Analysis of the association between high antioxidant diet and lifestyle habits and diabetic retinopathy based on NHANES cross-sectional study.

Oxidative stress plays a crucial role in increasing the risk of developing diabetic retinopathy (DR). The oxidative balance score (OBS) and the composite dietary antioxidant index (CDAI) are two tools for assessing the effects of diet and lifestyle on oxidative stress. The aim of this study was to investigate the association between OBS, CDAI and the occurrence of DR. After controlling for potential confounders, OBS was negatively associated with DR with an odds ratio (OR) of 0.976 and a 95% confidence interval (CI) of 0.956-0.996, suggesting that for every unit increase in OBS, the risk of DR was reduced by 2.4%. In contrast, the relationship between OBS and CDAI was not significant (P > 0.05), suggesting that it was OBS, not CDAI, that contributed to the reduced risk of diabetic retinopathy. After adjusting for potential confounders, OBS was negatively associated with DR (OR: 0.976; 95% CI 0.956-0.996), but this association was not found in CDAI (P > 0.05), suggesting that for every one-unit increase in OBS, there was a 2.4% reduction in the risk of developing DR. This study suggests that a diet and lifestyle high in OBS reduces the risk of developing DR, which provides a rationale for nutritional interventions to prevent DR.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Association of congenital iodine deficiency syndrome and differentiated thyroid cancer: a Mendelian randomization study.

BACKGROUND: The effect of iodine deficiency, especially during the fetal period, on thyroid cancer risk remains unclear. The evidence from observational studies is controversial because of the inevitable confounding factors. We studied the causal effect of congenital iodine deficiency on differentiated thyroid cancer (DTC) based on Mendelian randomization (MR). METHODS: Two-Sample MR analysis was performed using data from published genome-wide association studies, including congenital iodine deficiency syndrome (CIDS) (353 cases, 187,684 controls) and DTC (649 cases, 431 controls) data. RESULTS: There was a causal relationship between CIDS and DTC (P < 0.05), with CIDS increasing the DTC risk by 37.4% (OR = 1.374, 95%CI = 1.110-1.700). Heterogeneity tests and tests of multiple validities indicated that the results were solid and reliable (all P < 0.05). CONCLUSIONS: Fetal iodine deficiency increases the risk of DTC, so future clinical studies should focus on the effect of iodine supplementation during pregnancy to reduce the risk of thyroid cancer in the offspring.

Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

BRAFV600E genetic testing should be recommended for Bethesda III or V thyroid nodules based on fine-needle aspiration.

The preoperative diagnosis of thyroid nodules now routinely includes BRAFV600E genetic testing in most provincial and municipal hospitals in China. This study identified the most suitable patients of thyroid nodule for BRAFV600E genetic testing. We retrospectively collected data of patients from the Hospital Information System that had undergone fine needle aspiration biopsy (FNAB) from May 2019 to December 2021. Data of FNAB, BRAFV600E genetic testing, and post-surgical pathological diagnosis were collected. A total of 12,392 patients were included in this study. Among them, 7,010 patients underwent solely FNAB, while 5,382 patients had both FNAB and BRAFV600E genetic testing. In the FNAB group, 2,065 thyroid nodules were surgically removed, with a 93.12% malignancy rate. In the FNAB + BRAF group, 2,005 nodules were dissected, and the malignancy rate was 98.20%. However, it was evident that in the subgroups, the combination of FNAB and BRAFV600E genetic testing only benefited Bethesda III (p < 0.001) and V (p = 0.001) nodules. Overall, the combination of FNAB with BRAFV600E genetic testing significantly improved the malignancy rate of surgical thyroid nodes at our hospital when compared to FNAB alone. The subgroup analysis showed that BRAFV600E genetic testing only benefited Bethesda III and V nodules. These findings provide a clinical reference for rationally selecting the most suitable population for BRAFV600E genetic testing.

Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic ß cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy.

