A causal relationship between alcohol intake and type 2 diabetes mellitus: A two-sample Mendelian randomization study

Background and aimsWe investigated whether alcohol intake has a causal relationship with type 2 diabetes mellitus (T2DM) risk in adults of the Korean Genomic Epidemiology Study using two-sample Mendelian randomization (MR) analysis.Methods and resultsDaily alcohol intake was calculated based on the type, average amount, and frequency of alcohol consumption for six months before the interview. The participants were divided into low- and high-alcohol intake of 20 g/day. After adjusting for the covariates related to T2DM, the independent genetic variants (instrumental variables) related to alcohol intake were explored by GWAS analysis in a city hospital-based cohort (n = 58,701). SNPs with a significant level of p-value <5 × 10^?8 and linkage disequilibrium of r² < 0.001 were retrieved. MR methods were used to analyze the causality between alcohol intake and the T2DM risk, and the heterogeneity and leave-one-out sensitivity analyses were conducted in Ansan/Ansung plus rural cohorts (n = 13,598). High alcohol intake increased T2DM risk when the inverse-variance weighted (P = 0.012) and weighted median (P = 0.034) methods were used, but not when the MR-Egger method was used. No significant heterogeneity and horizontal pleiotropy between alcohol intake and T2DM were detected. A single genetic variant did not affect the causal association in a leave-one-out sensitivity analysis.ConclusionThis study supports that heavy alcohol intake appears to be causally associated with T2DM risk.     

Effects of Diet and Sodium Reduction on Cardiac Injury,Strain, and Inflammation: The DASH-Sodium Trial

BackgroundThe DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.ObjectivesThe purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.MethodsDASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.ResultsOf the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: ?27% to ?7%) and hs-CRP by 13% (95% CI: ?24% to ?1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: ?24% to ?14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: ?31% to ?7%) and NT-proBNP by 23% (95% CI: ?32% to ?12%), whereas hs-CRP was not significantly changed (?7%; 95% CI: ?22% to 9%) compared with the high sodium-control diet.ConclusionsCombining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608)     

Carbohydrate intake and risk of metabolic syndrome: A dose–response meta-analysis of observational studies

Background and aimsEpidemiological association studies have reported inconsistent findings on the relationship between carbohydrate intake and risk of metabolic syndrome (MetS). Therefore, we aimed to conduct the first dose–response meta-analysis to investigate this effect.Methods and resultsA systematic search in PubMed and Web of Science databases from their inception to June 01, 2019, together with relevant literature scrutiny, was performed to identify related studies for inclusion into the meta-analysis. We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Furthermore, subgroup, sensitivity, heterogeneity, and publication bias analyses were performed. This meta-analysis included 14 cross-sectional and four cohort studies, totaling 284,638 participants and 69,554 MetS cases. The highest versus the lowest carbohydrate intake values were associated with an increased risk of MetS (OR: 1.253, 95% CI: 1.147–1.368), with moderate heterogeneity (I² = 54.5%). Using dose–response analysis, we found a linear association between carbohydrate consumption and MetS risk with a corresponding OR of 1.026 (95% CI, 1.004–1.048) and with significant heterogeneity (I² = 82.0%) at 5% energy intake from carbohydrates. We have found similar results using subgroup analyses for major study characteristics and adjustment for confounders. Sensitivity analysis further enhanced the robustness of the results, and no publication bias was detected.ConclusionCarbohydrate intake is associated with an increased risk of developing MetS. Therefore, additional large prospective cohort studies are warranted to confirm our findings.     

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).     

Treatment of Resistant Hypertension With Endovascular Baroreflex Amplification: 3-Year Results From the CALM-FIM Study

