, and apolipoprotein B concentrations in children with normal-weight.

The aim of this study was to compare the association of the triglycerides and glucose (TyG) index and homeostatic model assessment of insulin resistance (HOMA-IR) with lipoprotein(a) (lp[a]), apolipoprotein AI (apoAI), and apoliprotein B (apoB) concentrations in children with normal-weight. Children with normal weight aged 6-10 years and Tanner 1 stage were included in a cross-sectional study. Underweight, overweight, obesity, smoking, alcohol intake, pregnancy, acute or chronic illnesses, and any kind of pharmacological treatment were exclusion criteria. According to the lp(a) levels, children were allocated into the groups with elevated concentrations and normal values. A total of 181 children with normal weight and an average age of 8.4 ± 1.4 years were enrolled in the study. The TyG index showed a positive correlation with lp(a) and apoB in the overall population (r = 0.161 and r = 0.351, respectively) and boys (r = 0.320 and r = 0.401, respectively), but only with apoB in the girls (r = 0.294); while the HOMA-IR had a positive correlation with lp(a) levels in the overall population (r = 0.213) and boys (r = 0.328). The linear regression analysis showed that the TyG index is associated with lp(a) and apoB in the overall population (B = 20.72; 95%CI 2.03-39.41 and B = 27.25; 95%CI 16.51-37.98, respectively) and boys (B = 40.19; 95%CI 14.50-65.7 and B = 29.60; 95%CI 15.03-44.17, respectively), but only with apoB in the girls (B = 24.22; 95%CI 7.90-40.53). The HOMA-IR is associated with lp(a) in the overall population (B = 5.37; 95%CI 1.74-9.00) and boys (B = 9.63; 95%CI 3.65-15.61).   Conclusion: The TyG index is associated with both lp(a) and apoB in children with normal-weight. What is Known: • The triglycerides and glucose index has been positively associated with an increased risk of cardiovascular disease in adults. What is New: • The triglycerides and glucose index is strongly associated with lipoprotein(a) and apolipoprotein B in children with normal-weight. • The triglycerides and glucose index may be a useful tool to identify cardiovascular risk in children with normal-weight.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials.

INTRODUCTION: Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis (OA). However, the effectiveness of PRP in advanced stages of the disease is not entirely clear. The purpose of this study was to evaluate whether the use of PRP would be as effective in studies with early-moderate knee OA patients compared to studies including patients with end-stage OA, based on the Kellgren-Lawrence classification. MATERIALS AND METHODS: A comprehensive search in MEDLINE, EMBASE, Scopus, and Web of Science databases was conducted to identify randomized controlled trials (RCTs) comparing the effect of PRP injections versus other intra-articular treatments on pain and functionality. A meta-analysis was conducted using a random-effects model and the generic inverse variance method. RESULTS: We included 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain [MD, - 1.05 (95% CI - 1.41 to - 0.68); I2 = 86%; P ≤ 0.00001] and function [SMD, - 1.00 (95% CI - 1.33, to - 0.66); I2 = 94%; P ≤ 0.00001], favoring PRP. Subanalysis for pain and functional improvement showed a significant pain relief in studies with 1-3 and 1-4 Kellgren-Lawrence OA stages and a significant functional improvement in studies with 1-2, 1-3 and 1-4 knee OA stages, favoring PRP. CONCLUSION: Our results indicate that including patients with advanced knee OA does not seem to affect the outcomes of clinical trials in which the effectiveness of the PRP in knee OA is assessed.

Effect of glucagon-like peptide-1 receptor agonists on renal function: A meta-analysis of randomized controlled trials.

AIMS: The objective of this meta-analysis was to examine the impact of the GLP-1 RA on renal function parameters in randomized controlled trials. METHODS: 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. RESULTS: 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, I2 = 0%) and glomerular filtration rate (WMD: 1.01 mL/min/1.73 m2 , 95% CI: -1.61, 3.63, P = .45, I2 = 75%). On the other hand, a significant reduction in urinary albumin excretion (WMD: -18.01 mg/day, 95% CI: -31.20, -4.82, P = .007, I2 = 23%) and albumin-to-creatinine ratio (WMD: -6.74 mg/g, 95% CI: -12.64, -0.85, P = .03, I2 = 68%) was detected after GLP-1 RA therapy. CONCLUSION: Results 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.

Serological follow up of positive SARS-CoV-2 cases.

