The triglyceride glucose index as a sensitive predictor for the risk of MACCEs in patients with diabetic foot ulcers: An ambispective longitudinal cohort study.

The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.

Characteristics of metabolic inflammatory syndrome among inpatients with type 2 diabetes: A cross-sectional study in China.

BACKGROUND: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China. METHODS: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis. RESULTS: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787). CONCLUSIONS: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.

The clinical value of glycosylated hemoglobin level in newly diagnosed ketosis-prone type 2 diabetes.

Objective: To evaluate the clinical value of glycosylated hemoglobin (HbA1c) in newly diagnosed ketosis-prone type 2 diabetes (KPD). Methods: A total of 330 patients with newly diagnosed type 2 diabetes (T2DM) hospitalized in our department with an average age of 48.72 ± 13.07 years old were selected and divided into T2DM group (193 cases) and KPD group (137 cases) according to whether they were combined with ketosis. According to the quartile level of HbA1c, they were divided into group A (HbA1c < 8.90%, 84 cases), group B (8.90%≤HbA1c < 10.70%, 86 cases), group C (10.70%≤HbA1c ≤ 12.40%, 85 cases) and group D (HbA1c > 12.40%, 75 cases). The general clinical features, laboratory indicators and islet function of each group were compared. Spearman correlation analysis was used to explore the correlation between HbA1c and ß- Hydroxybutyric acid (ß- HB) and islet function. ROC curve was used to analyze the sensitivity and specificity of HbA1c in diagnosing KPD, and the optimal tangent point was obtained. Results: HbA1c, ß-HB, FFA, RBG, insulin dosage, GSP, OGTT (0, 0.5, 1, 2, 3h) in KPD group were significantly higher than those in T2DM group (P< 0.001). HDL-C, IRT (0, 0.5, 1, 2, 3h), HOMA-ß, HOMA-IR, HOMA-IS, ΔC30/ΔG30, AUC insulin were significantly lower than those in T2DM group (P< 0.001). With the increase of HbA1c level, the incidence of ketosis, ß-HB, FFA and insulin dosage increased, while IRT (0, 0.5, 1, 2, 3h), ΔC30/ΔG30, AUC insulin, HOMA-ß and HOMA-IS decreased accordingly (P< 0.001). In all newly diagnosed T2DM patients, Spearman correlation analysis showed that HbA1c was positively correlated with ß-HB (r=0.539, P < 0.001), and was negatively correlated with HOMA-ß (r=-0.564, P < 0.001), HOMA-IS (r=-0.517, P < 0.01, P < 0.001), HOMA-IR (r=-0.177, P < 0.001), ΔC30/ΔG30 (r=-0.427, P < 0.01) and AUC insulin (r=-0.581, P < 0.001). In ROC curve analysis, the optimal threshold for the diagnosis of KPD was 10.15%, Youden index was 0.616, area under the curve (AUC) was 0.882, sensitivity = 92.70%, specificity = 70.50%. Conclusion: In newly diagnosed T2DM patients, if HbA1c > 10.15%, it is more likely to develop KPD. Monitoring HbA1c level is conducive to timely detection of high-risk individuals with KPD and taking appropriate measures to prevent the occurrence and development of the disease.

PP2Ac knockdown attenuates lipotoxicity­induced pancreatic ß­cell dysfunction and apoptosis.