BACKGROUND: Diabetes and obesity are associated with muscle atrophy that reduces life quality and lacks effective treatment. Mesenchymal stromal cell (MSC)-based therapy can ameliorate high fat-diet (HFD) and immobilization (IM)-induced muscle atrophy in mice. However, the effect of MSCs on muscle atrophy in type 2 diabetes mellitus (T2DM) and the potential mechanism is unclear. Here, we evaluated the efficacy and explored molecular mechanisms of human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes (MSC-EXO) on diabetes- and obesity-induced muscle atrophy. METHODS: Diabetic db/db mice, mice fed with high-fat diet (HFD), mice with hindlimb immobilization (IM), and C2C12 myotubes were used to explore the effect of hucMSCs or MSC-EXO in alleviating muscle atrophy. Grip strength test and treadmill running were used to measure skeletal muscle strength and performance. Body composition, muscle weight, and muscle fibre cross-sectional area (CSA) was used to evaluate muscle mass. RNA-seq analysis of tibialis anterior (TA) muscle and Western blot analysis of muscle atrophy signalling, including MuRF1 and Atrogin 1, were performed to investigate the underlying mechanisms. RESULTS: hucMSCs increased grip strength (P = 0.0256 in db/db mice, P = 0.012 in HFD mice, P = 0.0097 in IM mice), running endurance (P = 0.0154 in HFD mice, P = 0.0006 in IM mice), and muscle mass (P = 0.0004 in db/db mice, P = 0.0076 in HFD mice, P = 0.0144 in IM mice) in all models tested, with elevated CSA of muscle fibres (P < 0.0001 in db/db mice and HFD mice, P = 0.0088 in IM mice) and reduced Atrogin1 (P = 0.0459 in db/db mice, P = 0.0088 in HFD mice, P = 0.0016 in IM mice) and MuRF1 expression (P = 0.0004 in db/db mice, P = 0.0077 in HFD mice, P = 0.0451 in IM mice). MSC-EXO replicated all these hucMSC-mediated changes (P = 0.0103 for grip strength, P = 0.013 for muscle mass, P < 0.0001 for CSA of muscle fibres, P = 0.0171 for Atrogin1 expression, and P = 0.006 for MuRF1 expression). RNA-seq revealed that hucMSCs activated the AMPK/ULK1 signalling and enhanced autophagy. Knockdown of AMPK or inhibition of autophagy with 3-methyladenine (3-MA) diminished the beneficial anti-atrophy effects of hucMSCs or MSC-EXO. CONCLUSIONS: Our results suggest that human umbilical cord mesenchymal stromal cells mitigate diabetes- and obesity-induced muscle atrophy via enhancing AMPK/ULK1-mediated autophagy through exosomes, with implications of applying hucMSCs or hucMSC-derived exosomes to treat muscle atrophy.

BRAF p.V600E genetic testing based on ultrasound-guided fine-needle biopsy improves the malignancy rate in thyroid surgery: our single-center experience in the past 10 years.

PURPOSE: Ultrasound-guided fine-needle aspiration biopsy (UG-FNAB) was implemented in Qilu Hospital of Shandong University in 2015 as a preoperative diagnostic method for thyroid surgery. BRAF p.V600E genetic testing was implemented in 2019. This study evaluated the impact of these two tests on the malignancy rate in patients undergoing thyroidectomy. METHODS: A total of 19,496 patients were included in the study. We retrospectively collected data from patients undergoing thyroid surgery in the Hospital Information System (HIS) of Qilu Hospital of Shandong University from January 2012 to December 2021. Meanwhile, data of FNAB, UG-FNAB, and BRAF p.V600E genetic testing were collected. Differences in means among groups were analyzed via one-way ANOVA, and differences in frequencies were analyzed via Pearson's chi-squared test. RESULTS: In this study, the 10-year period was divided into three stages, with the implementation of UG-FNAB in 2015 and that of BRAF p.V600E genetic testing in 2019 as dividing lines. The malignancy rate in thyroid surgery increased significantly during these three stages (48.06% vs. 73.47% vs. 88.17%; P < 0.001). In the same period (May 2019 to December 2021), the malignancy rate in thyroid surgery was significantly different between the Non-FNAB, UG-FNAB, and UG-FNAB-BRAF groups (78.87% vs. 95.63% vs. 98.32%; P < 0.001). CONCLUSIONS: The successful implementation of UG-FNAB and BRAF p.V600E genetic testing improved the malignancy rate in thyroid surgery and reduced unnecessary diagnostic surgery for benign and marginal lesions. It can, therefore, provide a clinical reference for other hospitals.

Engineered Sandwich-Structured Composite Wound Dressings with Unidirectional Drainage and Anti-Adhesion Supporting Accelerated Wound Healing.

