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Aims/hypothesisHyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes.MethodsWe conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years).ResultsSix hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1–2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3–4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1–6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively.Conclusions/interpretationFBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders.

Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism of peripheral Y1R, via the non-brain penetrable antagonist BIBO3304, leads to a significant reduction in body weight gain due to enhanced EE thereby reducing fat mass. Specifically thermogenesis in brown adipose tissue (BAT) due to elevated UCP1 is enhanced accompanied by extensive browning of white adipose tissue both in mice and humans. Importantly, selective ablation of Y1R from adipocytes protects against diet-induced obesity. Furthermore, peripheral specific Y1R antagonism also improves glucose homeostasis mainly driven by dynamic changes in Akt activity in BAT. Together, these data suggest that selective peripheral only Y1R antagonism via BIBO3304, or a functional analogue, could be developed as a safer and more effective treatment option to mitigate diet-induced obesity. Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.

Background Several studies have suggested that the gut microbiota (GM) may be associated with type 2 diabetes mellitus (T2DM). However, the causal relationship between GM and T2DM and whether inflammatory cytokines act as mediators remain unclear. Aims To investigate the association between GM and T2DM and the proportion of this association that is mediated through inflammatory cytokines. Methods We conducted a bidirectional and mediation Mendelian randomization (MR) study utilizing data from the genome-wide association studies (GWAS) of four sources of GM taxa (MiBioGen consortium, n  = 18,340; Dutch Microbiome Project, n  = 7,738; German biobanks, n  = 8,956; FINRISK 2002, n  = 5,959), a meta-analysis of inflammatory proteins ( n  = 14,824), and European-ancestry T2DM ( n  = 1,528,967). The inverse variance weighted method was applied as the primary method. And two-step MR was employed to identify potential mediating inflammatory cytokines. Results We found evidence for 28 positive and 20 negative causal effects between multiple sources of GM and T2DM using at least two MR methods. And there were 2 positive and 5 negative causal relationships between cytokines and T2DM using at least two MR methods. The mediation MR analysis found that interferon-gamma (IFN-γ) mediated the causal effects of species Kandleria vitulina on T2DM (proportion mediated = 22.5%, P  = 0.022). Conclusion The MR study supports the causal effect between Kandleria vitulina species and T2DM, with a potential mediating role played by inflammatory factor IFN-γ. Such result would serve as evidence for GM-targeted and cytokine-targeted therapy to prevent T2DM.

Background Recent advancements in medical education underscore the importance of training professionals who are proficient in multiple disciplines. This study aims to develop clinical data analysis cases centered around diseases by utilizing public datasets, and to investigate the establishment of a “medicine + X” simulation practice system within the framework of interdisciplinary disciplines. Methods From a multi-disciplinary perspective, we designed a cross-disciplinary “medicine + X” subject simulation practice system based on three dimensions: data, case, and simulation. This system comprises three parts: dataset classification, dataset modeling, and dataset clinical analysis. The entire interdisciplinary simulation system adheres to the concept of functional modular design and employs a model stratification method to achieve the division of data, analysis, and presentation models. This creates a closed-loop practice that spans data sample selection and processing to front-end interaction. Finally, we used a modified version of the System Usability Scale (SUS) questionnaire to evaluate the interdisciplinary simulation system. Results Five cases of gout, gastritis, cirrhosis, inflammatory bowel disease, and chronic obstructive pulmonary disease were utilized to master the standard process of data analysis across various datasets from multiple dimensions of the model algorithm, data analysis, and result display. Conclusion The “Data-case-simulation” trinity practice teaching model enables students to utilize open-source datasets for case analysis, employing clinical index modeling and statistical thinking. This verifies the efficiency of case simulation analysis within interdisciplinary scenarios and provides a data-driven practice paradigm for medical education innovation. This model holds significant reference value for promoting in-depth cross-disciplinary integration of “medicine + X”.

Diabetic retinopathy (DR) remains as the most frequent complication of diabetes, and is the major cause of vision loss for middle-aged to elderly people. With longer life expectancies for people with diabetes, there is a significant rise in diabetic retinopathy worldwide. The treatment of DR is limited; and therefore, our study aimed to investigate the possibilities of circulating exosomal miRNAs in the early screening and prevention of DR; and to explore the function of the exosomal miRNAs in DR. Eighteen participants were recruited and divided into two groups: the diabetes mellitus (DM) group and the DR group. We analyzed the expression profile of exosomal miRNAs derived from serum using RNA sequencing. Additionally, we conducted co-culture experiments of RGC-5 and HUVEC cells with DR-derived exosomes to examine the role of highly expressed exosomal miRNA-3976 in DR. Furthermore, we transfected RGC-5 and HUVEC cells with miRNA-3976 to investigate its effects. Among the 1059 miRNAs analyzed, we identified eighteen up-regulated exosomal miRNAs. Treatment with DR-derived exosomes resulted in increased proliferation and reduced apoptosis of RGC-5 cells, and these effects were partially reversed by the miRNA-3976 inhibitor. Moreover, over-expression of miRNA-3976 led to increased apoptosis of RGC-5 cells and indirectly reduced the abundance of NFκB1. Serum-derived exosomal miRNA-3976 has the potential to serve as a biomarker for DR, primarily exerting its effects in the early stages of DR through the regulation of NFκB-associated mechanisms.

