Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.

PURPOSE: Numerous clinical studies have explored sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients. METHODS: A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www. CLINICALTRIALS: gov ) were also searched. RESULTS: A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: -253.36, - 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline. CONCLUSIONS: The SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.

Percutaneous kyphoplasty through unilateral puncture on the convex side for the treatment of painful osteoporotic vertebral compression fracture with scoliosis.

PURPOSE: To assess the clinical safety, accuracy, and efficacy of percutaneous kyphoplasty (PKP) surgery using an enhanced method of unilateral puncture on the convex side for the treatment of painful osteoporotic vertebral compression fractures (P-OVCF) with scoliosis. METHODS: Clinical and radiographic data of P-OVCF patients with scoliosis who underwent PKP via unilateral puncture on the convex side from January 2018 to December 2021 were retrospectively analyzed. This technique's detailed surgical steps and tips were described. The local kyphosis angle (LKA), scoliosis Cobb angle (SCA), and local scoliosis Cobb angle (LSCA) were measured using X-ray and compared at pre-operation, post-operation, and the last follow-up. The width of pedicle (POW), inner inclination angle (IIA), lateral distance (LD), and puncture course length (PCL) were measured on the axial computed tomography image and compared between two sides. Postoperative computed tomography was employed to evaluate the condition of cement distribution and puncture. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back pain (BP). RESULTS: Thirty-six patients, 23 women and 13 men, with an average age of 76.31 ± 6.28 years were monitored for 17.69 ± 4.70 months. The median surgical duration of single vertebrae was 35 min. The volume of bone cement for single vertebrae was 3.81 ± 0.87 ml and the proportion of sufficient cement distribution of the patients was 97.22. LKA was considerably improved from pre-operation to post-operation and sustained at the last follow-up. SCA and LSCA were not significantly modified between these three-time points. IIA, PCL, and LD were lower on the convex side than on the concave side. POW was considerably wider on the convex side. The ODI and VAS-BP scores were significantly improved after surgery and sustained during the follow-up. CONCLUSIONS: Combining with the proper assessment of the pre-injured life status of patients, PKP surgery using unilateral puncture on the convex side for the treatment of P-OVCF with scoliosis can achieve safe, excellent clinical, and radiographic outcomes.

Sodium benzoate induces pancreatic inflammation and ß cell apoptosis partially via benzoylation.

Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using ß-TC-6 cells, with 6 mM NAB or 100 µM benzoyl-CoA as stimuli, and 10 µM A485 (P300 inhibitor), 5 µM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 µM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet ß cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in ß cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of ß cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.

Tumor-induced osteomalacia characterized by "painful knee joint with difficulty in moving": a case report.

BACKGROUND: Tumor-related osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. The diagnosis of TIO can be very difficult because of its nonspecific nature of clinical manifestations. Here we reported a case of young TIO patient with "painful knee joint with difficulty in moving" to improve the clinical diagnosis and treatment levels. CASE PRESENTATION: The patient's clinical features were consistent with TIO. A tumor was successfully located in left tibial by 68Ga-DOTATATE PET/CT, and then was surgically resected. Upon pathologic assessment, the tumor was diagnosed as phosphaturia stromal tumor (PMT) with positive Vim staining. After the surgery, serum phosphate level rapidly recovered and symptoms significantly improved. CONCLUSION: TIO should be considered in patients with chronically hypophosphorus osteomalacia in the setting of no family history. Early removal of the responsible tumors is clinically essential for the treatment, and imaging examination is of great significance for tumor localization.

Association of lipid accumulation product with chronic kidney disease in Chinese community adults: a report from the REACTION study.