Proper management of exudate is of great clinical value for reducing wound infection and promoting wound healing, thus various dressings have been studied to address this widespread medical challenge. Herein, a novel sandwich-structured composite wound dressing (SCWD), integrating of a superlyophobic (SLO) polydimethylsiloxane (PDMS) layer, a superlyophilic gauze layer, and a lyophobic PDMS layer is presented, with particular unidirectional droplet drainage and stable anti-adhesion capabilities, which realizes effective management of wound exudate and provides a favorable environment for wound healing. Thanks to the stable SLO property on the PDMS surface with hierarchical micro/nanostructures, the continuously accumulated wound exudate at the interface between dressing and wound surface is gradually deformed, eventually passing through SLO PDMS layer through milli-scale channels and being absorbed by gauze layer. Experimental results show that the application of SCWD can significantly reduce the occurrence of wound infection, avoid the tearing of wound tissues when replacing dressings, and accelerate wound healing by ≈20%. The combination of SCWD and lyophilized powders of stem cells supernatant (LPSCS) is verified to better accelerate the healing process. The proposed method offers great potential in clinical applications, particularly for acute trauma wound treatments.

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial-to-mesenchymal transition via miR-424-5p.

Diabetic kidney disease (DKD) is well-acknowledged as one of the most common complications in diabetes mellitus. Recent studies have demonstrated the promising role of mesenchymal stem cell-derived exosomes (MSC-exos) as a cell-free treatment strategy for DKD. The present study sought to investigate the therapeutic potential and the underlying mechanisms of MSC-exos in DKD. The authentication of MSC-exos was validated by western blot, transmission electron microscope (TEM), and nanosight tracking analysis (NTA). Apoptosis was detected by western blot, TUNEL staining, and flow cytometry. Epithelial-to-mesenchymal transition (EMT) was evaluated by western blot and immunofluorescence. The relationship between miR-424-5p and Yes-associated protein 1 (YAP1) was revealed by dual luciferase reporter assay. We observed that MSC-exos could attenuate DKD by decreasing cell apoptosis and inhibiting epithelial-to-mesenchymal transition (EMT) in diabetic kidneys in db/db mice. Besides, we documented that MSC-exos could reverse high glucose-induced apoptosis and EMT in HK2 cells. Interestingly, miR-424-5p derived from MSC-exos could inhibit YAP1 activation in HK2 cells, resulting in alleviation of high glucose-induced cell apoptosis and EMT. Our study provides novel insights into MSC-exos-mediated protective effect in DKD. MSC-exos could inhibit high glucose-induced apoptosis and EMT through miR-424-5p targeting of YAP1.

Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (RUNX2) gene. OBJECTIVE: Identification and functional characterization of RUNX2 mutation associated with CCD. METHODS: We performed genetic testing of a patient with CCD using whole exome sequencing and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay. RESULTS: We found a novel RUNX2 frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant RUNX2 and wild-type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter. CONCLUSIONS: We explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in RUNX2 transactivation ability.

Mesenchymal stem cell-derived exosomal miR-146a reverses diabetic ß-cell dedifferentiation.

BACKGROUND: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional ß-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown. METHODS: Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on ß-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a. RESULTS: Our results showed that bmMDEs reversed diabetic ß-cell dedifferentiation and improved ß-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved ß-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of ß-catenin signaling in ß-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve ß-cell function. CONCLUSIONS: These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic ß-cell dysfunction by acting on the NUMB/ß-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM.

Mesenchymal stem cell-conditioned medium alleviates high fat-induced hyperglucagonemia via miR-181a-5p and its target PTEN/AKT signaling.