ObjectivesThe aim of this study was to evaluate the long-term (3-year) safety and effectiveness of endovascular baroreflex amplification (EVBA) from both the European and American CALM-FIM cohorts.BackgroundThe CALM-FIM study demonstrated that EVBA in patients with resistant hypertension significantly lowered blood pressure (BP) with an acceptable safety profile during 6-month follow-up.MethodsThe CALM-FIM studies were prospective, nonrandomized, first-in-human studies that enrolled patients with resistant hypertension (office systolic BP ≥160 mm Hg and mean 24-hour ambulatory BP ≥130/80 mm Hg despite a stable regimen of ≥3 antihypertensive medications, including a diuretic agent). The incidence of (serious) adverse events and changes in BP, heart rate, and prescribed antihypertensive medication up to 3 years after implantation were determined.ResultsThe Mobius device was implanted in 47 patients (30 in Europe, 17 in the United States; mean age 54 years, 23 women). Five serious adverse events (hypotension, n = 2; hypertension, n = 1; vascular access complications, n = 2) and 2 transient ischemic attacks occurred within 30 days postprocedure. Two strokes and 1 transient ischemic attack occurred more than 2 years postimplantation. Mean office BP at baseline was 181 ± 17/107 ± 16 mm Hg and decreased by 25/12 mm Hg (95% CI: 17-33/8-17 mm Hg) at 6 months and 30/12 mm Hg (95% CI: 21-38/8-17 mm Hg) at 3 years. Mean 24-hour ambulatory BP at baseline was 166 ± 16/98 ± 15 mm Hg and decreased by 20/11 mm Hg (95% CI: 14-25/8-15 mm Hg) at 6 months.ConclusionsEVBA with the MobiusHD was effective in reducing BP at 3-year follow-up and appears to have an acceptable safety profile in patients with uncomplicated implantation, although data from randomized sham-controlled trials are needed to further evaluate the risk-benefit profile. (Controlling and Lowering Blood Pressure With the MobiusHD? [CALM-FIM_EUR], NCT01911897; Controlling and Lowering Blood Pressure With the MobiusHD? [CALM-FIM_US], NCT01831895)     

Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis

AimsSeveral health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters [FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c)] vs. control.Data synthesisWe pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I²). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: ?0.07; 95% CI: ?0.20, 0.07; I² = 0.0%), insulin (SMD: ?0.32; 95% CI: ?0.70, 0.06; I² = 38.0%), and HOMA-IR (SMD: ?0.32; 95% CI: ?0.75, 0.10; I² = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results.ConclusionAlthough EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters.     

Effects of dairy products consumption on inflammatory biomarkers among adults: A systematic review and meta-analysis of randomized controlled trials

AimsThis study aimed to summarize earlier studies on the effects of dairy consumption on inflammatory biomarkers in adults and to quantify these effects through meta-analysis.Data synthesisA comprehensive search of all relevant articles, published up to December 2019 indexed in PubMed, ISI (Institute for Scientific Information), EmBase, Scopus, and Google Scholar was done using relevant keywords. Randomized controlled trials (RCTs) that examined the effect of dairy products consumption, compared with low or no dairy intake, on inflammatory biomarkers in adults were included. Overall, 11 RCTs with 663 participants were included in this meta-analysis. We found that high consumption of dairy products, compared with low or no dairy intake, might significantly reduce CRP [weighed mean difference (WMD): −0.24 mg/L; 95% CI, −0.35, −0.14], TNF-α (WMD:- 0.66 pg/mL; 95% CI, −1.23, −0.09), IL-6 (WMD: −0.74 pg/mL; 95% CI, −1.36, −0.12), and MCP concentrations (WMD: −25.58 pg/mL; 95% CI, −50.31, −0.86). However, when the analyses were confined to cross-over trials, no such beneficial effects of dairy intake on inflammation were observed. In addition, high dairy intake might result in increased adiponectin levels (WMD: 2.42 μg/mL; 95% CI, 0.17, 4.66). No significant effect of dairy consumption on serum leptin (WMD: −0.32 ng/mL; 95% CI, −3.30, 2.65), ICAM-1 (WMD: −3.38 ng/ml; 95% CI, −15.57, 8.96) and VCAM-1 (WMD: 3.1 ng/mL; 95% CI, −21.38, 27.58) levels was observed.ConclusionsIn summary, the current meta-analysis indicated that dairy intake might improve several inflammatory biomarkers in adults. In most subgroups without heterogeneity, effects tended to be null. Study design and participants’ age were the main sources of heterogeneity. More research, with a particular focus on fat content of dairy foods, is recommended.     

