OBJECTIVETo conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes.RESEARCH DESIGN AND METHODSWe searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite.RESULTSWe identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 [1.24–1.48]; I2 = 9.5%), 36% for leucine (1.36 [1.17–1.58]; I2 = 37.4%), 35% for valine (1.35 [1.19–1.53]; I2 = 45.8%), 36% for tyrosine (1.36 [1.19–1.55]; I2 = 51.6%), and 26% for phenylalanine (1.26 [1.10–1.44]; I2 = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 [0.81–0.96] and 0.85 [0.82–0.89], respectively; both I2 = 0.0%).CONCLUSIONSIn studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.

The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). Methods: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. Results: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH 2 O. Values of respiratory system compliance 35 (27-45) ml/cmH 2 O, plateau pressure 25 (22-29) cmH 2 O, and driving pressure 12 (10-16) cmH 2 O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. Conclusions: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.

The Mediterranean diet (MedDiet), abundant in minimally processed plant-based foods, rich in monounsaturated fat from olive oil, but lower in saturated fat, meats, and dairy products, seems an ideal nutritional model for cardiovascular health. Methodological aspects of Mediterranean intervention trials, limitations in the quality of some meta-analyses, and other issues may have raised recent controversies. It remains unclear whether such limitations are important enough as to attenuate the postulated cardiovascular benefits of the MedDiet. We aimed to critically review current evidence on the role of the MedDiet in cardiovascular health. We systematically searched observational prospective cohorts and randomized controlled trials which explicitly reported to assess the effect of the MedDiet on hard cardiovascular end points. We critically assessed all the original cohorts and randomized controlled trials included in the 5 most comprehensive meta-analyses published between 2014 and 2018 and additional prospective studies not included in these meta-analyses, totaling 45 reports of prospective studies (including 4 randomized controlled trials and 32 independent observational cohorts). We addressed the existing controversies on methodology and other issues. Some departures from individual randomization in a subsample of the landmark Spanish trial (PREDIMED [Prevención con Dieta Mediterránea]) did not represent any clinically meaningful attenuation in the strength of its findings and the results of PREDIMED were robust in a wide range of sensitivity analyses. The criteria for causality were met and potential sources of controversies did not represent any reason to compromise the main findings of the available observational studies and randomized controlled trials. The available evidence is large, strong, and consistent. Better conformity with the traditional MedDiet is associated with better cardiovascular health outcomes, including clinically meaningful reductions in rates of coronary heart disease, ischemic stroke, and total cardiovascular disease.