BACKGROUND: α-cell dysregulation gives rise to fasting and postprandial hyperglycemia in type 2 diabetes mellitus(T2DM). Administration of Mesenchymal stem cells (MSCs) or their conditioned medium can improve islet function and enhance insulin secretion. However, studies showing the direct effect of MSCs on islet α-cell dysfunction are limited. METHODS: In this study, we used high-fat diet (HFD)-induced mice and α-cell line exposure to palmitate (PA) to determine the effects of bone marrow-derived MSC-conditioned medium (bmMSC-CM) on glucagon secretion. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay(ELISA). To investigate the potential signaling pathways, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT and phosphorylated AKT(p-AKT) were assessed by Western blotting. RESULTS: In vivo, bmMSC-CM infusion improved the glucose and insulin tolerance and protected against HFD-induced hyperglycemia and hyperglucagonemia. Meanwhile, bmMSC-CM infusion ameliorated HFD-induced islet hypertrophy and decreased α- and ß-cell area. Consistently, in vitro, glucagon secretion from α-cells or primary islets was inhibited by bmMSC-CM, accompanied by reduction of intracellular PTEN expression and restoration of AKT signaling. Previous studies and the TargetScan database indicate that miR-181a and its target PTEN play vital roles in ameliorating α-cell dysfunction. We observed that miR-181a-5p was highly expressed in BM-MSCs but prominently lower in αTC1-6 cells. Overexpression or downregulation of miR-181a-5p respectively alleviated or aggravated glucagon secretion in αTC1-6 cells via the PTEN/AKT signaling pathway. CONCLUSIONS: Our observations suggest that MSC-derived miR-181a-5p mitigates glucagon secretion of α-cells by regulating PTEN/AKT signaling, which provides novel evidence demonstrating the potential for MSCs in treating T2DM.

High concentrations of triglycerides are associated with diabetic kidney disease in new-onset type 2 diabetes in China: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

AIMS: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. METHODS: In total, 11 142 patients with new-onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011-2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow-up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow-up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high-density lipoprotein cholesterol (HDL-c) was defined by HDL-c <1.0 mmol/L for men or <1.3 mmol/L for women. RESULTS: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL-c at both baseline and follow-up visits. The DKD group also had higher levels of post-load plasma glucose and TG at follow-up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p = .012) and high TG at follow-up (OR = 1.71, p < .001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow-up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p < .001) after adjustment for covariates. CONCLUSIONS: In a large population of patients with new-onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD.

Nomogram Predicting the Risk of Progression from Prediabetes to Diabetes After a 3-Year Follow-Up in Chinese Adults.

PURPOSE: To develop a nomogram for predicting the risk of progression from prediabetes to diabetes and provide a quantitative predictive tool for early clinical screening of high-risk populations of diabetes. MATERIALS AND METHODS: This study was a retrospective cohort study and part of the investigation conducted for the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 1857 prediabetic participants at baseline underwent oral glucose tolerance test and hemoglobin A1c (HbA1c) testing after 3 years. The areas under the receiver operating characteristic curves (AUCs) were adopted to measure the predictive value of progression to diabetes, using baseline fasting plasma glucose (FPG), 2-hr postprandial plasma glucose (2hPG), HbA1c or combined models. Decision curve analysis determined the model with the best discriminative ability. A nomogram was formulated and internally validated, providing an individualized predictive tool by calculating total scores. RESULTS: After 3 years, 145 participants developed diabetes, and the annual incidence was estimated to be 2.60%. Among the three single indicators and four combined models, model 4 combined of FPG, 2hPG, and HbA1c showed the best performance in risk predication, with an AUC of 0.742. The nomogram constructed via model 4 was validated and demonstrated good prediction for the risk of diabetes. The nomogram score/predicted probability was a numeric value representing the prediction model score of individual patients. Notably, all nomogram scores showed relatively high negative predictive values. CONCLUSION: The nomogram constructed in this study effectively predicts and quantifies the risk of progression from prediabetes to diabetes after a 3-year follow-up and could be adopted to identify Chinese patients at high risk for diabetes in order to provide timely interventions.

Self-reported snoring is associated with chronic kidney disease in obese but not in normal-weight Chinese adults.

BACKGROUND: The relationship between sleeping disorders and chronic kidney disease (CKD) has already been reported. Snoring, a common clinical manifestation of obstructive sleep apnea-hypopnea syndrome, is of clinical value in assessing sleeping disorder severity. However, investigations of the connection between snoring and CKD are limited, especially in normal-weight populations. This study assessed the relationship between snoring frequency and CKD in obese and normal-weight people in China. METHODS: A community-based retrospective cross-sectional study of 3250 participants was performed. Study participants were divided into three groups - the regularly snoring group, occasionally snoring group, and never snoring group - based on their self-reported snoring frequency. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2. Multiple logistic regression analysis was used to explore the relevance between snoring frequency and CKD prevalence. RESULTS: The CKD prevalence in obese participants was higher than that in normal-weight participants. Frequent snorers had a higher prevalence of CKD than those who were not frequent snorers in the obese group. Snoring frequency was correlated with CKD prevalence in obese participants independent of age, sex, smoking and drinking status, systolic blood pressure, triglyceride level, high-density lipoprotein, and homeostasis model assessment of insulin resistance (odds ratio: 2.66; 95% CI: 1.36-5.19; p=.004), while the same relationships did not exist in normal-weight participants (odds ratio: 0.79; 95% CI: 0.32-1.98; p=.614). CONCLUSIONS: Snoring appears to be independently associated with CKD in obese but not in normal-weight Chinese adults.

