The circadian syndrome is a predictor for cognition impairment in middle-aged adults: Comparison with the metabolic syndrome.

AIMS: Circadian syndrome (CircS) is considered a better predictor for cardiovascular disease than the metabolic syndrome (MetS). We aim to examine the associations between CircS and MetS with cognition in Chinese adults. METHOD: We used the data of 8546 Chinese adults aged ≥40 years from the 2011 China Health and Retirement Longitudinal Study. MetS was defined using harmonised criteria. CircS included the components of MetS plus short sleep and depression. The cut-off for CircS was set as ≥4. Global cognitive function was assessed during the face-to-face interview. RESULTS: CircS and MetS had opposite associations with the global cognition score and self-reported poor memory. Compared with individuals without the CircS and MetS, the regression coefficients (95%CI) for global cognition score were -1.02 (-1.71 to -0.34) for CircS alone and 0.52 (0.09 to 0.96) for MetS alone in men; -1.36 (-2.00 to -0.72) for CircS alone and 0.60 (0.15 to 1.06) for MetS alone in women. Having CircS alone was 2.53 times more likely to report poor memory in men (95%CI 1.80-3.55) and 2.08 times more likely in women (95%CI 1.54-2.81). In contrast, having MetS alone was less likely to report poor memory (OR 0.64 (0.49-0.84) in men and 0.65 (0.52-0.81) in women). People with CircS and MetS combined were more likely to have self-reported poor memory. CONCLUSIONS: CircS is a strong and better predictor for cognition impairment than MetS in Chinese middle-aged adults. MetS without short sleep and depression is associated with better cognition.

Moxonidine Increases Uptake of Oxidised Low-Density Lipoprotein in Cultured Vascular Smooth Muscle Cells and Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice.

This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II. The levels of circulating lipid hydroperoxides in mouse plasma were measured by ferrous oxidation-xylenol orange assay. Moxonidine administration increased oxidised LDL uptake by VSMCs via activation of α2 adrenoceptors. Moxonidine increased the expression of LDL receptors and the lipid efflux transporter ABCG1. Moxonidine inhibited mRNA expression of inflammatory genes and increased VSMC migration. Moxonidine administration to ApoE-/- mice (18 mg/kg/day) decreased atherosclerosis formation in the aortic arch and left common carotid artery, associated with increased plasma lipid hydroperoxide levels. In conclusion, moxonidine inhibited atherosclerosis in ApoE-/- mice, which was accompanied by an increase in oxidised LDL uptake by VSMCs, VSMC migration, ABCG1 expression in VSMCs and lipid hydroperoxide levels in the plasma.

Low- and middle-income countries demonstrate rapid growth of type 2 diabetes: an analysis based on Global Burden of Disease 1990-2019 data.

AIMS/HYPOTHESIS: The study aims to quantify the global trend of the disease burden of type 2 diabetes caused by various risks factors by country income tiers. METHODS: Data on type 2 diabetes, including mortality and disability-adjusted life years (DALYs) during 1990-2019, were obtained from the Global Burden of Disease Study 2019. We analysed mortality and DALY rates and the population attributable fraction (PAF) in various risk factors of type 2 diabetes by country income tiers. RESULTS: Globally, the age-standardised death rate (ASDR) attributable to type 2 diabetes increased from 16.7 (15.7, 17.5)/100,000 person-years in 1990 to 18.5 (17.2, 19.7)/100,000 person-years in 2019. Similarly, age-standardised DALY rates increased from 628.3 (537.2, 730.9)/100,000 person-years to 801.5 (670.6, 954.4)/100,000 person-years during 1990-2019. Lower-middle-income countries reported the largest increase in the average annual growth of ASDR (1.3%) and an age-standardised DALY rate (1.6%) of type 2 diabetes. The key PAF attributing to type 2 diabetes deaths/DALYs was high BMI in countries of all income tiers. With the exception of BMI, while in low- and lower-middle-income countries, risk factors attributable to type 2 diabetes-related deaths and DALYs are mostly environment-related, the risk factors in high-income countries are mostly lifestyle-related. CONCLUSIONS/INTERPRETATION: Type 2 diabetes disease burden increased globally, but low- and middle-income countries showed the highest growth rate. A high BMI level remained the key contributing factor in all income tiers, but environmental and lifestyle-related factors contributed differently across income tiers. DATA AVAILABILITY: To download the data used in these analyses, please visit the Global Health Data Exchange at http://ghdx.healthdata.org/gbd-2019 .