Protein phosphatase 2A (PP2A) is one of the most common serine/threonine phosphatases in mammalian cells, and it primarily functions to regulate cell signaling, glycolipid metabolism and apoptosis. The catalytic subunit of PP2A (PP2Ac) plays an important role in the functions of the protein. However, there are few reports on the regulatory role of PP2Ac in pancreatic ß-cells under lipotoxic conditions. In the present study, mouse insulinoma 6 (MIN6) pancreatic cells were transfected with short hairpin RNAs to generate PP2Ac knockdown cells and incubated with palmitate (PA) to establish a lipotoxicity model. Serine/threonine phosphatase assay system, Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay and western blotting were used to measure PP2A activity, cell viability, apoptosis, oxidative stress and insulin secretion in the cells. In addition, a mouse model of lipotoxicity was established with a high-fat diet (HFD) and the knockdown of PP2Ac using adeno-associated viruses to interfere with PP2Ac expression in the pancreatic tissues. The activity of PP2A in the mouse pancreatic tissue and the serum insulin level were measured. Furthermore, the proliferation of mouse pancreatic ß-cells was assessed using pancreatic tissue immunofluorescence. PP2Ac knockdown inhibited lipotoxicity-induced PP2A hyperactivation, increased the resistance of pancreatic ß-cells to lipotoxicity and attenuated PA-induced apoptosis in MIN6 cells. It also protected the endoplasmic reticulum and mitochondria, and ameliorated insulin secretion. The results of mRNA sequencing and western blotting analysis suggested that the protective effects of PP2Ac knockdown in MIN6 cells may be mediated via the MAPK pathway. Moreover, the results of the animal experiments suggested that specific knockdown of pancreatic PP2Ac effectively attenuated HFD-induced insulin resistance and reduced the compensatory proliferation of pancreatic ß-cells in mice. In summary, the present study revealed the effects of interfering with PP2Ac gene expression on pancreatic ß-cells in vivo and in vitro and the underlying mechanisms, which may provide insights for the treatment of type 2 diabetes mellitus in the clinic.

Poricoic acid A induces mitophagy to ameliorate podocyte injury in diabetic kidney disease via downregulating FUNDC1.

Diabetic kidney disease (DKD) is a devastating complication of diabetes mellitus (DM) and is the most prevalent chronic kidney disease (CKD). Poricoic acid A (PAA), a component isolated from Traditional Chinese Medicine (TCM) Poria cocos, has hypoglycaemic and anti-fibrosis effects. However, the role of PAA in DKD remains largely unclear. To mimics an in vitro model of DKD, the mouse podocyte MPC5 cells were treated with high glucose (25 mM; HG) for 24 h. CCK-8 and flow cytometry assays were conducted for assessing MPC5 cell viability and apoptosis. Meanwhile, streptozotocin (STZ) was used to induce experimental DKD in mice by intraperitoneal injection. PAA notably inhibited the apoptosis and inflammation, reduced the generation of ROS, and elevated the MMP level in HG-treated MPC5 cells. Moreover, PAA obviously reduced blood glucose and urine protein levels, inhibited renal fibrosis in DKD mice. Meanwhile, PAA markedly increased LC3 and ATG5 levels and declined p62 and FUNDC1 levels in HG-treated MPC5 cells and in the kidney tissues of DKD mice, leading to the activation of cell mitophagy. Furthermore, the downregulation of FUNDC1 also inhibited apoptosis, inflammation, and promoted mitophagy in HG-treated MPC5 cells. As expected, the knockdown of FUNDC1 further enhanced the protective role of PAA in MPC5 cells following HG treatment, indicating that induction of mitophagy could attenuate podocyte injury. Collectively, PAA could exert beneficial effects on podocyte injury in DKD by promoting mitophagy via downregulating FUNDC1. These findings suggested that PAA may have great potential in alleviating kidney injury in DKD.

Cancer-cell-secreted miR-204-5p induces leptin signalling pathway in white adipose tissue to promote cancer-associated cachexia.

