Sex hormone-binding globulin may explain sex differences for glucose homeostasis and incidence of type 2 diabetes: the KORA study.

Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1937, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1387). T2D was initially assessed by self-report and validated by contacting the physicians and/ or reviewing the medical charts. Mediation analyses were performed to assess the role of SHBG in mediating the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower fasting glucose levels compared to men (ß = -4.94 (mg/dl), 95% CI: -5.77, -4.11). SHBG levels were significantly higher in women than in men (ß = 0.47 (nmol/l), 95% CI:0.42, 0.51). Serum SHBG may mediate the association between sex and fasting glucose levels with a proportion mediated (PM) of 30% (CI: 22-41%). Also, a potential mediatory role of SHBG was observed for sex differences in incidence of T2D (PM = 95% and 63% in models 1 and 2, respectively). Our novel findings suggest that SHBG may partially explain sex-differences in glucose control and T2D incidence.

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS: Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS: Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION: Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.

Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis.

AIMS: To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. METHODS AND RESULTS: We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I2: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I2: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I2: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I2: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I2: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (Pnonlinearity > 0.05). CONCLUSION: This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality.

Prognostic models in COVID-19 infection that predict severity: a systematic review.

Current evidence on COVID-19 prognostic models is inconsistent and clinical applicability remains controversial. We performed a systematic review to summarize and critically appraise the available studies that have developed, assessed and/or validated prognostic models of COVID-19 predicting health outcomes. We searched six bibliographic databases to identify published articles that investigated univariable and multivariable prognostic models predicting adverse outcomes in adult COVID-19 patients, including intensive care unit (ICU) admission, intubation, high-flow nasal therapy (HFNT), extracorporeal membrane oxygenation (ECMO) and mortality. We identified and assessed 314 eligible articles from more than 40 countries, with 152 of these studies presenting mortality, 66 progression to severe or critical illness, 35 mortality and ICU admission combined, 17 ICU admission only, while the remaining 44 studies reported prediction models for mechanical ventilation (MV) or a combination of multiple outcomes. The sample size of included studies varied from 11 to 7,704,171 participants, with a mean age ranging from 18 to 93 years. There were 353 prognostic models investigated, with area under the curve (AUC) ranging from 0.44 to 0.99. A great proportion of studies (61.5%, 193 out of 314) performed internal or external validation or replication. In 312 (99.4%) studies, prognostic models were reported to be at high risk of bias due to uncertainties and challenges surrounding methodological rigor, sampling, handling of missing data, failure to deal with overfitting and heterogeneous definitions of COVID-19 and severity outcomes. While several clinical prognostic models for COVID-19 have been described in the literature, they are limited in generalizability and/or applicability due to deficiencies in addressing fundamental statistical and methodological concerns. Future large, multi-centric and well-designed prognostic prospective studies are needed to clarify remaining uncertainties.

Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

The effects of sesame, canola, and sesame-canola oils on cardiometabolic markers in patients with type 2 diabetes: a triple-blind three-way randomized crossover clinical trial.

AIMS: To compare the effects of replacing regular dietary oils intake with sesame (SO), canola (CO), and sesame-canola (SCO) oils (a novel blend), on cardiometabolic markers in adults with type 2 diabetes mellitus (T2DM), in a triple-blind, three-way, randomized, crossover clinical trial. METHODS: Participants were assigned to receive SO, CO, and SCO in three 9-week phases (4 weeks apart). Cardiometabolic makers (serum lipids, Apolipoprotein, cardiovascular risk scores, kidney markers, and blood pressure) were considered at the beginning and the end of intervention phases. RESULTS: Ninety-two, ninety-five, and ninety-five participants completed the SO, SCO, and CO periods, respectively. After CO consumption, serum Apo A-1 concentrations were significantly higher compared with the SCO period in the whole population (p < 0.05). A considerable reduction in visceral adiposity index values was seen in the CO compared with the SO period in males (p < 0.05). Serum high-density lipoprotein concentration was also significantly higher after the SO intake compared with SCO in females (p < 0.05). The between-period analysis showed a substantial reduction in diastolic blood pressure in the SCO period compared with the CO and SO periods and lower systolic blood pressure after SCO versus CO intake in males (p < 0.05). CONCLUSIONS: Canola oil might protect CVD through improving Apo A-1 levels in patients with T2DM (particularly in females) and visceral adiposity index in male patients. However, the blend oil might beneficially affect blood pressure in men. Future sex-specific studies might warrant the current findings. REGISTRY OF CLINICAL TRIALS: This trial was registered in the Iranian Registry of Clinical Trials (IRCT, registration ID: IRCT2016091312571N6).