OBJECTIVE: To describe the humoral response in a cohort with mild and asymptomatic SARS-CoV-2 infection previ-ously identified in a community-based serological survey. MATERIALS AND METHODS: This study was an observational follow up of 193 subjects previously identified with positive anti-SARS-CoV-2 antibodies invited for a second test 112 days after the first sampling. All completed a standardized electronic questionnaire. IgM/IgG antibodies were determined using a qualitative IgM/IgG chemiluminescent immunoassay. RESULTS: Among the 193 eligible subjects, a total of 174 (90%) attended the follow-up visit, and their serum samples were tested. Of the samples, 171 (98.3%) were still positive, and 3 (1.7%) were negative. Also, the cut-off index (COI) value of the immunoassay significantly increased from the first to the second test (P <0.001). CONCLUSIONS: Our findings support a sustained humoral response in individuals with mild and asymptomatic SARS-CoV-2 infection up to 112 days after a positive serologic baseline test, accompanied by increasing antibody titers.

Effect of sodium-glucose co-transporter 2 inhibitors on hepatic parameters: A systematic review and meta-analysis of randomized controlled trials.

Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we performed a meta-analysis of randomized controlled trials to evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hepatic parameters. PubMed, Web of Science, Scopus, and Google Scholar databases were searched to identify randomized controlled trials examining the effect of SGLT2 inhibitors on hepatic parameters. Meta-analysis was performed using a random-effects model and sensitivity analysis. Meta-analysis revealed that SGLT2 inhibitors therapy significantly lowered alanine aminotransferase (ALT) (WMD: -4.79 U/L, 95 % CI: -6.10, -3.47, I2 = 62 %, p < 0.00001), aspartate aminotransferase (AST) (WMD: -2.49 U/L, 95 % CI: -3.30, -1.68, I2 = 54 %, p < 0.00001), alkaline phosphatase (AP) (WMD: -1.13 U/L, 95 % CI: -2.03, -0.22, I2 = 23 %, p = 0.02), and gamma-glutamyl transferase (GGT) (WMD: -7.77 U/L, 95 % CI: -9.33, -6.21, I2 = 5 %, p < 0.00001). Additionally, SGLT2 inhibitors showed a significant increase in bilirubin levels (WMD: 0.64 U/L, 95 % CI: 0.27, 1.00, I2 = 53 %, p < 0.0006. Finally, no significant changes were found on albumin levels (WMD: 0.13 U/L, 95 % CI: -0.06, 0.32, I2 = 53 %, p < 0.0006) after SGLT2 inhibitors treatment. In conclusion, our results suggest that treatment with SGLT2 inhibitors exerts a beneficial effect on liver function tests through decreased ALT, AST, AP, and GGT concentrations.

Impact of glucagon-like peptide-1 receptor agonists on adiponectin concentrations: A meta-analysis of randomized controlled trials.

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.

Prevalence and associated characteristics of anti-SARS-CoV-2 antibodies in Mexico 5 months after pandemic arrival.

BACKGROUND: Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence. METHODS: We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student's t-test and the Mann-Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. RESULTS: Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1-6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9-5.5). CONCLUSIONS: There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.

Effect of hydroxychloroquine on glucose control in patients with and without diabetes: a systematic review and meta-analysis of randomized controlled clinical trials.

PURPOSE: The aim of this meta-analysis of randomized controlled trials was to evaluate the effect of hydroxychloroquine on glucose control. METHODS: 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. RESULTS: 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-ß (WMD: - 14.62; 95% CI: - 45.84, 16.59; I2 = 0%; p = 0.36). CONCLUSION: 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.

Beneficial Effects of Plant-Derived Natural Products on Non-alcoholic Fatty Liver Disease.

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.

Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: A systematic review and meta-analysis of 48 randomized controlled trials.