Cancer-associated cachexia is a multi-organ weight loss syndrome, especially with a wasting disorder of adipose tissue and skeletal muscle. Small extracellular vesicles (sEVs) serve as emerging messengers to connect primary tumour and metabolic organs to exert systemic regulation. However, whether and how tumour-derived sEVs regulate white adipose tissue (WAT) browning and fat loss is poorly defined. Here, we report breast cancer cell-secreted exosomal miR-204-5p induces hypoxia-inducible factor 1A (HIF1A) in WAT by targeting von Hippel-Lindau (VHL) gene. Elevated HIF1A protein induces the leptin signalling pathway and thereby enhances lipolysis in WAT. Additionally, exogenous VHL expression blocks the effect of exosomal miR-204-5p on WAT browning. Reduced plasma phosphatidyl ethanolamine level is detected in mice lack of cancer-derived miR-204-5p secretion in vivo. Collectively, our study reveals circulating miR-204-5p induces hypoxia-mediated leptin signalling pathway to promote lipolysis and WAT browning, shedding light on both preventive screenings and early intervention for cancer-associated cachexia.

FUNDC1 modulates mitochondrial defects and pancreatic ß-cell dysfunction under lipotoxicity.

Insulin resistance and many metabolic disorders are causally linked to mitochondrial dysfunction or defective mitochondrial quality control. Mitophagy is a highly selective mechanism that recognizes and removes damaged mitochondria to maintain mitochondrial homeostasis. Here, we addressed the potential role of FUNDC1, a mediator of mitophagy, in pancreatic ß-cell dysfunction under lipotoxicity. In pancreatic MIN6 cells, FUNDC1 deficiency aggravated palmitate-induced mitochondrial dysfunction, which led to cell death and insulin insensitivity. Interestingly, FUNDC1 overexpression prevented these cellular harms brought on by palmitate. In mice models, pancreatic-specific FUNDC1 overexpression alleviated high-fat diet (HFD)-induced insulin resistance and obesity. Mechanistically, pancreatic-specific overexpression of FUNDC1 ameliorated mitochondrial defects and endoplasmic reticulum (ER) stress upon HFD. Our research indicates that FUNDC1 plays an essential role in apoptosis and dysfunction of pancreatic ß-cells via modulating lipotoxicity-induced mitochondrial defects.

Hepatic IDH2 regulates glycolysis and gluconeogenesis.

BACKGROUND AND AIMS: The liver plays a central role in controlling glucose and lipid metabolism. IDH2, a mitochondrial protein, controls TCA cycle flux. However, its role in regulating metabolism in obesity is still unclear. This study intends to investigate the impact of hepatic IDH2 expression on overnutrition-regulated glucose and lipid metabolism. METHODS: Hepatic IDH2 was knocked-out in mice by the approach of CRISPR-Cas9. Mice were subjected to starvation and refeeding for hepatic glucose and lipid studies in vivo. Primary hepatocytes and mouse normal liver cell line, AML12 cells were used for experiments in vitro. RESULTS: This study found that IDH2 protein levels were elevated in the livers of obese people and mice with high-fat diet consumption or hepatic steatosis. Liver IDH2-deletion mice (IDH2LKO) were resistant to high-fat diet-induced body weight gain, with lower serum glucose and TG levels, increased insulin sensitivity, and higher FGF21 secretion, despite the higher TG content in the liver. Consistently, overexpression of IDH2 in hepatocytes promoted gluconeogenesis and enhanced glycogenesis. By performing mass spectrometry and proteomics analyses, we further demonstrated that IDH2-deficiency in hepatocytes accelerated ATP production by increasing forward TCA cycle flux, thus promoting glycolysis pathway and decreasing glycogen synthesis at refeeding state, and inhibiting hepatic gluconeogenesis, increasing ß-oxidation during starvation. Moreover, experiments in vivo demonstrated that IDH2-knockout might not exacerbate hepatic inflammatory responses in the NASH model. CONCLUSIONS: Elevated hepatic IDH2 under over-nutrition state contributes to elevated gluconeogenesis and glycogen synthesis. Inhibition of IDH2 in the liver could be a potential therapeutic target for obesity and diabetes.

Development and validation of a nomogram for evaluating the incident risk of carotid atherosclerosis in patients with type 2 diabetes.