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD. RESULTS: There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD. CONCLUSION: Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.HighlightsWhat is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

Addition of glomerular lesion severity improves the value of anemia status for the prediction of renal outcomes in Chinese patients with type 2 diabetes.

We aimed to determine the utility of biopsy data and anemia for the prediction of renal outcomes in Chinese patients with type 2 diabetes. In total, 441 Chinese patients with type 2 diabetes and biopsy-confirmed diabetic nephropathy (DN) were enrolled in a retrospective study. Their renal pathology was assessed using the Renal Pathology Society system. Cox proportional hazards models were used to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), and immunofluorescence staining was used to assess the expression of hypoxia-inducible factor (HIF)-α in patients' kidneys. We found that glomerular pathology classification was an independent pathological predictor of low hemoglobin concentration, according to linear and logistic regression analyses. Each 1 g/dL decrease in baseline hemoglobin concentration was associated with a 42% higher risk of an adverse renal outcome, after adjustment for clinical and pathologic covariates. In patients with severe glomerular lesions, the risk of progression to ESRD was significantly higher if mild or moderate/severe anemia was present, but in patients with mild glomerular lesions, the risk was only significantly higher in those with moderate or severe anemia than in the absence of anemia. Harrell's C Concordance was improved, but the Akaike information criterion was worsened by adding the glomerular pathology classification to the use of anemia status and clinical data. Immunofluorescence staining revealed that renal HIF-1α and HIF-2α expression was significantly higher in classes II-IV than class I. Thus, the addition of glomerular pathology classification increases the value of anemia status for the prediction of the progression to ESRD.

How to inhibit transforming growth factor beta safely in diabetic kidney disease.

PURPOSE OF REVIEW: Diabetic kidney disease (DKD) is a leading cause of mortality and morbidity in diabetes. This review aims to discuss the major features of DKD, to identify the difficult barrier encountered in developing a therapeutic strategy and to provide a potentially superior novel approach to retard DKD. RECENT FINDINGS: Renal inflammation and fibrosis are prominent features of DKD. Transforming growth factor beta (TGFß) with its activity enhanced in DKD plays a key pathological profibrotic role in promoting renal fibrosis. However, TGFß is a difficult drug target because it has multiple important physiological functions, such as immunomodulation. These physiological functions of TGFß can be interrupted as a result of complete blockade of the TGFß pathway if TGFß is directly targeted, leading to catastrophic side-effects, such as fulminant inflammation. Cell division autoantigen 1 (CDA1) is recently identified as an enhancer of profibrotic TGFß signaling and inhibitor of anti-inflammatory SIRT1. Renal CDA1 expression is elevated in human DKD as well as in rodent models of DKD. Targeting CDA1, by either genetic approach or pharmacological approach in mice, leads to concurrent attenuation of renal fibrosis and inflammation without any deleterious effects observed. SUMMARY: Targeting CDA1, instead of directly targeting TGFß, represents a superior approach to retard DKD.

Genetic deletion of a short fragment of glucokinase in rabbit by CRISPR/Cas9 leading to hyperglycemia and other typical features seen in MODY-2.

Glucokinase (GCK) is a key enzyme in glucose sensing and glycemic regulation. In humans, mutations in the GCK gene cause maturity-onset diabetes of the young 2 (MODY-2), a disease that is characterized by an early-onset and persistent hyperglycemia. It is known that Gck knockout (KO) is lethal in mice with Gck KO mice dying within 2 weeks after birth. Therefore, Gck KO mice are not suitable for preclinical study and have limited suitability to study the pathophysiological role of glucokinase in vivo. Here, we report the generation of a novel rabbit with a non-frameshift mutation of GCK gene (GCK-NFS) by cytoplasm microinjection of Cas9 mRNA and gRNA. These GCK-NFS rabbits showed typical features of MODY-2 including hyperglycemia and glucose intolerance with similar survival rate and weight compared to wild-type (WT) rabbits. The diabetic phenotype including pancreatic and renal dysfunction was also found in the F1-generation rabbits, indicating that the genetic modification is germline transmissible. Treatment of GCK-NFS rabbit with glimepiride successfully reduced the fasting blood glucose drastically and improved its islet function. In conclusion, this novel GCK mutant rabbit generated with the CRISPR/Cas9 system mimics most, if not all, histopathological and functional defects seen in MODY-2 patients such as hyperglycemia and will be a valuable rabbit model for preclinical studies and drug screening for diabetes as well as for studying the pathophysiological role of glucokinase.