Previous studies have suggested additional beneficial effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors including the lipid-lowering effect; however, results on lipid profile are controversial. Thus, this meta-analysis aimed to determine the effect of SGLT2 inhibitors treatment on lipid levels in patients with type 2 diabetes. Randomized controlled trials assessing the impact of SGLT2 inhibitors on lipid parameters were searched in PubMed-MEDLINE, SCOPUS, Web of Science, and Google Scholar databases. Meta-analysis was conducted using a random-effects model and generic inverse variance method. Meta-analysis of 48 randomized controlled trials revealed that SGLT2 inhibitors therapy had a significant increase on total cholesterol (WMD: 0.09 mmol/L, 95 % CI: 0.05, 0.13, I2 = 79 %, p < 0.0001), LDL-cholesterol (WMD: 0.10 mmol/L, 95 % CI: 0.07, 0.12, I2 = 94 %, p < 0.00001), HDL-cholesterol (WMD: 0.06 mmol/L, 95 % CI: 0.05, 0.08, I2 = 99 %, p < 0.00001), and non-HDL-cholesterol (WMD: 0.09 mmol/L, 95 % CI: 0.06, 0.12, I2 = 96 %, p < 0.00001). Additionally, SGLT2 inhibitors administration showed a significant decrease in triglyceride levels (WMD: -0.10 mmol/L, 95 % CI: -0.13, -0.07, I2 = 96 %, p < 0.00001). Finally, no significant alteration was found on LDL/HDL ratio after SGLT2 inhibitors treatment (WMD: -0.01 mmol/L, 95 % CI: -0.05, 0.03, I2 = 99 %, p = 0.65). In conclusion, SGLT2 inhibitors significantly increase total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and HDL-cholesterol, and decrease triglyceride levels.

Effect of ursodeoxycholic acid on liver markers: A systematic review and meta-analysis of randomized placebo-controlled clinical trials.

AIM: The objective of this meta-analysis was to evaluate the effect of ursodeoxycholic acid (UDCA) therapy on serum liver function tests. METHODS: PubMed, Web of Science, Scopus and Google Scholar databases were searched to identify randomized placebo-controlled trials assessing the impact of UDCA on hepatic parameters. Meta-analysis was conducted using a random-effects model and sensitivity analysis through the leave-one-out method in the Review Manager statistical software version 5.3. RESULTS: After UDCA treatment, meta-analysis revealed a significant reduction of alanine aminotransferase (weighted mean difference [WMD]: -15.28 U/L, 95% confidence interval [CI]: -23.42, -7.15, P = 0.0002, I2 = 97%), aspartate aminotransferase (WMD: -16.13 U/L, 95% CI: -23.84, -8.42, P < 0.0001, I2 = 97%), gamma-glutamyl transferase (WMD: -23.29 U/L, 95% CI: -33.97, -12.61, P < 0.0001, I2 = 97%), alkaline phosphatase (WMD: -93.80 U/L, 95% CI: -126.36, -61.25, P < 0.0001, I2 = 95%) and bilirubin (WMD: -0.18 U/L, 95% CI: -0.35, -0.01, P = 0.04, I2 = 93%), but not significant changes in albumin levels (WMD: 0.10 U/L, 95% CI: -0.05, 0.24, P = 0.18, I2 = 80%). CONCLUSION: The results of the present meta-analysis suggest a hepatoprotective effect of UDCA by reducing serum liver parameters.

Diagnostic accuracy of the triglyceride-glucose index for gestational diabetes screening: a practical approach.

The oral glucose tolerance test (OGTT) remains as the gold standard to diagnose gestational diabetes mellitus (GDM); however, this test may be inconvenient and costly. Hence, other easy to perform and accurate diagnostic alternatives would be valuable for maternal care. The objective of the study was to assess the diagnostic performance of the TyG index to screen for GDM at 24-28 of pregnancy. A total of 140 pregnant women who received the one-step 2 h 75 g OGTT were included. Overall GDM prevalence was 27.1% according to IADSPG criteria. The mean TyG index value in the GDM group was significantly higher than the TyG index for the no GDM group (4.88 ± 0.70 versus 4.68 ± 0.19, p<.001). A sensitivity of 89% [95% CI 0.75-0.97] and a specificity of 50% [95% CI 0.39-0.60)], accompanied by a high negative predictive value of 93% was observed. No differences were found in maternal and neonatal outcomes irrespective of the TyG cutoff value for GDM. According to our results, the TyG index may be a highly sensitive and easy to perform screening test for GDM.

Acanthosis nigricans in middle-age adults: A highly prevalent and specific clinical sign of insulin resistance.

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials.

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.

Effect of ursodeoxycholic acid on glycemic markers: A systematic review and meta-analysis of clinical trials.