Introduction: The purpose of this study was to evaluate the clinical characteristics of carotid atherosclerotic disease in patients with type 2 diabetes mellitus, investigate its risk factors, and develop and validate an easy-to-use nomogram. Methods: 1049 patients diagnosed with type 2 diabetes were enrolled and randomly assigned to the training and validation cohorts. Multivariate logistic regression analysis identified independent risk factors. A method combining least absolute shrinkage and selection operator with 10-fold cross-validation was used to screen for characteristic variables associated with carotid atherosclerosis. A nomogram was used to visually display the risk prediction model. Nomogram performance was evaluated using the C index, the area under the receiver operating characteristic curve, and calibration curves. Clinical utility was assessed by decision curve analysis. Results: Age, nonalcoholic fatty liver disease, and OGTT3H were independent risk factors associated with carotid atherosclerosis in patients with diabetes. Age, nonalcoholic fatty liver disease, smoke, HDL-C, and LDL-C were characteristic variables used to develop the nomogram. The area under the curve for the discriminative power of the nomogram was 0.763 for the training cohort and 0.717 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the decision curve analysis indicated that the nomograms were clinically useful. Discussion: A new nomogram was developed and validated for assessing the incident risk of carotid atherosclerotic in patients with diabetes; this nomogram may act as a clinical tool to assist clinicians in making treatment recommendations.

Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes.

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.

Sigma­1 receptor overexpression promotes proliferation and ameliorates cell apoptosis in ß­cells.

Sigma­1 receptor (Sig­1R) is a class of orphan receptors, the potential role of which in pancreatic islet cells remains poorly understood. The present study aimed to investigate the role of Sig­1R in islet ß­cell proliferation and examine the effects of Sig­1R on islet ß­cell injury under lipotoxic conditions. Sig­1R­overexpressing MIN6 cells were generated by lentiviral vector transfection. The effect of Sig­1R overexpression on cell proliferation detected by EdU staining, cell cycle progression by propidium iodide (PI), apoptosis by Annexin V­APC/PI, mitochondrial membrane potential by Mitolite Red and cytoplasmic Ca2+ levelsby Fura­2/AM in islet ß­cells were measured by flow cytometry. Western blot analysis was used to measure protein expression levels of endoplasmic reticulum (ER) stress markers glucose­regulated protein 78 and C/EBP homologous protein, mitochondrial apoptotic proteins Bcl­2­associated X and Bcl­2 and cytochrome c. In addition, ATP levels and insulin secretion were separately measured using ATP Assay and mouse insulin ELISA. Mitochondria­associated ER membrane (MAM) structures in MIN6 cells were then detected using transmission electron microscopy. Protein disulfide isomerase expression and possible colocalization between inositol 1,4,5­trisphosphate receptor and voltage­dependent anion channel 1 were examined using immunofluorescence. Sig­1R overexpression was found to promote ß­cell proliferation by accelerating cell cycle progression. Furthermore, Sig­1R overexpression ameliorated the apoptosis rate whilst impairing insulin secretion induced by palmitic acid by relieving ER stress and mitochondrial dysfunction in MIN6 cells. Sig­1R overexpression also promoted Ca2+ transport between mitochondria and ER by increasing the quantity of ER adjacent to mitochondria in the 50­nm range. It was concluded that Sig­1R overexpression conferred protective effects on ß­cells against lipotoxicity as a result of the promotion of cell proliferation and inhibition of ER stress and oxidative stress, by regulating the structure of MAM.