Age at menopause,body mass index,and risk of type 2 diabetes mellitus in postmenopausal Chinese women: The Henan Rural Cohort study

Background and aimThe present study was conducted to explore the stratified and joint effects of age at menopause and body mass index (BMI) with the risk of type 2 diabetes mellitus (T2DM) in Chinese rural adults.Methods and resultsA total of 15,406 postmenopausal Chinese women were included in this study. Multivariable logistic regression analysis was used to quantify the stratified and joint effects of age at menopause and BMI on T2DM. Overall, the mean age at menopause and BMI was 48.8 ± 4.7 years and 25.1 ± 3.6 kg/m², respectively. In general, data suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, later menopause had a higher risk of T2DM (OR, 1.52; 95% CI, 1.16–2.01); 3) the risk of T2DM was higher only in patients with early or normal age at menopause and BMI ≥ 24, with 0R (95% CI) of (1.58, 1.28–1.94) and (1.48, 1.31–1.67), respectively.ConclusionOur findings suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, a higher risk of T2DM was found only in those with later menopause; 3) women with later menopause had a higher risk of T2DM, irrespective of BMI; 4) in patients with early or normal age at menopause, a higher risk of T2DM was found only in patients with BMI ≥ 24.The Chinese Clinical Trial RegistrationChiCTR–OOC–1500669(URL:http://www.chictr.org.cn/showproj.aspx?proj=11375)     

Carbohydrate quality,glycemic index,glycemic load and cardiometabolic risks in the US,Europe and Asia: A dose–response meta-analysis

Background and aimsDespite the proven evidence of high glycemic index (GI) and glycemic load (GL) diets to increase cardiometabolic risks, knowledge about the meta-evidence for carbohydrate quality within world geographic regions is limited. We conducted a meta-analysis to synthesize the evidence of GI/GL studies and carbohydrate quality, gathering additional exposures for carbohydrate, high glycemic carbohydrate, total dietary fiber, and cereal fiber and risks for type 2 diabetes (T2DM), coronary heart disease (CHD), stroke, and mortality, grouped into the US, Europe, and Asia. Secondary aims examined cardiometabolic risks in overweight/obese individuals, by sex, and dose–response dietary variable trends.Methods and results40-prospective observational studies from 4-Medline bibliographical databases (Ovid, PubMed, EBSCOhost, CINAHL) were search up to November 2019. Random-effects hazard ratios (HR) and 95% confidence intervals (CI) for highest vs. lowest categories and continuous form combined were reported. Heterogeneity (I²>50%) was frequent in US GI/GL studies due to differing study characteristics. Increased risks ((HR_GI,T2DM,US=1.14;CI:1.06,1.21), HR_GL,T2DM,US=1.02 (1.01, 1.03)), HR_GI,T2DM,Asia=1.25;1.02,1.53), and HR_GL,T2DM,Asia=1.37 (1.17, 1.60)) were associated with cardiometabolic diseases. GI/GL in overweight/obese females had the strongest magnitude of risks in US-and Asian studies. Total dietary fiber (HRT2DM,US = 0.92;0.88,0.96) and cereal fiber (HR_T2DM,US = 0.83;0.77,0.90) decreased risk of developing T2DM. Among females, we found protective dose–response risks for total dietary fiber (HR_{5g-total-dietary-fiber,T2DM,US} = 0.94;0.92,0.97)_, but cereal fiber showed better ability to lower T2DM risk (HR_{5g-cereal-fiber},_T2DM,US = 0.67;0.60,0.74). Total dietary-and cereal fibers' dose–response effects were nullified by GL, but not so for cereal fiber with GI.ConclusionsOverweight/obese females could shift their carbohydrate intake for higher cereal fiber to decrease T2DM risk, but higher GL may cancel-out this effect.     

Impact of whole egg intake on blood pressure,lipids and lipoproteins in middle-aged and older population: A systematic review and meta-analysis of randomized controlled trials