The effect of sesame, canola, and sesame-canola oils on cardiometabolic risk factors in overweight adults: a three-way randomized triple-blind crossover clinical trial.

Limited data exist on the cardiometabolic effects of sesame oil compared with canola oil. In the present study, 77 overweight adults were randomized to replace their regularly consumed oils with canola (CO), sesame (SO), and sesame-canola oils (SCO, 40% SO, and 60% CO) in three 9-week phases. Blood pressure, visceral adiposity index, serum apo-proteins (APOs) and lipid profile, glycemic control markers, kidney markers, liver enzymes, and cardiovascular disease risk scores were assessed at baseline and endline. After adjustment for confounders, SO significantly reduced serum alkaline aminotransferase (ALT) compared to CO (p ≤ 0.05) in all participants, increased serum urea compared to SCO in males, and decreased serum alkaline phosphatase compared to other oils in males, and improved serum high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) compared to SCO, and eGFR compared with CO in females (p ≤ 0.05). Canola oil significantly improved serum Apo A1 and APO B/A ratio compared with SO, in males (p ≤ 0.05). Sesame-canola oil significantly reduced serum urea compared to other oils in all participants (p ≤ 0.05). Sesame oil and SCO might beneficially affect serum ALT and urea, respectively. Intervention oils might have different cardiometabolic effects in each gender. Further studies are needed to confirm our results (Trial registration code: IRCT2016091312571N6).

Canola oil compared with sesame and sesame-canola oil on glycaemic control and liver function in patients with type 2 diabetes: A three-way randomized triple-blind cross-over trial.

BACKGROUND: This study aimed to compare the effects of sesame (SO), canola (CO), and sesame-canola (SCO: a blend) oils on glycaemic control markers and liver function enzymes in adults with type 2 diabetes. METHODS: In this randomized, triple-blind, three-way, cross-over clinical trial, participants replaced their usual oil with the intervention oils for 9 weeks. Serum fasting blood sugar, fasting serum insulin (FSI), insulin resistance (HOMA2-IR), beta-cell function (HOMA2-%B), insulin sensitivity (HOMA2-%S), quantitative insulin sensitivity check index (QUICKI), as well as serum liver function enzymes were measured at baseline and end of intervention periods. RESULTS: Ninety-two participants completed all treatment periods. After adjusting for confounders, all treatment oils resulted in significant improvements in FSI and HOMA2-%S (p < 0.05). SO and SCO led to favourable changes in HOMA2-IR and QUICKI (p < 0.05). Following CO and SCO, there was a significant decrease in HOMA2-%B (p < 0.05). The sex-stratified analysis revealed that FSI and HOMA2-IR were decreased after SO compared to CO in males (p = 0.024). Serum gamma-glutamyltransferase (GGT) was significantly lower following SO compared to CO in females (p = 0.02), however, the difference in change values was not significant (p = 0.058). CONCLUSIONS: SO consumption appears to improve glycaemic control markers in males and serum GGT in females compared with CO in patients with type 2 diabetes (registration code: IRCT2016091312571N6).

Meta-analysis of vitamin D supplementation and hemoglobin concentration: methodological faults obscure the interpretation of the data.

We read the review by Arabi et al. with great interest which tried to examine the effects of vitamin D supplementation on hemoglobin concentration. It seems that the article suffers from fundamental methodological issues and the conclusions are likely to be erroneous. In this regard, we would like to ask the authors to address the mentioned limitations and to update the analysis in order to provide robust and trustful results. We are concerned that such meta-analyses may lead to the biased findings and conclusions.

