Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis

Background and aimsSaroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia.MethodsElectronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)].ResultsFollowing 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: −123.67 to −19.66 mg/dl); P < 0.01; I² = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: −84.55–9.79 mg/dl; P = 0.12; I² = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: −44.13 to −5.09 mg/dl); P = 0.01; I² = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: −33.1–6.10 mg/dl; P = 0.18; I² = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04–0.21 mg/dl); P < 0.01; I² = 29% (low heterogeneity); high certainty of evidence].ConclusionThis meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.     

Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials

Background and aimsVitamin C has been used as an anti-oxidant in various diseases including viral illnesses like coronavirus disease (COVID-19).MethodsMeta-analysis of randomized controlled trials (RCT) investigating the role of vitamin C supplementation in COVID-19 was carried out.ResultsTotal 6 RCTs including n = 572 patients were included. Vitamin C treatment didn't reduce mortality (RR 0.73, 95% CI 0.42 to 1.27; I² = 0%; P = 0.27), ICU length of stay [SMD 0.29, 95% CI -0.05 to 0.63; I² = 0%; P = 0.09), hospital length of stay (SMD -0.23, 95% CI -1.04 to 0.58; I² = 92%; P = 0.57) and need for invasive mechanical ventilation (Risk Ratio 0.93, 95% CI 0.61 to 1.44; I² = 0%; P = 0.76). Further sub-group analysis based on severity of illness (severe vs. non-severe), route of administration (IV vs. oral) and dose (high vs. low) failed to show any observable benefits.ConclusionNo significant benefit noted with vitamin C administration in COVID-19. Well-designed RCTs with standardized control group needed on this aspect.     

Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD).MethodsElectronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events.ResultsData from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: ?5.41 to ?2.36); P < 0.01; I² = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: ?3.26 to ?3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to ?6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to ?1.23); P = 0.04; I² = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: ?8.45 to ?2.61); P < 0.01; I² = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: ?5.87 to ?1.23); P < 0.01; I² = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: ?14.64 to ?3.34); P = 0.002; I² = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to ?0.45); P = 0.002; I² = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76–7.06); P = 0.14; I² = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69–1.65); P = 0.77; I² = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33–4.22); P = 0.003; I² = 24%], diarrhea [RR 2.05 (95%CI: 1.17–3.60); P = 0.01; I² = 66%], nausea [RR 4.98 (95%CI: 3.23–7.67); P < 0.001; I² = 0%] and vomiting [RR 3.90 (95%CI: 1.75–8.68); P < 0.01; I² = 54%] were higher with semaglutide.ConclusionThis meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.     

Effects of probiotics supplementation on blood pressure: An umbrella meta-analysis of randomized controlled trials

AimsSeveral meta-analyses have revealed that probiotics could lower blood pressure (BP), but the findings were inconsistent. In this regard, an umbrella meta-analysis was carried out to provide a more accurate estimate of the overall impacts of probiotics supplementation on BP.Data synthesisWe searched the following international databases till November 2021: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. A random-effects model was applied to evaluate the effects of probiotics on BP. Sensitivity analysis was performed by using the leave-one-out method. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Pooled effect size of 14 meta-analyses with 15,494 participants indicated significant decreases in both systolic (Weighted mean difference (WMD) = ?1.96 mmHg; 95% confidence interval (CI): ?2.78, ?1.14, p < 0.001, and standardized mean difference (SMD) = ?2.62; 95% CI: ?4.96, ?0.28, p < 0.001) and diastolic BP (WMD = ?1.28 mmHg; 95% CI: ?1.76, ?0.79, p < 0.001, and SMD = ?0.60 mmHg; 95% CI: ?1.08, ?0.12, p = 0.014) following probiotics supplementation. Greater effects on SBP were revealed in trials with a mean age of >50 years and the duration of intervention ≤10 weeks. DBP was also more reduced in studies with a dosage of ≥10¹⁰ colony forming unit (CFU), and SBP was decreased in patients with hypertension or diabetes analyzing WMD.ConclusionThe present umbrella meta-analysis suggests probiotics supplementation to improve BP and claims that probiotics could be used as a complementary therapy for controlling high BP.Prospero IDCRD42022306560.     

Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledgeMethodsElectronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events.ResultsData from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12–24 weeks use, Hba1c [mean difference (MD) −0.13% (95% CI: 0.35 – 0.09%); P = 0.24; I² = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 – 7.88 mg/dl); P = 0.09; I² = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79–13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to −2.51 kg); P < 0.001; I² = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62–2.64); P = 0.58; I² = 59%] were comparable among groups.ConclusionRemogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin.     

Higher fasting fibroblast growth factor 21 was associated with a greater decline in postprandial blood pressure

BackgroundA fall in blood pressure (BP) following a meal is well known and is usually a transient phenomenon, due to appropriate cardiovascular adjustments. Older individuals and those with high BP experience a greater postprandial fall that can manifest as postprandial hypotension (PPH). Fibroblast growth factor 21 (FGF21) is positively associated with BP, and is known to increase after meal ingestion. We explored whether fasting FGF21 or its postprandial change would be associated with meal induced BP change, after accounting for several covariates.MethodsEighty-three Western Australian adults were studied. Supine resting BP was recorded and an oral glucose test was administered. Serial measurements of systolic BP (SBP) and diastolic BP (DBP) were then made in duplicate every 30 min up to 120 min. Fasting and 120 min blood samples were analysed for FGF21 and clinical chemistry. Multiple linear regression analyses of the incremental area under curve of postprandial SBP and DBP was conducted on 12 known determinants.ResultsThe final parsimonious model based on backward regression of postprandial SBP included fasting SBP, gender, fasting insulin and fasting FGF21 (β = ?0.009 (95% confidence interval (CI): 0.017, ?0.002, P = 0.015)). For postprandial DBP these included fasting DBP, gender, fasting glucose, fasting insulin and fasting FGF21 (β = ?0.005; 95% CI: 0.010, ?0.001, P = 0.021).ConclusionsA higher fasting FGF21, independent of glucose and insulin, was associated with a greater postprandial decline in SBP and in DBP.     

Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis

Background & aimsGlucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events.ResultsFrom initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12–24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: ?0.74 to ?0.59); P < 0.01; I² = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to ?18.94); P < 0.01; I² = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: ?46.26 to ?40.72); P < 0.01; I² = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50–14.46); P < 0.01; I² = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30–0.56); P < 0.01; I² = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05–2.18); P = 0.03; I² = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06–0.75); P = 0.03; I² = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11–1.83); P < 0.01; I² = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54–1.57); P = 0.76; I² = 0%] was significantly higher with dorzagliatin.ConclusionDorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.     

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis

Background & aimsPooled systematic analysis of safety and efficacy data of trelagliptin in type-2 diabetes (T2DM) is lacking. We undertook this meta-analysis to address this issue.MethodsElectronic databases were searched for RCTs involving people with T2DM receiving trelagliptin in study arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in pre and post-meal glucose levels, glycaemic targets, lipid parameters and adverse events.ResultsFrom initially screened 63 articles, data from 6 RCTs involving 981 patients was analysed [3 in active control group (ACG) defined as having alogliptin, sitagliptin, linagliptin, teneligliptin, anagliptin or vildagliptin as active comparator; 2 in passive control group (PCG) defined as having placebo as controls; 1 study had both ACG and PCG]. HbA1c reduction by trelagliptin was comparable to ACG [MD 0.06% (95% CI: ?0.03 – 0.16); P = 0.20; I² = 0%], but superior to PCG [MD -0.54% (95% CI: ?0.64 to ?0.44); P < 0.01; I² = 22%]. Fasting blood glucose lowering with trelagliptin was inferior to ACG [MD +6.98 mg/dl (95%CI: 2.55–11.42); P = 0.002; I² = 0%], but superior to PCG [MD -6.11 mg/dl (95%CI: ?12.00 to ?0.23); P = 0.04; I² = 54%]. Glycated albumin lowering was similar to ACG [MD 0.03% (95%CI: ?0.47 – 0.53); P = 0.92; I² = 0%], but superior to PCG [MD -2.31% (95% CI: ?2.86 to ?1.76); P < 0.01; I² = 0%]. Treatment-emergent adverse events [Risk ratio (RR) 1.18 (95%CI:0.63–2.21); P = 0.59; I² = 19%] and severe adverse events [RR 1.75 (95%CI: 0.90–3.40); P = 0.10; I² = 0%] were comparable among groups.ConclusionOnce weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM.     