RNF6 Targeted by miR-26a-5p Protects Pancreatic ß-Cell Function Against Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is characterized by progressive ß-cell dysfunction. Regulatory microRNAs (miRNAs) may be associated with this. METHODS: Serum miR-26a-5p and RNF6 levels were detected in T2D patients and healthy volunteers via qRT-PCR. Subsequently, the role of specific dysregulated miR-26a-5p or RNF6 in regulating insulin content, cell proliferation, and apoptosis was studied in INS-1 cells. The targeting correlation between miR-26a-5p and RNF6 was detected using a luciferase assay. RESULTS: RNF6 expression was significantly decreased in T2D individuals and INS-1 cells treated with high glucose, while miR-26a-5p expression was increased. In INS-1 cells, RNF6 overexpression or miR-26a-5p downregulation significantly increased insulin content and secretion, induced proliferation, and inhibited apoptosis. RNF6 has been identified as an miR-26a-5p target, which negatively regulates RNF6 to worsen INS-1 cell function. CONCLUSION: RNF6 promoted insulin secretion and induced cell proliferation in INS-1 cells. This may be related to miR-26a-5p targeting and negatively regulating T2D pathogenesis.

Case report: Diabetic muscle infarction with diabetic ketoacidosis: A rare complication of diabetes.

Background: Diabetic muscle infarction (DMI), which is also referred to as diabetic myonecrosis, is a rare and long-term complication of poorly controlled diabetes mellitus, while we found that acute diabetes decompensation, such as diabetic ketoacidosis (DKA), could also stimulate the occurrence and development of DMI. Case presentation: A 23-year-old woman with type 1 diabetes presented with a 10-day history of nausea, vomiting, pain, and swelling of her left leg. Her urine ketone test was positive. The 3-beta-hydroxybutyrate and leukocyte counts and creatine kinase levels were elevated. Magnetic resonance imaging of the left thigh revealed extensive deep tissue oedema and an increase in the T2 signal in the involved muscles. Once the diagnosis of DMI was made, she was managed with rest, celecoxib, clopidogrel and aggressive insulin therapy. Three months after treatment, the patient reported complete resolution of symptoms. Conclusion: DMI is a rare DM complication with a high recurrence rate, commonly presenting with chronic complications, while our case report shows that acute diabetes decompensation, such as DKA, can stimulate the occurrence and development of DMI. Timely diagnosis and appropriate treatment could shorten the recovery time.

Nr2e1 deficiency aggravates insulin resistance and chronic inflammation of visceral adipose tissues in a diet-induced obese mice model.

AIMS: To investigate the nuclear receptor subfamily 2 group E member 1 (Nr2e1) expression in adipose tissues of obese mice and assess the role of Nr2e1 in insulin resistance and chronic inflammation of the adipose tissues. MAIN METHODS: An obese model was established in Nr2e1 knockout (KO) mice and their wild type (WT) littermates through a long-term high-fat diet (HFD) feeding regime. The epididymal fat weight, body weight, and daily food intake were recorded. The blood lipid profile, blood inflammatory factors, and the levels of fasting blood glucose (FBG) and fasting insulin were determined. We estimated insulin resistance by the homeostasis model assessment (HOMA). The expression of inflammatory factors and F4/80 was examined by polymerase chain reaction (PCR) and western blotting to assess adipose tissues inflammation. We also determined the molecules of insulin signaling and the nuclear factor kappa B (NF-κB) pathway by western blotting. KEY FINDINGS: The Nr2e1 expression was upregulated in WT obese mice when compared with that in control mice. Despite a lower body weight and epididymal fat mass in Nr2e1-/- mice, these rats showed increased inflammatory cytokines secretion, more pronounced hyperlipidemia, and impaired insulin sensitivity after HFD treatment. Further investigation revealed that Nr2e1 deletion affected the expression of insulin signaling and NF-κB pathway-related molecules in visceral adipose tissues. SIGNIFICANCE: Nr2e1 may act as a potential target to improve insulin sensitivity and inflammation in obesity and related complications.

Sigma receptor knockdown augments dysfunction and apoptosis of beta cells induced by palmitate.