The effect of canola, sesame and sesame-canola oils on body fat and composition in adults: a triple-blind, three-way randomised cross-over clinical trial.

The present study aimed to examine the effect of replacing edible oils with sesame oil (SO), canola oil (CO) and sesame-canola oil (SCO) on body weight and composition in adults. Adults without any chronic diseases (n = 77) were entered a 4-week run-in period and then were randomised to receive SO, CO and SCO for their household use in 9-week intervention periods (separated by 4-week washout intervals). Anthropometric measurements, as well as body composition markers, were assessed at baseline, middle and after each intervention period. In total, 73 participants completed the study. Although significant time effects were seen for waist and hip circumference, waist-to-hip ratio, central obesity index, body adiposity index, muscle mass and body fat percent (ptime<.05), the treatment and treatment × time effects were not significant (p>.05). The present clinical trial revealed that CO, SO and SCO might not differently affect body fat and composition. Trial registration code: IRCT2016091312571N6 (http://en.irct.ir/trial/12622).

Effects of sesame, canola and sesame-canola oils on body weight and composition in adults with type 2 diabetes mellitus: a randomized, triple-blind, cross-over clinical trial.

BACKGROUND: Recent investigations have proposed that sesame and canola oils might affect body fat distribution. The present study aimed to examine the effects of sesame, canola and sesame-canola (a blend of sesame and canola oils) oils on body weight and composition in adults with type 2 diabetes mellitus in the context of a randomized, triple-blind, three-way, cross-over clinical trial. RESULTS: Eligible participants were randomized to replace their regular dietary oil with sesame oil (SO), canola oil (CO) and sesame-canola oil (SCO) (with 40% SO and 60% CO). Treatment periods lasted 9 weeks and were separated by 4-week wash-out periods. Body weight and composition were measured at the beginning, in the middle and at the end of each intervention phase. In total, 93 participants completed the study. After adjustment for confounders, within-period changes were observed following SO and CO intake for body weight (0.34 ± 0.16 kg and 0.33 ± 0.17 kg) and visceral fat (0.13 ± 0.06% and 0.13 ± 0.05%, P < 0.05), respectively. Body mass index was increased within SO intake (0.13 ± 0.05 kg m-2 , P = 0.031). All of the treatment oils resulted in reduced waist circumference and index of central obesity (P < 0.05). A significant difference in change values was observed for visceral fat between SCO (-0.14 ± 0.07%) and SO (0.12 ± 0.08%) treatment periods in females (P = 0.02). CONCLUSION: Sesame and canola oils might lead to a modest favorable body fat redistribution by reducing central adiposity, particularly in females; however, the changes were of little clinical importance. © 2021 Society of Chemical Industry.

The effects of Canola oil on cardiovascular risk factors: A systematic review and meta-analysis with dose-response analysis of controlled clinical trials.

BACKGROUND AND AIMS: Canola oil (CO) is a plant-based oil with the potential to improve several cardiometabolic risk factors. We systematically reviewed controlled clinical trials investigating the effects of CO on lipid profiles, apo-lipoproteins, glycemic indices, inflammation, and blood pressure compared to other edible oils in adults. METHODS AND RESULTS: Online databases were searched for articles up to January 2020. Forty-two articles met the inclusion criteria. CO significantly reduced total cholesterol (TC, -0.27 mmol/l, n = 37), low-density lipoprotein cholesterol (LDL-C, -0.23 mmol/l, n = 35), LDL-C to high-density lipoprotein cholesterol ratio (LDL/HDL, -0.21, n = 10), TC/HDL (-0.13, n = 15), apolipoprotein B (Apo B, -0.03 g/l, n = 14), and Apo B/Apo A-1 (-0.02, n = 6) compared to other edible oils (P < 0.05). Compared to olive oil, CO decreased TC (-0.23 mmol/l, n = 9), LDL-C (-0.17 mmol/l, n = 9), LDL/HDL (-0.39, n = 2), and triglycerides in VLDL (VLDL-TG, -0.10 mmol/l, n = 2) (P < 0.05). Compared to sunflower oil, CO improved LDL-C (-0.14 mmol/l, n = 11), and LDL/HDL (-0.30, n = 3) (P < 0.05). In comparison with saturated fats, CO improved TC (-0.59 mmol/l, n = 11), TG (-0.08 mmol/l, n = 11), LDL-C (-0.49 mmol/l, n = 10), TC/HDL (-0.29, n = 5), and Apo B (-0.09 g/l, n = 4) (P < 0.05). Based on the nonlinear dose-response curve, replacing CO with ~15% of total caloric intake provided the greatest benefits. CONCLUSION: CO significantly improved different cardiometabolic risk factors compared to other edible oils. Further well-designed clinical trials are warranted to confirm the dose-response associations.