Effects of immediate or early oral feeding on acute pancreatitis: A systematic review and meta-analysis

BackgroundThe timing of oral refeeding can affect length of stay (LOS) and recovery of acute pancreatitis (AP). However, the optimal timing for oral refeeding is still controversial for AP. This meta-analysis investigated the effects of immediate or early versus delayed oral feeding on mild and moderate AP, regardless of improvement in clinical signs or laboratory indicators.MethodsThis systematic review and meta-analysis of randomized controlled trials (RCTs) based on data from Embase, Cochrane Library, PubMed, Web of science, and CBM before August 2021. Two researchers independently used Stata16 to extract and analyse study data. Random effect model was performed for meta-analysis to calculate the risk ratio (RR) and standardized mean difference (SMD).Results8 RCTs were selected, including 748 patients with mild to moderate AP. Patients in IOR (Immediate or early Oral Refeeding) group had less costs [SMD -0.83, 95%CI (?1.17, ?0.5), P < 0.001] and shorter LOS [SMD -1.01, 95%CI (?1.17, ?0.85), P < 0.001] than the DOR (Delayed Oral Refeeding) group patients. However, there was no difference in mortality [RR 0.54, 95%CI (0.11, 2.62), P = 0.44], pain relapse rate [RR 0.58, 95%CI (0.25, 1.35), P = 0.27], feeding intolerance rate [RR 0.61, 95%CI (0.28, 1.3), P = 0.2], AP progression rate [RR 0.21, 95%CI (0.04, 1.07), P = 0.06] and overall complications rate [RR 0.41, 95%CI (0.17, 1.01), P = 0.05] between the IOR and DOR groups.ConclusionsLimited data suggest that IOR could reduce LOS and costs without increasing adverse events in mild to moderate AP.     

Relationship between serum uric acid levels and different types of atrial fibrillation: An updated meta-analysis

AimIncreasing evidence supports the hypothesis that high serum uric acid (SUA) levels are related to atrial fibrillation (AF). However, the incidence of AF in patients with hyperuricemia and SUA levels in different types of AF is not entirely clear. This meta-analysis was designed to evaluate the relationship between SUA and incidence of AF, and the variation in SUA levels in different types of AF.Data synthesisRelevant reports were searched for in Embase, PubMed and the Cochrane Library. A fixed-effects model combining relative risk (RR) and the corresponding 95% confidence interval (95% CI) was used to evaluate the correlation between SUA and AF. The standardized mean differences (SMDs) of SUA values were calculated using a random-effects model to evaluate the differences in SUA levels among different types of AF.A total of 31 studies with 504,958 participants were included in this research. The results from 8 cohort studies showed that high SUA levels significantly increased the incidence of AF [RR (95% CI): 1.92 (1.68–2.20); P < 0.01]. The results from 29 studies revealed that SUA levels elevated in patients with AF [SMD (95% CI): 0.55 (0.43–0.66); P < 0.001]. Meanwhile, SUA levels in new-onset AF [SMD (95%CI): 0.24 (0.10–0.38); P = 0.001], paroxysmal AF [SMD (95%CI): 0.52 (0.33–0.72); P < 0.001] and persistent AF [SMD (95%CI): 1.23 (0.98–1.48); P < 0.001] were significantly higher than that in patients without AF.ConclusionsHigh SUA levels had an obvious correlation with the occurrence rate of AF. In addition, SUA levels were significantly different among patients with new-onset, paroxysmal and persistent AF.     

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis

Background and aimsNo meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events.ResultsFrom initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11–0.17); P = 0.65; I² = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66–7.60); P = 0.64; I² = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55–23.62); P = 0.56; I² = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60–6.09); P = 0.79; I² = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72–6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78–1.47); P = 0.67; I² = 0%] and severe AEs [RR 1.05(95%CI: 0.42–2.65); P = 0.91; I² = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08–6.17); P = 0.03; I² = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78–1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19–0.33); P = 0.60; I² = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema.ConclusionThe current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.     