Background and aimEffects of whole egg consumption on cardiovascular diseases (CVD) risk in the middle-aged and older population remain unclear due to inconsistent findings from observational and randomized controlled trials (RCTs). This meta-analysis aimed to assess the impacts of whole egg and egg category (whole eggs versus egg substitutes) intake quantity on CVD risk factors from systematically searched RCTs. Egg substitutes were hypothesized to have minimal effects of the blood lipid and lipoprotein profile as they are void of dietary cholesterol.Methods and resultsAs many as 434 studies identified from PubMed, Cochrane Library, CINAHL and Medline (Ovid) databases were screened and data were extracted from 8 selected RCTs. Quality of the selected studies were assessed and the overall effect sizes of weighted mean differences (WMD) were calculated using a random effects model. Non-differential effects in blood pressures, lipids and lipoproteins were observed when >4 whole eggs/week compared to ≤4 whole eggs/week were consumed. Intake of >4 whole eggs/week compared to equivalent amounts of egg substitutes caused greater elevations in blood total cholesterol (WMD: 0.198 mmol/L; 95% CIs: 0.056, 0.339), HDL cholesterol (WMD: 0.068 mmol/L; 95% CIs: 0.006, 0.130) and LDL cholesterol (WMD: 0.171 mmol/L; 95% CIs: 0.028, 0.315) but did not differentially affect triglycerides concentration.ConclusionOverall, the results support the notion that quantity of whole egg intake does not affect CVD risk factors and consuming egg substitutes may also be beneficial compared to whole eggs on lowering CVD risk in the middle-aged and older population.     

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy

BackgroundLeft ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.ObjectivesThis study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.MethodsPatients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout.ResultsFrom baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: ?40 ± 27 mm Hg, and ?43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (?36 ± 27 mm Hg and ?53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (?6% ± 7.5% and ?12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro–B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms.ConclusionsAficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.     

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes

Background and aimsDuring aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0–10.0 mmol/L) during PA in people with T1D.Methods and resultsAn open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO_2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI.ConclusionsIn people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies.ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).     

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes

Background and aimsSeasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D).Methods and resultsRetrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: ?1.33%, Δs-w UKPDS-Stroke: ?0.84%, Δs-w ASCVD: ?2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r² = 0.43) and the ASCVD (r² = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r² = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors.ConclusionsSeasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.     

Effects of nut consumption on blood lipid profile: A meta-analysis of randomized controlled trials

Background & aimsSeveral randomized controlled trials (RCTs) have assessed the effects of nut consumption on blood lipid profile. The aim of this study was to conduct a meta-analysis to quantitatively estimate the effects of nut consumption on blood lipid profile.Methods and resultsThe PubMed, EMBASE, Cochrane Library, and Google Scholar databases were systematically searched to identify RCTs examining the effects of nut intake on blood total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) from inception until March 2021. A random-effects model was used to pool standardized mean differences (SMDs) and 95% confidence intervals (CIs). Potential publication bias was assessed using Begg's test and Egger's test. Sensitivity analysis was performed to assess the impact of each individual study on the pooled results. The meta-analysis showed that nut consumption had no significant effect on the blood lipid profile. However, there was a significant reduction in TC (SMD: ?2.89, 95% CI: ?4.80, ?0.98, I² = 97.4) for pistachio consumption, and cashew consumption significantly increased HDL-C (SMD: 0.24, 95% CI: 0.04, 0.43, I² = 0.0) compared with that in controls. There was no significant publication bias in the meta-analysis. The sensitivity analysis showed that removing one study at a time did not change the significance of the results.ConclusionThere was no overall effect of nut consumption on lipid profile, and the results may vary depending on nut type. We found that pistachio consumption may reduce TC levels, while cashew consumption increases HDL-C.Registry numberPROSPERO CRD42021249147.     

Direct Oral Anticoagulants vs Vitamin K Antagonists in Patients With Antiphospholipid Syndromes: Meta-Analysis of Randomized Trials

BackgroundThe efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.ObjectivesThe authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).MethodsWe searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.ResultsOur search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I² = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I² = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I² = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I² = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.ConclusionsPatients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.     

Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis

Introduction and ObjectivesType 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM.Materials and MethodsThe current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events.Results6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001).ConclusionsThe identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.     

Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes

Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM).Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype.ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.     