Comparison of blood lipid-lowering effects of olive oil and other plant oils: A systematic review and meta-analysis of 27 randomized placebo-controlled clinical trials.

Objective: We aim to report a systematic review and meta-analysis of randomized controlled trials (RCTs) on effects of olive oil consumption compared with other plant oils on blood lipids. Methods: PubMed, web of science, Scopus, ProQuest, and Embase were systematically searched until September 2017, with no age, language and design restrictions. Weighed mean difference (WMD) and 95% confidence interval (CI) were expressed as effect size. Sensitivity analyses and pre specified subgroup was conducted to evaluate potential heterogeneity. Meta-regression analyses were performed to investigate association between blood lipid-lowering effects of olive oil and duration of treatment. Results: Twenty-seven trials, comprising 1089 participants met the eligibility criteria. Results of this study showed that compared to other plant oils, high-density lipoprotein level increased significantly more for OO (1.37 mg/dl: 95% CI: 0.4, 2.36). Also OO consumption reduced total cholesterol (TC) (6.27 mg/dl, 95% CI: 2.8, 10.6), Low-density lipoprotein (LDL-c) (4.2 mg/dl, 95% CI: 1.4, 7.01), and triglyceride (TG) (4.31 mg/dl, 95% CI: 0.5, 8.12) significantly less than other plant oils. There were no significant effects on Apo lipoprotein A1 and Apo lipoprotein B. Conclusion: This meta-analysis suggested that OO consumption decreased serum TC, LDL-c, and TG less but increased HDL-c more than other plant oils.

Substituting Low-Calorie Sweetened Beverages for Sugar-Sweetened Beverages to Prevent Obesity and Cardiometabolic Diseases: Still a Good Idea?

Low-calorie sweeteners (LCSs) and LCS-containing beverages have been proposed as appropriate substitutes for caloric sugars in recent years. In this Perspective, we highlight the recent findings from observational and interventional studies, focusing on obesity, gut microbiome, and cardiometabolic health. We provide public health actors and health care professionals with an insightful overview of recent evidence to bridge the gap between research and practice.

Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies.