Association of adherence to the dietary approach to stop hypertension and Mediterranean diets with blood pressure in a non-hypertensive population: Results from Isfahan Salt Study (ISS)

Background and aimsHypertension is among the major risk factors for cardiovascular events in the Iranian population. This cross-sectional study was designed to examine the association of adherence to the dietary approaches to stop hypertension (DASH) and Mediterranean (MED) dietary patterns with the distribution of blood pressure and pre-hypertension prevalence.Methods and resultsThis cross-sectional study was carried out in 1363 non-hypertensive adults. Adherence to the DASH and MED diets was calculated using a semi-quantitative food frequency questionnaire (FFQ). Hypertension was measured by the standard method. Multiple logistic regression was applied to obtain the odds ratio of pre-hypertension in the tertiles of MED and DASH dietary patterns. Compared to the lowest, participants with the highest adherence to the DASH dietary pattern had significantly lower systolic blood pressure (SBP) (111.3 ± 11.8 vs. 112.8 ± 12.5; P = 0.010) and diastolic blood pressure (DBP) (70.7 ± 9.2 vs. 71.8 ± 9.8; 0.042). There was no significant difference in the mean SBP and DBP among the participants across tertiles of MED or diet adherence. Higher scores of the DASH and MED diets were inversely associated with lower SBP after adjustment for all potential confounders (OR = ?0.04, 95% CI = ?0.29, ?0.01, P = 0.039) and (OR = ?0.04, 95% CI = ?0.72, ?0.02, P = 0.044), respectively. Also, DASH and MED dietary patterns was associated with reduced OR of pre-hypertension occurrence by 13% (OR: 0.87; 95% CI: 0.70–0.98; P for trend = 0.042) and 16% ([OR: 0.84; 95% CI: 0.69–0.97; P trend = 0.035), respectively.ConclusionAdherence to the DASH and MED diets was inversely associated with the odds for pre-hypertension and SBP.     

A machine learning approach identifies modulators of heart failure hospitalization prevention among patients with type 2 diabetes: A revisit to the ACCORD trial

BackgroundTo examine patient characteristics that may modulate the heterogeneous treatment effect of intensive systolic blood pressure control (SBP) and intensive glycemic control on incident heart failure (HF) risk in people with type 2 diabetes.MethodsWe analyzed 10,251 participants from the ACCORD glucose trial, and 4733 from the SBP sub-trial separately. We applied a robust machine-learning (ML) algorithm, namely the causal forest/causal tree analysis, to each trial to identify participants' characteristics that modulate the effectiveness of each trial intervention.ResultsDiastolic blood pressure (DBP) was found to interact with intensive glycemic control and impact outcomes. An increased HF risk associated with intensive glycemic control (absolute risk change (ARC): 2.28 %, 95 % confidence interval (CI): 0.69 % to 3.90 %; relative risk (RR):1.57, 95 % CI: 1.15 to 2.20; P < 0.05) was observed in individuals with baseline DBP at the lowest tertile (45–69 mmHg), while no changes in HF risk associated with intensive glycemic control were observed in individuals with baseline DBP at the middle (70–79 mmHg) and the highest tertiles (80–100 mmHg). Liver function was identified as a modulator of intensive BP control, and baseline Alanine transaminase (ALT) level was a sensitive marker for the modulating effect. Only individuals with baseline ALT at the lowest tertile (8–19 mg/dl) benefited from the intensive BP control for HF prevention (ARC: ?1.95 %, 95 % CI: ?4.06 % to 0.11 %; RR:0.62. 95 % CI: 0.27 to 0.94; P < 0.05).ConclusionsOur study is the first to observe and quantify the potential synergistic harmful effect when low DBP was combined with an intensive blood glucose intervention. Recognizing these may help clinicians develop a more precise approach to such treatments, thus increasing the efficiency and outcomes of diabetes treatments.     

Effect of saffron supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials

Background and aimsPossible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes.MethodsAn electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size.ResultsEight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: −0.18; 95% CI: −0.34, −0.02; I² = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: −0.14; 95% CI: −0.36, 0.09; I² = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: −0.18, 0.46; I² = 42.9%) compared to placebo.ConclusionsSaffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.     