Sigma-1 receptor (Sig-1R) is located in the endoplasmic reticulum (ER) and clustered on the mitochondria related endoplasmic membranes, which are involved in the regulation of nervous system disease. Here, we designed Sig-1R silence MIN6 cells and studied the influence of Sig-1R silence on beta cells. We showed Sig-1R inactivation in MIN6 cells could not only decrease cell proliferation but also inhibit cell cycle, and this inhibitory effect on cell cycle might be achieved by regulating the FoxM1/Plk1/Cenpa pathway. Moreover, Sig-1R deficiency increased MIN6 cells sensitivity to lipotoxicity, exaggerated palmitate (PA)-induced apoptosis, and impaired insulin secretion. On the other hand, ER chaperone GRP78 and ER proapoptotic molecules CHOP increased in Sig-1R knockdown MIN6 cells. The ATP level decreased and reactive oxygen species (ROS) increased in this kind of cells. Furthermore not only GRP78 and CHOP levels, but also ATP and ROS levels changed more in Sig-1R silence cells after cultured with PA. Therefore, Sig-1R deficiency exaggerated PA induced beta cells apoptosis by aggravating ER stress and mitochondrial dysfunction. Together, our study showed that Sig-1R might influence the proliferation, apoptosis, and function of beta cells.

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study.

BACKGROUND: The relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association between SUA levels and the prevalence of non-alcoholic fatty liver disease (NAFLD), diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2,809 participants (1,784 males and 1,025 females) were included in this cross-sectional study. Clinical characteristics and the prevalence of each of the four diseases were analyzed based on gender-specific quartiles of SUA levels. The Pearson correlation analysis and linear-regression analysis were used to access the correlation between SUA levels and clinical characteristics. Furthermore, a binary logistic regression analysis was carried out to determine whether SUA was an independent risk factor for each of the four complications. RESULTS: SUA levels were positively correlated to BMI, BUN, Scr and TG, but negatively associated with eGFR, HDL, FBG, 2h-PG and HbA1c% for the patients with T2DM. The prevalence of NAFLD and DN, but not DR or DPN, were increased with SUA levels from the first to the fourth quartile. Binary logistic regression further disclosed that SUA was an independent risk factor for NAFLD (ORs Male = 1.002, ∗ P = 0.0013; ORs Female = 1.002, ∗ P = 0.015) and DN (ORs Male = 1.006, ∗ P < 0.001; ORs Female = 1.005, ∗ P < 0.001), but not for DR and DPN. After adjustment for the confounders, SUA levels were significantly associated with NAFLD within the 3rd (ORs = 1.829, P = 0.004) and 4th quartile (ORs = 2.064, P = 0.001) for women, but not independently associated with SUA for man. On the other hand, our results revealed increased prevalence of DN for SUA quartile 2 (ORs = 3.643, P = 0.039), quartile 3 (ORs = 3.967, P = 0.024) and quartile 4 (ORs = 9.133, P < 0.001) in men; however, SUA quartiles were significantly associated with DN only for quartile 4 (ORs = 4.083, P = 0.042) in women. CONCLUSION: For patients with T2DM, elevated SUA concentration is an independent risk factor for the prevalence of NAFLD and DN after adjustment for other indicators, but not DR or DPN.

Efficacy and safety of chiglitazar, a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial (CMAP).

Chiglitazar (Carfloglitazar) is a novel non-thiazolidinedione (TZD) structured peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies. This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone. Eligible patients were randomly assigned to receive chiglitazar 32 mg (n = 167), chiglitazar 48 mg (n = 166), or placebo (n = 202) once daily. The primary endpoint was the change in glycosylated hemoglobin A1c (HbA1c) at week 24 with superiority of chiglitazar over placebo. The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA1c, and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were -0.87% (95% confidential interval (CI): -1.10 to -0.65; P < 0.0001) and -1.05% (95% CI: -1.29 to -0.81; P < 0.0001), respectively. Secondary efficacy parameters including glycemic control, insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups. The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups. Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups. The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

A Retrospective Study of the C-Reactive Protein to Lymphocyte Ratio and Disease Severity in 108 Patients with Early COVID-19 Pneumonia from January to March 2020 in Wuhan, China.