BACKGROUND: Limited studies regarding the correlation of lipid accumulation product (LAP) with a decreased estimated glomerular filtration rate (eGFR) have yielded conflicting findings, and no report has demonstrated the relationship of LAP with chronic kidney disease (CKD), defined as the presence of albuminuria and/or a decreased eGFR. The purpose of this study was to estimate the possible correlation of LAP with CKD prevalence in Chinese community adults. METHOD: In this cross-sectional study, LAP level of 7202 participants (age ≥ 40 years) was determined, and its possible association with CKD was evaluated by a multiple logistic regression model. RESULTS: Compared with subjects with non-CKD, non-albuminuria, and high eGFR, LAP levels significantly increased in female not male subjects with CKD, albuminuria, and low eGFR, respectively (all P < 0.001). The univariate logistic regression analysis revealed that LAP level of female not male subjects were significantly and positively associated with the prevalence of CKD (P < 0.001). The multivariate logistic regression analysis showed that the risk of CKD prevalence in female not male subjects progressively increased across LAP quartiles (P for trend < 0.01), and the risk of CKD prevalence of subjects in Q4 significantly increased compared to those in Q1 after adjustment for potential confounding factors in Models 4 (odds ratio [OR]: 1.382, 95% confidence intervals [CI] 1.002-1.906, P < 0.05). Stratified analysis revealed positive associations of LAP quartiles with risk of CKD prevalence in people with the following characteristics: women, older, overweight, with hypertension, normal glucose tolerance, appropriate low-density lipoprotein cholesterol, nonsmokers, nondrinkers, and no cardiovascular disease events. CONCLUSIONS: High LAP levels might be significantly associated with risk of CKD prevalence in community-dwelling Chinese female adults, which may inform both public health recommendations and clinical practice.

Association of circulating B-type natriuretic peptide with osteoporosis in a Chinese type 2 diabetic population.

BACKGROUND: Altered circulating levels and genetic variation of B-type natriuretic peptide (BNP), has been associated with lower bone mineral density (BMD) values and incidence of osteoporosis in peritoneal dialysis patients, renal transplant recipients, and postmenopausal women. The potential relationship of circulating BNP with osteoporosis in patients with type 2 diabetes mellitus (T2DM), however, has not yet been studied. METHODS: Circulating BNP levels were measured in 314 patients with T2DM, and participants were divided into normal BMD group (n = 73), osteopenia group (n = 120), and osteoporosis group (n = 121). The association of circulating BNP with diabetic osteoporosis and other parameters was analyzed. RESULTS: Circulating BNP was significantly higher in diabetic osteoporosis subjects than normal and osteopenia groups (P < 0.01 or P < 0.05). Circulating BNP levels correlated significantly and positively with neutrophil to lymphocyte ratio, systolic blood pressure, urinary albumin-to-creatinine ratio, and prevalence of hypertension, peripheral arterial disease, diabetic retinopathy, peripheral neuropathy, and nephropathy, and negatively with triglyceride, fasting blood glucose, lymphocyte count, hemoglobin, estimated glomerular filtration rate, bilirubin, osteoporosis self-assessment tool for Asians, BMD at different skeletal sites and corresponding T scores (P < 0.01 or P < 0.05). After multivariate adjustment, circulating BNP remained independently significantly associated with the presence of osteoporosis (odds ratio, 2.710; 95% confidence interval, 1.690-4.344; P < 0.01). BMD at the femoral neck and total hip and corresponding T scores were progressively decreased, whereas the prevalence of osteoporosis was progressively increased with increasing BNP quartiles (P for trend< 0.01). Moreover, receiver-operating characteristic analysis revealed that the optimal cutoff point of circulating BNP to indicate diabetic osteoporosis was 16.35 pg/ml. CONCLUSIONS: Circulating BNP level may be associated with the development of osteoporosis, and may be a potential biomarker for diabetic osteoporosis.

Association of Circulating Omentin-1 with Osteoporosis in a Chinese Type 2 Diabetic Population.