Transforming growth factor ß (TGFß) and related molecules in chronic kidney disease (CKD).

The incidence of chronic kidney diseases (CKDs) is expected to rise, fuelled by the ever increasing epidemic of Type 2 diabetes. Despite extensive research in this area, there are currently no effective treatments available to sufficiently halt the progression of CKD towards renal failure. This is largely due to ongoing secondary pathological processes generally elicited by the onset of disease. Fibrosis, in particular, is a prominent pathological hallmark of many forms of CKD and considered to be a central contributing factor for the progression of CKD towards end-stage renal disease. Transforming growth factor ß (TGFß) has been implicated to be a major regulatory cytokine in CKD, especially in fibrosis development, and reduced TGFß signalling activity has been previously shown to be associated with improved renal outcomes in experimental animal studies. A number of molecules related to and/or interacting with the TGFß signalling pathway have been identified as potential therapeutic targets. However, due to its pleiotropic nature, complete inhibition of the TGFß signalling pathway is likely to lead to deleterious side effects. Therefore, a better understanding of this pathway and the molecules modulating this pathway is necessary to develop more efficacious and therapeutic strategies to combat progression of CKD.

Ultrasound Combined with Microbubbles Enhances the Effects of Methylprednisolone in Lipopolysaccharide-Induced Human Mesangial Cells.

A novel drug delivery system mediated by ultrasound (US) combined with microbubbles (MBs) (US+MB) could improve local drug concentration to enhance its efficacy. To investigate the influence of US+MB on methylprednisolone (MP), the effect of US+MB combined with MP (US+MB+MP) on lipopolysaccharide (LPS)-induced human mesangial cells (HMCs) and the underlying mechanism were explored in this study. The results revealed that HMCs treated with LPS underwent significant proliferation and exhibited an increase in nuclear transcription factor-κB (NF-κB) and transforming growth factor-ß1 (TGF-ß1) expression and a decrease in cellular apoptosis. This effect was significantly inhibited by MP (30-100 µg/ml), US combined with MBs (3.22 × 107 and 8.05 × 107 bubbles/ml), and US combined with both MBs (1.29 × 107 bubbles/ml) and MP (12 µg/ml) (US+MB1+MP12). The effect of US+MB1+MP12 was better than the effect of 12 µg/ml of MP alone and was similar to the effect of 100 µg/ml of MP. Additionally, the intracellular free MP content was significantly higher in the US+MB1+MP12 group than in the MP12 group. US combined with MBs not only inhibited LPS-induced HMC proliferation and NF-κB and TGF-ß1 expression and increased cellular apoptosis but also synergized with the pharmacologic effect of MP. The mechanism is partially due to the US-assisted MB local drug delivery and the anti-inflammatory effect induced by US combined with MBs.

Genetic deletion of cell division autoantigen 1 retards diabetes-associated renal injury.

Cell division autoantigen 1 (CDA1) enhances TGF-ß signaling in renal and vascular cells, and renal expression of CDA1 is elevated in animal models of diabetes. In this study, we investigated the genetic deletion of Tspyl2, the gene encoding CDA1, in C57BL6 and ApoE knockout mice. The increased renal expression of TGF-ß1, TGF-ß type I and II receptors, and phosphorylated Smad3 associated with diabetes in wild-type mice was attenuated in diabetic CDA1 knockout mice. Notably, CDA1 deletion significantly reduced diabetes-associated renal matrix accumulation and immunohistochemical staining for collagens III and IV and attenuated glomerular and tubulointerstitial injury indices, despite the presence of persistent hyperglycemia, polyuria, renal hypertrophy, and hyperfiltration. Furthermore, CDA1 deletion reduced gene expression of TGF-ß1 receptors in the kidney, resulting in a functionally attenuated response to exogenous TGF-ß, including reduced levels of phosphorylated Smad3 and ERK1/2, in primary kidney cells from CDA1 knockout animals. Taken together, these data suggest that CDA1 deletion reduces but does not block renal TGF-ß signaling. Because direct antagonism of TGF-ß or its receptors has unwanted effects, CDA1 may be a potential therapeutic target for retarding DN and perhaps, other kidney diseases associated with TGF-ß-mediated fibrogenesis.