Background Previous studies have reported that high fasting plasma glucose (FPG), even that within the normal range, is associated with the risk of type 2 diabetes (T2D). Nevertheless, these findings are limited to specific populations. Thus, studies in the general population are imperative. Methods This study included two cohorts comprising 204 640 individuals who underwent physical examinations at the Rich Healthcare Group present at 32 locations in 11 cities of China from 2010 to 2016 and 15 464 individuals who underwent physical tests at the Murakami Memorial Hospital in Japan. Cox regression, restricted cubic spline (RCS), Kaplan–Meier (KM) curves, and subgroup analysis were used to determine the relationship between FPG and T2D. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of FPG for T2D. Results The mean age of the 220 104 participants (204 640 Chinese and 15 464 Japanese participants) was 41.8 years (41.7 years for the Chinese and 43.7 years for the Japanese participants). During follow-up, 2611 individuals developed T2D (2238 Chinese and 373 Japanese participants). The RCS demonstrated a J-shaped relationship between FPG and T2D risk, with inflexion points of 4.5 and 5.2 for the Chinese and Japanese populations, respectively. Multivariate-adjusted hazard ratio (HR) was 7.75 for FPG and T2D risk after the inflexion point (7.3 for Chinese and 21.13 for Japanese participants). Conclusions In general Chinese and Japanese populations, the normal baseline FPG range showed a J-shaped relationship with the risk of T2D. Baseline FPG levels help identify individuals at high risk of T2D and may enable early primary prevention to improve their outcomes.

Background Studies have reported that lipid-derived indicators are associated with type 2 diabetes (T2D) in various populations; however, it is unclear which lipid-derived indicators could effectively predict T2D risk. Therefore, this study aimed to explore the association between four lipid-derived indicators and T2D risk. Methods This was a post-hoc analysis from a large cohort that included data from 114,700 Chinese individuals aged 20 years and older from 11 cities and 32 sites. The association between four lipid-derived indicators and T2D risk was determined using Kaplan-Meier (KM) survival curves, Cox regression, and restricted cubic spline analyses. This study used receiver operating characteristic (ROC) curves for assessing the ability of four lipid-derived indicators to accurately predict the development of T2D during follow-up. Results This study included a total of 114,700 participants, with a mean age of 44.15. These individuals were followed up for 3.1 years, of which 2668 participants developed T2D. ROC curve analysis showed that TyG was the most robust predictor of 3-year [aera under the ROC (AUC) = 0.77, 95% CI: 0.768, 0.772] and 5-year T2D risk (AUC = 0.763, 95% CI: 0.760, 0.765). In addition, sensitivity analysis showed an association between TyG and an increased incidence of T2D. Conclusions The results suggest that TyG was a superior for predicting the risk of developing T2D in the general Chinese population.

Purpose Previous studies have shown higher cardiovascular mortality risk with higher monocyte–lymphocyte ratio levels in general population. However, the levels of oxidative stress in individuals with type 2 diabetes are higher than those in the general population, which may affect the link between monocyte‐to‐lymphocyte ratio and cardiovascular disease deaths. And the association between the monocyte‐to‐lymphocyte ratio and mortality risk in people with type 2 diabetes still be unknown. This study aimed to investigate the prognostic significance of monocyte‐to‐lymphocyte ratio in type 2 diabetes. Methods This analysis involved 2,954 individuals with type 2 diabetes from the National Health and Nutrition Examination Survey 1999–2010. The National Death Index records through December 31, 2019, was used to determine all‐cause and cardiovascular mortality. The prognostic roles were determined using Cox regression models, restricted cubic spline analysis, and time‐dependent receiver operating characteristic curve analysis. Results During an average follow‐up period of 12.4 years, a total of 1,007 deaths occurred, while 252 were due to cardiovascular disease. An elevated monocyte‐to‐lymphocyte ratio level exhibited a significant dose–response relationship with an increased risk of all‐cause mortality (1.34 [95% CI 1.12, 1.60] for all‐cause mortality [P trend = 0.001]). The multivariable‐adjusted HR was 1.81 (95% CI 1.25, 2.63) (P trend = 0.001) for cardiovascular mortality indicating a U‐shaped relationship (P nonlinear = 0.013). Conclusions The results of this study indicate a U‐shaped relationship between the monocyte‐to‐lymphocyte ratio and cardiovascular mortality in individuals with diabetes. Both very low and high monocyte‐to‐lymphocyte ratio monocyte‐to‐lymphocyte ratio values were found to be associated with increased cardiovascular mortality risk. The association between monocyte‐to‐lymphocyte ratio and cardiovascular mortality in type 2 diabetes show a U‐shaped relationship, which means that both very low or high MLR were associated with higher cardiovascular mortality.

Inflammation critically contributes to the development of various metabolic diseases. However, the effects of inhibiting inflammatory signaling on hepatic steatosis and insulin resistance, as well as the underlying mechanisms remain obscure. In the current study, male C57BL/6J mice were fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD-fed mice were respectively treated with p65 siRNA, non-silence control siRNA or vehicle every 4th day for the last 4 weeks. Vehicle-treated (HF) and non-silence siRNA-treated (HFNS) mice displayed overt inflammation, hepatic steatosis and insulin resistance compared with chow-diet-fed (NC) mice. Upon treatment with NF-κB p65 siRNA, HFD-fed (HFPS) mice were protected from hepatic steatosis and insulin resistance. Furthermore, Atg7 and Beclin1 expressions and p-AMPK were increased while p-mTOR was decreased in livers of HFPS mice in relative to HF and HFNS mice. These results suggest a crosslink between NF-κB signaling pathway and liver AMPK/mTOR/autophagy axis in the context of hepatic steatosis and insulin resistance.