The major molecular mechanisms mediating the renoprotective effects of SGLT2 inhibitors: An update

Abstract The incidence of diabetes mellitus, as well as its complications, is rapidly growing. Diabetic nephropathy is one of the most prevalent disorders induced by chronic uncontrolled hyperglycemia and is accompanied by a reduction in renal sufficiency with microstructural tissue damage in the kidneys. Many therapeutic protocols have been designed to address the treatment and prevention of diabetic nephropathy. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a newly introduced class of glucose-lowering agents that reduce blood glucose by inhibition of urinary glucose reabsorption in renal proximal tubules and so induce glycosuria. Also, these hypoglycemic agents may provide protective effects in different tissues such as cardiovascular, brain, and kidneys. In recent years, accumulating evidence has indicated that SGLT2i possess potent renal protective properties in the setting of diabetes. In the current study, we present the latest findings regarding the renoprotective effects of SGLT2 inhibition and discuss the molecular mechanisms involved

Effect of fenofibrate on plasma apolipoprotein C-III levels: a systematic review and meta-analysis of randomised placebo-controlled trials

OBJECTIVES: This meta-analysis of randomised placebo-controlled clinical trials aimed to assess the effect of fenofibrate on apolipoprotein C-III (apo C-III), a key regulator of triglyceride metabolism. ----- MATERIALS AND METHODS: Randomised placebo-controlled trials investigating the impact of fenofibrate treatment on apo C-III levels were searched in PubMed-Medline, Scopus, Web of Science and Google Scholar databases from inception to 18 August 2017. Quantitative data synthesis was determined by a random-effects model and generic inverse variance method. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate glycaemic parameter confounders. ----- RESULTS: Meta-analysis of 10 clinical trials involving 477 subjects showed fenofibrate therapy decreased apo C-III levels (weighted mean difference (WMD) -4.78 mg/dL, 95% CI -6.95 to -2.61, p200 mg/day (p=0.006), with no significant difference between the subgroups. ----- CONCLUSION: This meta-analysis found that fenofibrate therapy significantly decreases apo C-III levels, an effect evident with both short-term treatment and doses less than 200 mg/day

Inhibitory effects of Buddleja scordioides (salvilla) leaves on digestive enzymes and carbohydrate absorption in vivo

The effects of Buddleja scordioides (BsLI) leaf infusions on digestive enzymes and carbohydrate absorption were evaluated. The BsLI yield was 21.64 %. In addition, a chemical characterization was carried out identifying hydroxybenzoic acids, hydroxycinnamic acids, flavonols, flavanones and flavones. In vitro studies were performed to determine the inhibitory action of BsLI on lipase, α-amylase, and α-glucosidase. Then, in rats, oral starch tolerance tests (OSTT) were carried out using BsLI at a dose of 9.5 mg/kg body weight. Results showed moderate inhibition of lipase and α-glucosidase, but greater inhibition of α-amylase compared to positive controls. During the OSTT trial, the group receiving BsLI showed a significant reduction in glucose levels compared to the negative control group. Bioactive compounds, such as naringenin, luteolin, quercetin, and coumaric acid, were identified after BsLI administration. Furthermore, the consumption of BsLI was safe and showed antioxidant activity like Trolox. In conclusion, BsLI may have an enhanced effect on glucose metabolism by inhibiting carbohydrate absorption. DOI: https://doi.org/10.54167/tch.v17i2.122

The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women

Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD.Material and methods. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD.Results. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening.Conclusions. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH

Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: A systematic review and meta-analysis

Plasma lipoprotein(a) [Lp(a)] elevations are associated with increased cardiovascular risk. Coenzyme Q10 (CoQ10) is a member of the mitochondrial respiratory chain with a prominent role as a potent gene regulator. The Lp(a)-lowering efficacy of CoQ10 has been investigated in different clinical settings with contrasting results. A systematic literature search in Medline, SCOPUS, Web of Science and Google Scholar databases was conducted to identify controlled trials investigating the efficacy of CoQ10 supplementation on plasma Lp(a) levels. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in Lp(a) levels using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative confounders on plasma Lp(a) levels. Seven randomized controlled trials with a total of 409 subjects (206 in the CoQ10 arm and 203 in the control arm) met the eligibility criteria. Overall, CoQ10 supplementation was paralleled by a slight but significant reduction of plasma Lp(a) levels (WMD: -3.54 mg/dL, 95% CI: -5.50, -1.58; p<0.001), this effect being more robust in those trials with higher baseline Lp(a) levels (slope: -0.44; 95% CI: -0.80, -0.08; p=0.018). Reduction of plasma Lp(a) levels was consistent across different CoQ10 doses, with an inverse association between administered CoQ10 dose and Lp(a) lowering (slope: 0.04; 95% CI: 0.01, 0.07; p=0.004). Neither total cholesterol and cholesterol subfractions, nor triglyceride levels were affected by CoQ10 supplementation. In conclusion, CoQ10 supplementation, in the tested range of doses, reduces plasma Lp(a) concentrations, particularly in patients with Lp(a)≥ 30 mg/dL. Other lipid indices were not altered by CoQ10 supplementation

Impact of fibrate therapy on plasma plasminogen activator inhibitor-1: a systematic review and meta-analysis of randomized controlled trials

Objective: The aim of this systematic review was to perform a meta-analysis of randomized controlled trials (RCTs) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 (PAI-1).\ud \ud Methods: Scopus and MEDLINE databases were searched (up to October 15, 2014) to identify RCTs investigating whether fibrates lower plasma PAI-1 concentration or activity. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential moderators on the estimated effect sizes.\ud \ud Results: A total of 14 RCTs examining the effects of gemfibrozil (6 trials), bezafibrate (4 trials), and fenofibrate (5 trials) were included. Meta-analysis suggested that fibrate therapy did not significantly reduce plasma PAI-1 concentration (weighed mean difference [WMD]: −11.39 ng/mL, 95% CI: −26.64, 3.85, p = 0.143) or activity (WMD: 2.02 U/mL, 95% CI: −0.87, 4.90, p = 0.170). These results remained unchanged after subgroup analysis according to duration of treatment (<12 and ≥12 weeks) and type of fibrate administered (fenofibrate, bezafibrate or gemfibrozil). The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis.\ud \ud Conclusion: This meta-analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1

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

Abstract 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