Individual or familial diabetes in relation to eight cardiovascular diseases: A two-sample Mendelian randomization study

Background and aimsDiabetes is associated with increased risk of certain cardiovascular diseases, yet the causality remains to be determined. Meanwhile, given that first-degree relatives share 50% of genes, the effect of familial diabetes is also worthy of attention. Therefore, we sought to investigate the causal relations of individual or familial diabetes with eight cardiovascular diseases, including myocardial infarction, hypertension, atrial fibrillation, heart failure, cardiac death, pulmonary embolism, transient ischemic attack, and ischemic stroke.Methods and resultsApplying two-sample Mendelian randomization, we selected instruments for genetic predisposition to individual or familial diabetes based on published genome-wide association studies. The primary analyses were conducted using the random-effects inverse-variance weighted method. We found that genetically predicted individual diabetes was causally associated with higher risks of myocardial infarction (odd ratio [OR] = 1.09; 95% confidence interval [CI]: 1.05–1.13; P < 0.0001), hypertension (OR = 1.08; 95% CI: 1.03–1.13; P = 0.0006), and ischemic stroke (OR = 1.10; 95% CI: 1.05–1.15; P < 0.0001). Genetically predicted paternal diabetes could increase the risk of ischemic stroke (OR = 1.16; 95% CI: 1.04–1.30; P = 0.0061). Genetically predicted maternal diabetes could increase the risk of myocardial infarction (OR = 1.18; 95% CI: 1.09–1.29; P = 0.0001). Genetically predicted siblings’ diabetes was causally associated with higher risks of myocardial infarction (OR = 1.17; 95% CI: 1.08–1.27; P = 0.0001) and hypertension (OR = 1.19; 95% CI: 1.06–1.34; P = 0.0036). No significant differences were observed in other outcomes.ConclusionThis study supports causal effects of not only individual but also familial diabetes on the development of cardiovascular diseases, which will help realize the potential effect of family history in the prevention of cardiovascular diseases.     

Comparison of laboratory parameters in mild vs. severe cases and died vs. survived patients with COVID-19: systematic review and meta-analysis

BackgroundThis study aimed to summarize the available data on the association between the severity of (COVID-19) and routine blood indicators, inflammatory, biochemical parameters and coagulation parameter.MethodsA literature search was conducted of PubMed, EMBASE, and Web of Sciences, CNKI, WanFang database providing relevant data. Random-effects meta-analysis was used to pool effect sizes.ResultsIn patients with severe symptoms, interleukin-6, [IL-6; standardized mean difference (SMD) =1.15, 95% confidence interval (95% CI): 1.01, 1.29, P<0.001, n=1,121], interleukin-10 (IL-10; SMD =0.92, 95% CI: 0.75, 1.08, P<0.001, n=782), interleukin-4 (IL-4; SMD =0.2, 95% CI: 0.01, 0.39, P=0.04, n=500), procalcitonin (PCT; SMD =1.16, 95% CI: 0.99, 1.33, P<0.001, n=734), C-reactive protein (CRP; SMD =1.42, 95% CI: 1.27, 1.57, P<0.001, n=1,286), serum amyloid A (SAA; SMD =2.82, 95% CI: 2.53, 3.11, P<0.001, n=502) neutrophil count (SMD =0.63, 95% CI: 0.44, 0.82, P<0.001, n=558), alanine aminotransferase (ALT; SMD =2.72, 95% CI: 2.43, 3.02, P<0.001, n=538), aspartate aminotransferase (AST; SMD =2.75, 95% CI: 2.37, 3.12, P<0.001, n=313), lactate dehydrogenase (LDH; SMD =4.01, 95% CI: 3.79, 4.24, P<0.001, n=1,055), creatine kinase (CK; SMD =2.62, 95% CI: 2.2, 3.03, P<0.001, n=230;), CK-MB isoenzyme (CK-MB; SMD =3.07, 95% CI: 2.81, 3.34, P<0.001, n=600, activated partial thromboplastin time (APTT; SMD =0.63, 95% CI: 0.39, 0.87, P<0.001, n=351), and prothrombin time (P-T; SMD =1.83, 95% CI: 1.55, 2.11, P<0.001, n=351) were significantly higher than in patients with mild symptoms. On the contrary, lymphocyte count (SMD =−1.04, 95% CI: −1.21, −0.86, P<0.001, n=805) platelets (SMD =−1.47, 95% CI: −1.7, −1.24, P<0.001, n=653), monocyte count (SMD =−0.56, 95% CI: −0.8, −0.32, P<0.001, n=403), and albumin (SMD =−2.95, 95% CI: −3.21, −2.7, P<0.001, n=637) was significantly lower in patients with severe symptoms than in patients with mild symptoms. IL-6 (SMD =2.62, 95% CI: 2.15, 3.09, P<0.001, n=185), PCT (SMD =0.2, 95% CI: 0.16, 0.23, P<0.001, n=156), creatinine (SMD =2.29, 95% CI: 1.87, 2.7, P<0.001, n=213), and neutrophil counts (SMD =2.77, 95% CI: 2.38, 3.16, P<0.001, n=260) in patients with COVID-19 in the death group were significantly higher than that in patients in the survival group, while the lymphocyte count was significantly lower.ConclusionsIn summary, current evidence show that those laboratory indicators are associated with the severity of COVID-19 and thus could be used as prognostic risk stratification of patients with COVID-19.     