The ankle-brachial index for assessing the prevalence of peripheral artery disease and cardiovascular risk in patients with type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) is an important risk factor for peripheral artery disease (PAD). Ankle-Brachial Index (ABI) was found associated with a higher cardiovascular (CV) risk and mortality. The main goals of this study were to establish the prevalence of PAD in a T2DM population, and assess the relationship between PAD and the CV risk calculated with the CUORE Project score (CPS) (https://www.cuore.iss.it/). The association between the ABI, the main risk factors for PAD and T2DM complications was also investigated.Methods and resultsTwo hundred patients were consecutively enrolled. The prevalence of PAD in this population was 17%. The CV risk tended to be higher (p = 0.0712) in the group with a pathological ABI than in the group with a normal ABI. Glycated hemoglobin (r = ?0.1591; p = 0.0244), total cholesterol (r = ?0.1958; p = 0.0054), LDL cholesterol (r = ?0.1708; p = 0.0156) and systolic blood pressure (r = ?0.1523; p = 0.0313) correlated significantly and inversely with the left ABI. The frequency of diabetic retinopathy was significantly higher in the group with a pathological ABI (p = 0.0316).ConclusionsThe data reveal a high prevalence of PAD in patients with T2DM. The CPS confirmed that patients with a pathological ABI have tendency to a higher CV risk. The results point to the importance of an accurate CV assessment – also measuring individuals’ ABI and calculating their CPS - to better pinpoint those at high risk of PAD, especially among patients with T2DM.     

Effect of pharmacological interventions and placebo on liver Histology in nonalcoholic steatohepatitis: A network meta-analysis

BackgroundThe aims of this study were to quantify the histological improvement and its risk factors in patients with NASH enrolled in the placebo arms of randomized controlled trials (RCTs), and to indirectly compare the effect of several investigational drugs for NASH on validated histological outcomes.Data synthesisA comprehensive search was conducted to detect phase 2 and 3 RCTs comparing pharmacological interventions in patients with NASH. According to Food and Drug Administration (FDA) recommendations, primary outcomes included: 1) NASH resolution without worsening of fibrosis; 2) At least 1-point reduction in fibrosis without worsening of NASH. Meta-analysis and meta-regressions were conducted on placebo arms, while network meta-analysis was performed on intervention arms.A total of 15 RCTs met the eligibility criteria. The meta-analysis on placebo arms showed a pooled estimate rate of 17% (95%C.I. 12%–23%;I² = 86%; p < 0.01) for NASH resolution without worsening of fibrosis and of 21% (95%C.I. 13%–31%;I² = 84%; p < 0.01) for ≥1stage improvement of fibrosis without worsening of NASH. Phase 3 (vs Phase 2)RCTs, older age and higher AST levels were significantly associated with progression of liver disease by univariate meta-regression. At network meta-analysis, Semaglutide (P-score 0.906), Pioglitazione alone (score 0.890) and plus Vitamin E (0.826) had the highest probability of being ranked the most effective intervention for NASH resolution without worsening of fibrosis, while Aldafermin (0.776), Lanifibranor (0.773) and Obeticholic acid (0.771) had the highest probability to achieve ≥1 stage of fibrosis improvement without worsening of NASH.ConclusionThis study confirms the heterogeneity of histological progression of untreated patients with NASH and provides evidence to stratify patients according to identified risk factors in future RCTs of combination therapies. PROSPERO CRD42021287205.     

Safety and harms of bronchoalveolar lavage for acute respiratory failure: A systematic review and meta-analysis

BackgroundThis review aimed to investigate whether bronchoalveolar lavage (BAL) is safe in patients with severe acute respiratory failure (ARF).MethodsWe searched the MEDLINE, CENTRAL, and other databases up to June 2, 2021 for studies that examined BAL for severe ARF. We included all cohort studies and randomized or non-randomized trials, while we excluded case-control studies, case reports, and case series. We evaluated the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach.ResultsWe included 17 studies (1085 patients) in the meta-analysis. The integrated frequency of death was 0.000% (95% confidence interval [CI]: 0.000–0.045%, I² = 0.0%). The pooled risk of severe complications of respiratory system, cardiovascular system, and major bleeding was 1.32% (95% CI: 0.000–4.41%, I² = 84.8%), 0.040% (95% CI: 0.000–0.71%, I² = 9.3%), and 0.000% (95% CI: 0.000–0.27%, I² = 0.0%), respectively. In the subgroup analysis with mechanical ventilation during BAL, there were few severe complications of the respiratory system (3/717 patients in 13 studies) and almost no heterogeneity (I² = 0.0%).ConclusionsOur study suggests that severe complications of BAL for severe ARF are probably rare, particularly in patients receiving mechanical ventilation. After considering the risks and benefits, it would be worthwhile to consider performing BAL in patients with severe ARF of unknown etiology to pursue its cause.Trial registrationThe protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000040600).