CONTEXT: Several effects of non-sugar-sweetened beverage (NSSBs) intake on health outcomes have been reported; however, the evidence on the association between NSSBs intake and chronic diseases and mortality risk is still inconclusive. OBJECTIVE: This umbrella review aimed to summarize the evidence on the association between NSSBs intake and the risk of chronic diseases and mortality. DATA SOURCES: Embase, ISI Web of Science, Cochrane Central, and PubMed were searched up to September 2023 for relevant meta-analyses of observational prospective cohort studies. DATA EXTRACTION: Two groups of researchers independently extracted study data and assessed the risk of bias for meta-analyses and primary studies. DATA ANALYSIS: Six meta-analyses, reporting 74 summary hazard ratios (HRs) for different outcomes obtained from 50 primary studies, were included. The summary HRs, 95% CIs, and certainty of evidence on the association of NSSBs intake with risk of chronic diseases and mortality were as follows: all-cause mortality (per 355 mL/d: 1.06 [1.01 to 1.10]; moderate certainty); stroke (per 250 mL/d: 1.09 [1.04 to 1.13]; high certainty); coronary heart disease (CHD) (per 250 mL/d: 1.06 [1.02 to 1.11]; high certainty); hypertension (HTN) (high vs low intake: 1.14 [1.09 to 1.18]; moderate certainty); type 2 diabetes (T2D) (high vs low intake: 1.16 [1.08 to 1.26]; low certainty); metabolic syndrome (MetS) (high vs low intake: 1.32 [1.22 to 1.43]; low certainty); colorectal cancer (high vs low intake: 0.78 [0.62 to 0.99]; moderate certainty); and leukemia (high vs low intake: 1.35 [1.03 to 1.77]; moderate certainty). For other outcomes, including the risk of cardiovascular and cancer mortality, chronic kidney diseases, breast cancer, prostate cancer, endometrial cancer, pancreatic cancer, multiple myeloma, and non-Hodgkin lymphoma, no association was found. CONCLUSION: This study provides further evidence that NSSBs are associated with increased risk of all-cause mortality, stroke, CHD, HTN, T2D, MetS, and leukemia. Moreover, a higher intake of NSSBs was associated with a lower risk of colorectal cancer. However, it should be noted that the magnitudes of the associations are not large. Further studies are needed to clarify the long-term effects of different NSSBs intakes on health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023429981.

Agreement Between Mega-Trials and Smaller Trials: A Systematic Review and Meta-Research Analysis.

Importance: Mega-trials can provide large-scale evidence on important questions. Objective: To explore how the results of mega-trials compare with the meta-analysis results of trials with smaller sample sizes. Data Sources: ClinicalTrials.gov was searched for mega-trials until January 2023. PubMed was searched until June 2023 for meta-analyses incorporating the results of the eligible mega-trials. Study Selection: Mega-trials were eligible if they were noncluster nonvaccine randomized clinical trials, had a sample size over 10 000, and had a peer-reviewed meta-analysis publication presenting results for the primary outcome of the mega-trials and/or all-cause mortality. Data Extraction and Synthesis: For each selected meta-analysis, we extracted results of smaller trials and mega-trials included in the summary effect estimate and combined them separately using random effects. These estimates were used to calculate the ratio of odds ratios (ROR) between mega-trials and smaller trials in each meta-analysis. Next, the RORs were combined using random effects. Risk of bias was extracted for each trial included in our analyses (or when not available, assessed only for mega-trials). Data analysis was conducted from January to June 2024. Main Outcomes and Measures: The main outcomes were the summary ROR for the primary outcome and all-cause mortality between mega-trials and smaller trials. Sensitivity analyses were performed with respect to the year of publication, masking, weight, type of intervention, and specialty. Results: Of 120 mega-trials identified, 41 showed a significant result for the primary outcome and 22 showed a significant result for all-cause mortality. In 35 comparisons of primary outcomes (including 85 point estimates from 69 unique mega-trials and 272 point estimates from smaller trials) and 26 comparisons of all-cause mortality (including 70 point estimates from 65 unique mega-trials and 267 point estimates from smaller trials), no difference existed between the outcomes of the mega-trials and smaller trials for primary outcome (ROR, 1.00; 95% CI, 0.97-1.04) nor for all-cause mortality (ROR, 1.00; 95% CI, 0.97-1.04). For the primary outcomes, smaller trials published before the mega-trials had more favorable results than the mega-trials (ROR, 1.05; 95% CI, 1.01-1.10) and subsequent smaller trials published after the mega-trials (ROR, 1.10; 95% CI, 1.04-1.18). Conclusions and Relevance: In this meta-research analysis, meta-analyses of smaller studies showed overall comparable results with mega-trials, but smaller trials published before the mega-trials gave more favorable results than mega-trials. These findings suggest that mega-trials need to be performed more often given the relative low number of mega-trials found, their low significant rates, and the fact that smaller trials published prior to mega-trial report more beneficial results than mega-trials and subsequent smaller trials.

Two cosmoses, one universe: a narrative review exploring the gut microbiome's role in the effect of urban risk factors on vascular ageing.

In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.

Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (ß = -.01; 95% CI -0.02, -0.01) and FPI (ß = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.