BACKGROUND The aim of this study was to determine the effect of C-reactive protein (CRP), lymphocytes (LYM), and the ratio of CRP to LYM (CRP/LYM) on assessing the prognosis of COVID-19 severity at early stages of disease. MATERIAL AND METHODS A total of 108 hospitalized patients diagnosed with COVID-19 in Zhongnan Hospital of Wuhan University from January 17, 2020 to March 12, 2020 were enrolled. Data of demographic parameters, clinical characteristics, laboratory indicators, clinical manifestation, and outcome of disease were collected. The patients were divided into a severe group and a non-severe group according to diagnosis and classification, which followed the guidelines and management of the Chinese National Health Council COVID-19. The receiver-operating characteristic (ROC) analysis and comparison of ROC curves were used for the laboratory findings for assessment of COVID-19 severity. RESULTS Of the 108 patients, 42 patients (38.9%) were male and 24 patients (22.2%) were considered severe cases, with the mean age of 51.0 years old. Males and patients with comorbidities were more likely to become severe cases. CRP increased and LYM decreased in the severe group.The results for the areas under the curve (AUC) of CRP/LYM and CRP used to assess severe COVID-19 were 0.787 (95% CI 0.698-0.860, P<0.0001) and 0.781 (95% CI 0.693-0.856, P<0.0001), respectively; both results were better than that of LYM. The associated criterion value of CRP/LYM was calculated, with an excellent sensitivity of 95.83%. CONCLUSIONS The effect of CRP/LYM and CRP on the assessment for severe COVID-19 may be superior to LYM alone. CRP/LYM is a highly sensitive indicator to assess the severity of COVID-19 in the early stage of disease.

Obesity as a Potential Predictor of Disease Severity in Young COVID-19 Patients: A Retrospective Study.

OBJECTIVE: This study aims to explore the indicators for severity of coronavirus disease 2019 (COVID-19) in young patients between the ages of 18 and 40 years. METHODS: This retrospective cohort study included 65 consecutively admitted patients with COVID-19 who were between 18 and 40 years old in Zhongnan Hospital of Wuhan University in Wuhan, China. Among them, 53 were moderate cases, and 12 were severe or critical cases. Epidemiological, clinical, and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. RESULTS: The patients with severe/critical cases had obviously higher BMI (average 29.23 vs. 22.79 kg/m2 ) and lower liver computed tomography value (average 50.00 vs. 65.00 mU) than the group of moderate cases. The patients with severe/critical cases had higher fasting glucose, alanine aminotransferase, aspartate aminotransferase, and creatinine compared with patients with moderate cases (all P < 0.01). More severe/critical cases (58.33% vs. 1.92%) had positive urine protein levels. The severe/critical cases also experienced a significant process of serum albumin decline. Logistic regression analysis showed that male sex, high BMI (especially obesity), elevated fasting blood glucose, and urinary protein positivity were all risk factors for young patients with severe COVID-19. CONCLUSIONS: Obesity is an important predictor of COVID-19 severity in young patients. The main mechanism is related to damage of the liver and kidney.

Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis.

BACKGROUND: Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. METHODS: Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. RESULTS: The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3-89.9 %), 65.7 % (95CI 60.1-71.4 %), 42.4 % (95CI 32.2-52.6 %) and 21.4 % (95CI 15.3-27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1-9.3 %), hypertension was 15.6 % (95CI 12.6-18.6 %), cardiovascular disease was 4.7 % (95CI 3.1-6.2 %), and malignancy was 1.2 % (95CI 0.5-1.8 %). The complications, including ARDS risk, ranged from 5.6-13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7-10.8 %), AKI at 2.1 % (95CI 0.6-3.7 %), and shock at 4.7 % (95CI 0.9-8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0-61.9 %) and 41.7 % (95CI 26.4-56.9 %), respectively. CONCLUSION: Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.