Projected rapid growth in diabetes disease burden and economic burden in China: a spatio-temporal study from 2020 to 2030.

Background: This study projects the trend of disease burden and economic burden of diabetes in 33 Chinese provinces and nationally during 2020-2030 and investigates its spatial disparities. Methods: Time series prediction on the prevalence and disability-adjusted life-year (DALY) rates of diabetes was conducted using a Bayesian modelling approach in 2020-2030. The top-down method and the human capital method were used to predict the direct and indirect costs of diabetes for each Chinese province. Global and local spatial autocorrelation analyses were used to identify geographic clusters of low-or high-burden areas. Findings: Diabetes prevalence in Chinese adults aged 20-79 years was projected to increase from 8.2% to 9.7% during 2020-2030. During the same period, the total costs of diabetes would increase from $250.2 billion to $460.4 billion, corresponding to an annual growth rate of 6.32%. The total costs of diabetes as a percentage of GDP would increase from 1.58% to 1.69% in China during 2020-2030, suggesting a faster growth in the economic burden of diabetes than China's economic growth. Consistently, the per-capita economic burden of diabetes would increase from $231 to $414 in China during 2020-2030, with an annual growth rate of 6.02%. High disease and economic burden areas were aggregated in Northeast and/or North China. Interpretation: Our study projects a significant growth of disease and economic burden of diabetes in China during 2020-2030, with strong spatial aggregation in northern Chinese regions. The increase in the economic burden of diabetes will exceed that of GDP. Funding: National Natural Science Foundation of China, Outstanding Young Scholars Funding.

Association between Covid-19 vaccination and incidence of type 1 diabetes in China: Evidence from 14.14 million registered residents between 2007 and 2021.

AIMS: Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where>90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021. METHODS: A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center. Annual incidence rates were calculated by age group and gender, and annual percentage changes were assessed using Joinpoint regression. RESULTS: The study included 14.14 million registered residents, and 7,697 people with newly diagnosed T1D were identified from 2007 to 2021. T1D incidence increased from 2.77 in 2007 to 3.84 per 100,000 persons in 2021. However, T1D incidence was stable from 2019 to 2021, and the incidence rate did not increase when people were vaccinated in January-December 2021. The incidence of FT1D did not increase from 2015 to 2021. CONCLUSIONS: The findings suggest that COVID-19 vaccination did not increase the onset of T1D or have a significant impact on T1D pathogenesis, at least not on a large scale.

Global Diabetes Prevalence in COVID-19 Patients and Contribution to COVID-19- Related Severity and Mortality: A Systematic Review and Meta-analysis.

BACKGROUND: COVID-19 and diabetes both contribute to large global disease burdens. PURPOSE: To quantify the prevalence of diabetes in various COVID-19 disease stages and calculate the population attributable fraction (PAF) of diabetes to COVID-19-related severity and mortality. DATA SOURCES: Systematic review identified 729 studies with 29,874,938 COVID-19 patients. STUDY SELECTION: Studies detailed the prevalence of diabetes in subjects with known COVID-19 diagnosis and severity. DATA EXTRACTION: Study information, COVID-19 disease stages, and diabetes prevalence were extracted. DATA SYNTHESIS: The pooled prevalence of diabetes in stratified COVID-19 groups was 14.7% (95% CI 12.5-16.9) among confirmed cases, 10.4% (7.6-13.6) among nonhospitalized cases, 21.4% (20.4-22.5) among hospitalized cases, 11.9% (10.2-13.7) among nonsevere cases, 28.9% (27.0-30.8) among severe cases, and 34.6% (32.8-36.5) among deceased individuals, respectively. Multivariate metaregression analysis explained 53-83% heterogeneity of the pooled prevalence. Based on a modified version of the comparative risk assessment model, we estimated that the overall PAF of diabetes was 9.5% (7.3-11.7) for the presence of severe disease in COVID-19-infected individuals and 16.8% (14.8-18.8) for COVID-19-related deaths. Subgroup analyses demonstrated that countries with high income levels, high health care access and quality index, and low diabetes disease burden had lower PAF of diabetes contributing to COVID-19 severity and death. LIMITATIONS: Most studies had a high risk of bias. CONCLUSIONS: The prevalence of diabetes increases with COVID-19 severity, and diabetes accounts for 9.5% of severe COVID-19 cases and 16.8% of deaths, with disparities according to country income, health care access and quality index, and diabetes disease burden.