Malnutrition Contributes to Low Lymphocyte Count in Early-Stage Coronavirus Disease-2019.

Background and Aim: Lymphocytes play an important role in fighting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Low total lymphocyte count (TLC), which contributes to poor clinical outcomes, is common in persons with coronavirus disease 2019 (COVID-19). The current explanation for the cause of low TLC is that it is directly related to the invasiveness of SARS-CoV-2, which attacks lymphocytes. We hypothesized that malnutrition contributes to the development of low TLC in early-stage COVID-19. Methods: We prospectively enrolled 101 patients with confirmed COVID-19. On their first day of hospitalization, we collected baseline and laboratory data, including clinical symptoms; the Sequential Organ Failure Assessment, Nutrition Risk Screening 2002 and Subjective Global Assessment were used to assess the malnutrition status of the patients. Multivariable logistic regression was used to identify independent risk factors for low TLC and severe COVID-19. Results: Malnutrition was associated with lower TLC in COVID-19. Fifty-nine (58.4%) of the patients showed low TLC, 41 (40.6%) were at risk for malnutrition, and 18 of them were malnourished. Low TLC was an independent risk factor for severe COVID-19. Compared to patients with normal TLC, those with low TLC more often presented with anorexia, malnutrition, higher SOFA scores (P < 0.05) and comorbidities (diabetes and malignancies). Malnutrition (OR: 3.05, 95% CI: 1.5-6.19, P = 0.006) and SOFA scores (OR: 1.51, 95% CI: 1.04-2.43, P = 0.042) were identified as independent risk factors for low TLC. Conclusions: Malnutrition was common among our patients with early-stage COVID-19, and it contributed to the occurrence of low TLC.

Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy.

BACKGROUND: Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). METHODS: HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. RESULTS: HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. CONCLUSIONS: These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients.

Enterotype Bacteroides Is Associated with a High Risk in Patients with Diabetes: A Pilot Study.

BACKGROUND: More and more studies focus on the relationship between the gastrointestinal microbiome and type 2 diabetes, but few of them have actually explored the relationship between enterotypes and type 2 diabetes. Materials and Methods. We enrolled 134 patients with type 2 diabetes and 37 nondiabetic controls. The anthropometric and clinical indices of each subject were measured. Fecal samples of each subject were also collected and were processed for 16S rDNA sequencing. Multiple logistic regression analysis was used to determine the associations of enterotypes with type 2 diabetes. Multiple linear regression analysis was used to explore the relationship between lipopolysaccharide levels and insulin sensitivity after adjusting for age, BMI, TG, HDL-C, DAO, and TNF-α. The correlation analysis between factors and microbiota was identified using Spearman correlation analysis. The correlation analysis between factors was identified using partial correlation analysis. RESULTS: Gut microbiota in type 2 diabetes group exhibited lower bacterial diversity compared with nondiabetic controls. The fecal communities from all subjects clustered into two enterotypes distinguished by the levels of Bacteroides and Prevotella. Logistic regression analysis showed that the Bacteroides and Bacteroides and Prevotella enterotype. Partial correlation analysis showed that lipopolysaccharide was closely associated with diamine oxidase, tumor necrosis factor-alpha, and Gutt insulin sensitivity index after adjusting for multiple covariates. Furthermore, the level of lipopolysaccharide was found to be an independent risk factor for insulin sensitivity. CONCLUSIONS: We identified two enterotypes, Bacteroides and Prevotella, among all subjects. Our results showed that the Bacteroides enterotype was an independent risk factor for type 2 diabetes, which was due to increased levels of lipopolysaccharide causing decreased insulin sensitivity.Bacteroides and Prevotella enterotype. Partial correlation analysis showed that lipopolysaccharide was closely associated with diamine oxidase, tumor necrosis factor-alpha, and Gutt insulin sensitivity index after adjusting for multiple covariates. Furthermore, the level of lipopolysaccharide was found to be an independent risk factor for insulin sensitivity. Bacteroides and.