Visit‐to‐visit variability of blood pressure and risk of macrovascular and microvascular complications in patients with type 2 diabetes: A Chinese primary‐care cohort study

BackgroundWe evaluated the effects of visit‐to‐visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on macrovascular and microvascular complications among patients with type 2 diabetes.MethodsA total of 11 043 patients with type 2 diabetes from primary healthcare institutions between January 2010 and June 2020 were included. The visit‐to‐visit blood pressure variability was calculated using three metrics: SD, coefficient of variation (CV), and average real variability (ARV), obtained over a 12‐month measurement period. The associations of visit‐to‐visit blood pressure variability with macrovascular and microvascular complications were evaluated using multivariate‐adjusted Cox proportional hazards models, and hazard ratio (HR) with 95% confidence interval (CI) were reported.ResultsThere were 330 macrovascular events and 542 microvascular events. Compared to those for participants with the lowest quartile of SD of SBP and DBP, increased risks were observed in patients with the highest quartile of SD of SBP and DBP for macrovascular complications (SD‐SBP: HR = 1.78, 95% CI: 1.24–2.57; SD‐DBP: HR = 2.20, 95% CI: 1.50–3.25) and microvascular complications (SD‐SBP: HR = 1.85, 95% CI: 1.39–2.46; SD‐DBP: HR = 1.82, 95% CI: 1.36–2.44). CV and ARV of SBP and DBP also had statistically significant associations with macrovascular and microvascular complications. The optimal variability of blood pressure target was SD of SBP <6.45 mm Hg and SD of DBP <4.81 mm Hg.ConclusionsVisit‐to‐visit blood pressure variability may be a potential predictor for macrovascular and microvascular complications in patients with type 2 diabetes.     

Uric acid and blood pressure in NHANES dated from 2009 to 2018: A cross-sectional research

Background and aimThis study aimed to explore the association between uric acid (UA) and blood pressure (BP), included systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP).Methods and resultsA cross-sectional study with 22,478 individuals aged from 12 to 80 years (11,443 males and 11,035 females) from the National Health and Nutrition Examination Survey (NHANES) was performed. Multiple linear regression analysis was applied to explore the relationship between UA and BP, Stratified analysis and interaction were performed based on gender, race, age, body mass index (BMI), and alcohol consumption. Significantly positively associations were presented in SBP(β, 0.84 [95% CI, 0.67, 1.00]), DBP(β, 0.23 [95% CI, 0.11, 0.36]), and MAP (β, 0.43 [95% CI, 0.31, 0.55]). The associations were much more stronger between UA and SBP in females (β, 1.04 [95% CI, 0.78, 1.30], p for interaction 0.0003), black group (β, 1.17 [95% CI, 0.77, 1.56], p for interaction 0.0296), age (≥45) group (β, 1.03 [95% CI, 0.68, 1.39], p for interaction <0.0001) and drinking group (β, 0.98 [95% CI, 0.75, 1.21], p for interaction <0.0001). The significant interactions were found between UA and DBP in gender and alcohol consumption (all p for interaction <0.05). In terms of MAP, the significant interactions were found in race, age, and alcohol consumption (all p for interaction <0.05).ConclusionsA significantly positively association was found between UA and BP, including SBP, DBP, and MAP.     