Renal fibrosis as a hallmark of diabetic kidney disease: potential role of targeting transforming growth factor-beta (TGF-ß) and related molecules.

INTRODUCTION: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) worldwide. Currently, there is no effective treatment to completely prevent DKD progression to ESRD. Renal fibrosis and inflammation are the major pathological features of DKD, being pursued as potential therapeutic targets for DKD. AREAS COVERED: Inflammation and renal fibrosis are involved in the pathogenesis of DKD. Anti-inflammatory drugs have been developed to combat DKD but without efficacy demonstrated. Thus, we have focused on the mechanisms of TGF-ß-induced renal fibrosis in DKD, as well as discussing the important molecules influencing the TGF-ß signaling pathway and their potential development into new pharmacotherapies, rather than targeting the ligand TGF-ß and/or its receptors, such options include Smads, microRNAs, histone deacetylases, connective tissue growth factor, bone morphogenetic protein 7, hepatocyte growth factor, and cell division autoantigen 1. EXPERT OPINION: TGF-ß is a critical driver of renal fibrosis in DKD. Molecules that modulate TGF-ß signaling rather than TGF-ß itself are potentially superior targets to safely combat DKD. A comprehensive elucidation of the pathogenesis of DKD is important, which requires a better model system and access to clinical samples via collaboration between basic and clinical researchers.

The Circadian Syndrome Is a Significant and Stronger Predictor for Cardiovascular Disease than the Metabolic Syndrome-The NHANES Survey during 2005-2016.

The study aimed to compare the predictive value of the Circadian Syndrome (CircS) and Metabolic Syndrome (MetS) for cardiovascular disease (CVD). We used data of 12,156 adults aged ≥20 years who attended National Health and Nutrition Examination Survey (NHANES) 2005-2016. Mortality was obtained from the registry updated to 2019. The CircS was defined based on components of the MetS, in addition to short sleep and depression. Both the MetS and CircS were directly associated with self-reported history of CVD. The odds ratios for prevalent CVD associated with the CircS and MetS, respectively, were 2.92 (95% confidence interval (CI) 2.21-3.86) and 3.20 (2.38-4.30) in men, and 3.27 (2.34-4.59) and 3.04 (2.15-4.30) in women. The CircS had a better predictive power for prevalent CVD than that of MetS, as indicated by the higher positive predictive value (PPV); in men, the PPV for prevalent CVD with CircS was 23.1% and with MetS 20.9%, and in women these were 17.9% vs. 16.4%, respectively. However, the PPV of the CircS and MetS did not differ for the CVD mortality prediction. Women with CircS alone had a higher risk for both prevalent CVD and CVD mortality than those with MetS alone. In conclusion, the CircS is a significant and stronger predictor for CVD than the MetS in US adults.

New-onset COVID-19-related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection.

Objective: The pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19. Methods: Fasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death. Results: A total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet. Conclusions: New-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

Elevated Fasting Blood Glucose Levels Are Associated with Worse Clinical Outcomes in COVID-19 Patients Than in Pneumonia Patients with Bacterial Infections.

Aims: We investigate how fasting blood glucose (FBG) levels affect the clinical severity in coronavirus disease 2019 (COVID-19) patients, pneumonia patients with sole bacterial infection, and pneumonia patients with concurrent bacterial and fungal infections. Methods: We enrolled 2761 COVID-19 patients, 1686 pneumonia patients with bacterial infections, and 2035 pneumonia patients with concurrent infections. We used multivariate logistic regression analysis to assess the associations between FBG levels and clinical severity. Results: FBG levels in COVID-19 patients were significantly higher than in other pneumonia patients during hospitalisation and at discharge (all p < 0.05). Among COVID-19 patients, the odds ratios of acute respiratory distress syndrome (ARDS), respiratory failure (RF), acute hepatitis/liver failure (AH/LF), length of stay, and intensive care unit (ICU) admission were 12.80 (95% CI, 4.80−37.96), 5.72 (2.95−11.06), 2.60 (1.20−5.32), 1.42 (1.26−1.59), and 5.16 (3.26−8.17) times higher in the FBG ≥7.0 mmol/L group than in FBG < 6.1 mmol/L group, respectively. The odds ratios of RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with sole bacterial infection (3.70 [2.21−6.29]; 1.56 [1.17−2.07]; 0.98 [0.88−1.11]; 2.06 [1.26−3.36], respectively). The odds ratios of ARDS, RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with concurrent infections (3.04 [0.36−6.41]; 2.31 [1.76−3.05]; 1.21 [0.97−1.52]; 1.02 [0.93−1.13]; 1.72 [1.19−2.50], respectively). Among COVID-19 patients, the incidence rate of ICU admission on day 21 in the FBG ≥ 7.0 mmol/L group was six times higher than in the FBG < 6.1 mmol/L group (12.30% vs. 2.21%, p < 0.001). Among other pneumonia patients, the incidence rate of ICU admission on day 21 was only two times higher. Conclusions: Elevated FBG levels at admission predict subsequent clinical severity in all pneumonia patients regardless of the underlying pathogens, but COVID-19 patients are more sensitive to FBG levels, and suffer more severe clinical complications than other pneumonia patients.