Ursodeoxycholic acid (UDCA) is widely used to treat liver diseases; however, its potential effect on metabolic parameters has been poorly investigated. Additionally, owing to divergent data, the objective of this meta-analysis was to evaluate the effect of UDCA on glycemic parameters in clinical trials. Clinical trials investigating the impact of UDCA treatment on glycemic markers were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 16, 2018). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters. Meta-analysis of seven studies comprising eight treatment arms revealed a significant reduction of fasting glucose levels following UDCA therapy (WMD: -3.30 mg/dL, 95% CI: -6.36, -0.24, p = 0.034; I2 = 28.95%). Also, meta-analysis of two treatment arms indicated a significant reduction of glycated hemoglobin (HbA1c) concentrations (WMD: -0.41% mg/dL, 95% CI: -0.81, -0.01, p = 0.042; I2 = 0%). Additionally, meta-analysis of four treatment arms also revealed a significant reduction in plasma insulin levels (WMD: -1.50 mg/dL, 95% CI: -2.81, -0.19, p = 0.025; I2 = 67.90%) but not significant effect HOMA-IR (WMD: -0.20 mg/dL, 95% CI: -0.42, 0.01, p = 0.057; I2 = 85.34%). Results of this meta-analysis showed that UDCA significantly reduces fasting plasma glucose, HbA1c, and insulin concentrations suggesting a positive impact on glucose homeostasis.

Effect of fibrates on glycemic parameters: A systematic review and meta-analysis of randomized placebo-controlled trials.

AIMS: The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of fibrates on glycemic parameters. MATERIALS AND METHODS: Only randomized placebo-controlled trials investigating the impact of fibrate treatment on glucose homeostasis markers were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 11, 2017). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters. RESULTS: This meta-analysis of data from 22 randomized placebo-controlled clinical trials involving a total of 11,402 subjects showed that fibrate therapy significantly decreased fasting plasma glucose (WMD: -0.28 mmol/L, 95% CI: -0.42, -0.14, p < 0.001), insulin levels (WMD: -3.87 pmol/L, 95% CI: -4.97, -2.78, p < 0.001) and insulin resistance (HOMA-IR, WMD: -1.09, 95% CI: -1.71, -0.47, p = 0.001), but with no effect on HbA1c (WMD: 0.01%, 95% CI: -0.18, 0.19, p = 0.955). All analyses were robust in the leave-one-out sensitivity analysis except for insulin levels that showed a non-significant result (WMD: -0.84 pmol/L, 95% CI: -6.36, 4.68, p = 0.766) following omission of one of the included trials. CONCLUSION: This meta-analysis has shown that fibrate treatment significantly decreases fasting plasma glucose, insulin levels, and HOMA-IR indicating additional clinical therapeutic benefits.

Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro.

BACKGROUND: Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy. METHODS: We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice. RESULTS: We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p < 0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase. CONCLUSION: T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment.

Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials.

Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.

Use of proteomic analysis tools to identify HCV-proteins down-regulated by acetylsalicylic acid.

Background and aim. Acetylsalicylic acid (ASA) has been shown to downregulate HCV expression; however, the involved mechanisms are unknown. We used proteomic analysis to compare protein expression profiles between human hepatocarcinoma cells (Huh7) and Huh7-HCV cells harboring expression of non-structural HCV proteins, to elucidate the mechanism(s) involved in ASA-mediated downregulation of HCV replication. Material and methods. Both cell lines were treated or untreated with 4 mM ASA and harvested at 0, 24, 48 and 72 h to isolate total proteins, which were resolved by two-dimensional gel electrophoresis (2DE) to separate them by isoelectric point (pI), followed by fractionation by molecular weight (MW). Gels were scanned and analyzed with PD-Quest software V8.0.1, and proteins were elucidated by the specific pI and MW using TAGIDENT software. Statistics analysis included the t-test. esults and Discussion. Different protein patterns among hepatocytes expressing HCV-proteins in ASA treated and untreated cells were found. Among proteins differentially expressed in Huh7-HCV cells, we found proteins related to cell proliferation (MTMR6, FAM22, HDGF and HCF-1) after 24 h of ASA treatment; and upregulation of angiostatin, PI4KA and STAT-1 after 48 h of treatment. Finally, at 72 h of ASA exposure, we identified overexpression of adenylsuccinate synthase, 2'-3'-di-deoxyadenosine, ubiquitin-protein-ligase E6A, adenylosuccinate-lyase and nibrin (NBN). Conclusion. We found that ASA induces different protein patterns in Huh7-HCV cells promoting activation of proteins involved in cell progression, repair of double strand breaks, proliferation, inhibition of apoptosis and growth stimulation at the same time that it decreased HCV expression.