Effect of DASH diet on oxidative stress parameters: A systematic review and meta-analysis of randomized clinical trials

Background and aimsOxidative stress (OS) is one of the main risk factors for several chronic diseases. The Dietary Approaches to Stop Hypertension (DASH) contain many antioxidants and may contribute to managing OS.ObjectiveTo perform a systematic review and meta-analysis to examine the impacts of the DASH diet on OS parameters.MethodsA comprehensive electronic search in MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials was performed through September 2020 to find related studies evaluating the impact of the DASH diet on OS parameters. Standardized mean differences were pooled using random-effects meta-analysis.ResultsEight studies with a total of 317 subjects met our inclusion criteria. Four studies included in meta-analysis model with 200 participants (100 in treatment and 100 in control group). The DASH diet was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD: −0.53; 95% CI: −0.89, −0.16; I² = 42.1%), and a significant increase in glutathione (GSH) (SMD: 0.83; 95% CI: 0.36, 1.03; I² = 42.1%). Meta-analysis found no statistically significant effect of DASH diet on nitric oxide (NO) (SMD: −1.40; 95% CI: −0.12, 1.93; I² = 92.6%) or total antioxidant capacity (TAC) levels (SMD: 0.95; 95% CI: −0.10, 1.99; I² = 87.6%).ConclusionOur results demonstrated that a DASH diet could significantly increase GSH and decrease MDA levels. Furthermore, there is a trend to improve TAC, NO, and f2-isoprostanes by the adherence to the DASH diet. However, long-term, large sample size and well-designed randomized clinical trials are still needed to draw concrete conclusions about DASH diet’s effects on OS parameters.     

Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown.PurposeWe conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD.MethodsElectronic databases (MEDLINE and Cochrane CENTRAL) were searched from their inception until May 2021 for observational studies and randomized controlled trials (RCTs) that assessed the efficacy of statins for the treatment of NAFLD and its development. Studies were included irrespective of the dosage or duration, and their risk of bias was assessed. The outcomes of interest for our study were the effect of statins on liver histology (steatosis, fibrosis and necroinflammation, NAFLD activity score [NAS]) and liver enzymes (Alanine transaminase [ALT], Aspartate transaminase [AST], and Gamma-glutamyl transferase [GGT] levels). To pool continuous outcomes, a random-effects model was used to derive weighted mean difference (WMD) or standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs). Generic inverse variance was then used for different measurement units reported by the studies. For studies investigating the effects of statins on the development of NAFLD, generic inverse variance along with random effects model was used to derive odds ratio (ORs) and its corresponding 95% confidence interval (CI).ResultsA total of 14 studies including 1,247,503 participants were short-listed for our analysis. All the studies included in our analysis had a low to moderate risk of bias. The results of our analysis suggest that statins may significantly reduce the risk of developing NAFLD (OR:0.69, 95% CI [0.57,0.84]; p = 0.0002; I² =36%). Statin use significantly reduced ALT levels (WMD: -27.28, 95% CI [-43.06, -11.51]; p = 0.0007; I² =90%), AST levels (WMD: -10.99, 95% CI [-18.17, -3.81]; p = 0.003; I² =79%) and GGT levels (WMD: -23.40, 95% CI [-31.82, -14.98]; p < 0.00001; I² = 21%) in patients presenting with NAFLD at baseline. In liver histology outcomes, steatosis grade (SMD: -2.59, 95% CI [-4.61, -0.56]; p = 0.01; I² = 95%), NAS (WMD: -1.03, 95% CI [-1.33, -0.74]; p < 0.00001; I² = 33%), necro-inflammatory stage (WMD: -0.19, 95% CI [-0.26, -0.13]; p < 0.00001; I² = 0%) and significant fibrosis (OR:0.20, 95% CI [0.04, 0.95]; p = 0.04; I² = 97%) underwent notable reduction. However, fibrosis stage outcome (WMD: 0.07, 95% CI [-0.05, 0.20]; p = 0.27; I² = 0%) was non-significant.ConclusionThere was a significant decrease in transaminase and transferase levels. Marked improvement in liver histology of NAFLD patients was observed. Statin use also remarkably reduced the risk of developing NAFLD. Future large-scale trials can further aid in identifying the positive impact of statins in treatment for NAFLD and those at risk of developing it.