Whether Renal Pathology Is an Independent Predictor for End-Stage Renal Disease in Diabetic Kidney Disease Patients with Nephrotic Range Proteinuria: A Biopsy-Based Study.

Aims: To investigate whether renal pathology is an independent predictor for end-stage renal disease (ESRD) in diabetic kidney diseases (DKD) with nephrotic range proteinuria. Methods: A total of 199 DKD patients with nephrotic range proteinuria underwent renal biopsy and were divided into an ESRD group and a non-ESRD group. A Kaplan−Meier analysis was used to compare renal survival rate, and univariate and multivariate Cox proportional hazard analyses were used to determine the predictors of the ESRD. Results: The mean age of included patients was 51.49 ± 9.12 years and 113 patients (56.8%) progressed to ESRD. The median follow-up period was 16 (12−28) months. The glomerular pathology class III is the most common type (54.3%). In the Kaplan−Meier analysis, compared with patients without ESRD, patients with ESRD had a longer duration of diabetes (≥6 years), lower eGFR (<60 mL/min/1.73 m2), lower albumin (<30 g/L), lower hemoglobin (<120 g/L), and a higher grade of glomerular stage (class III + IV vs. class I + II) (p < 0.05). The hemoglobin and e-GFR, but not the histopathological damage, were significantly associated with a higher risk of ESRD in both the univariate and multivariate Cox analyses. Conclusions: In patients with diabetic kidney disease characterized by nephrotic range proteinuria, histopathological damage (glomerular alterations, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation, and arteriolar hyalinosis) is not associated with poor renal outcomes, but hemoglobin and e-GFR could predict poor renal outcomes.

Prognostic value of metabolic syndrome in renal structural changes in type 2 diabetes.

PURPOSE: To investigate the prognostic value of metabolic syndrome (MetS) and its relationship with renal structure changes in patients with type 2 diabetes and associated diabetic nephropathy (DN). METHODS: 411 Chinese patients with type 2 diabetes and biopsy-confirmed DN were enrolled in this retrospective study. MetS was defined according to the modified criteria of the 2005 International Diabetes Federation. Baseline demographics and clinical information at the time of renal biopsy were extracted from the hospital's electronic medical records system. Renal pathological findings were assessed according to Renal Pathology Society system. Univariate and multivariate logistic regression analyses were performed to define the pathological covariates associated with MetS. A competing risk model, with death as the competing risk, was used to estimate the sub-distribution hazard ratio (SHR) of MetS for end-stage kidney disease (ESKD). RESULTS: 224 (55%) patients had MetS. Patients with MetS had poor renal function and more severe interstitial fibrosis tubular atrophy scores (IFTA) than those without MetS. Multivariate logistic regression analysis revealed that IFTA was significantly associated with MetS (odds ratio per score increase 1.45, 95% confidence interval [CI] 1.02-2.05). Of the patients with DN at risk, 40% of patients progressed to ESKD. After adjusting for renal function and pathological parameters, the presence of MetS was an independent predictor for progression to ESKD (SHR 1.93, 95% CI 1.34-2.79). The SHRs for progression to ESKD also increased as the number of MetS components increased. Additionally, adding the IFTA scores improved the prognostic power of a model that only contained MetS and clinical covariates for predicting future ESKD. CONCLUSION: MetS is an independent prognostic predictor of ESKD in patients with T2D and DN, while adding the IFTA scores increased the prognostic value of MetS for renal outcome.