AIMS: Omentin-1, a newly identified adipokine, has been demonstrated to be associated with bone metabolism, but the results have been inconsistent. Moreover, the potential relationship of circulating omentin-1 with diabetic osteoporosis has never been reported. This study is intended for studying the association between circulating omentin-1, bone mineral density (BMD), prior fragility fractures, and other bone metabolic-related parameters. METHODS: Circulating omentin-1 levels were measured in 172 patients with type 2 diabetes mellitus (T2DM), and participants were divided into the normal BMD group (n = 52), the osteopenia group (n = 66), and the osteoporosis group (n = 54). The relationship between circulating omentin-1 and diabetic osteoporosis and other parameters was analyzed. RESULTS: Circulating omentin-1 was significantly higher in the osteoporosis group than in the normal group and in the osteopenia group (both P < 0.05). Circulating omentin-1 levels were correlated significantly and positively with sex; high-density lipoprotein cholesterol; apolipoprotein A; and prevalence of prior fragility fractures, diabetic nephropathy, and retinopathy; they were correlated negatively with diastolic blood pressure, triglyceride, hemoglobin, atherogenic index of plasma, osteoporosis self-assessment tool for Asians, BMD at different skeletal sites, and corresponding T scores, irrespective of age, sex, and body mass index (P < 0.01 or P < 0.05). Moreover, circulating omentin-1 was an independent decisive factor for the presence of osteoporosis only in women after multivariate adjustment (odds ratio: 1.069; 95% confidence interval: 1.003-1.139; P < 0.05). Lastly, the analysis of receiver operating characteristic curves revealed that the best cutoff value for circulating omentin-1 to predict diabetic osteoporosis was 15.37 ng/mL (sensitivity: 71.7%; specificity: 58.5%) in female subjects. CONCLUSIONS: High levels of circulating omentin-1 may be associated with the development of osteoporosis in female diabetic subjects and may be a potential biomarker for diabetic osteoporosis in women.

Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study.

Neuregulin-4 (Nrg4) is a novel adipokine associated with obesity, hyperglycemia, insulin resistance, dislipidemia, inflammation, and oxidative stress in mice and humans. However, no report has demonstrated the relationship of circulating Nrg4 with diabetic peripheral neuropathy (DPN). The objective of our study was to investigate the relationship between circulating Nrg4 and DPN in a cross-sectional study. Circulating Nrg4 levels were determined with an enzyme-linked immunosorbent assays kit in 132 newly diagnosed type 2 diabetes mellitus (nT2DM) patients and 41 normal controls (NC group). The associations of circulating Nrg4 with other parameters were also analyzed. Circulating Nrg4 levels were significantly lower in nT2DM patients with no DPN than in NC subjects, and were further markedly decreased in nT2DM patients with DPN (P < 0.01 or P < 0.05). Circulating Nrg4 levels were progressively decreased with an increasing number of abnormal DPN screening (P for trend < 0.01). Circulating Nrg4 levels correlated negatively with 8-iso-prostaglandin F2α (8-iso-PGF2α), high-sensitivity C-reactive protein (hs-CRP) and vibration perception threshold (VPT) (all P < 0.01), and 8-iso-PGF2α, hs-CRP, glycated hemoglobin A1c and VPT were independently related factors to circulating Nrg4 in nT2DM patients (P < 0.01 or P < 0.05). Moreover, circulating Nrg4 was significantly associated with the development of DPN even after controlling for anthropometric, biochemical and clinical parameters. Additionally, the analysis of receiver operating characteristic curves revealed that the best cutoff value for circulating Nrg4 to predict DPN was 1.58 ng/mL (sensitivity 90.91%, specificity 54.55%, and area under the curve 0.716). These findings together suggested that circulating Nrg4 levels were reduced in DPN patients and Nrg4 may be a novel adipokine associated with inflammation, oxidative stress, and long-term glycemic control in nT2DM patients.

Resistant starch ameliorated insulin resistant in patients of type 2 diabetes with obesity: a systematic review and meta-analysis.

BACKGROUND: Resistant starch (RS) is a starch that can be fermented by the microbial flora within gut lumen. Insulin resistance (IR) is a pathophysiological condition related to diabetes and obesity. RS could reduce blood glucose and ameliorate IR in animals, but its effect in human population is controversial. OBJECTIVE: The authors conducted a systematic literature review to evaluate the effect of RS diet supplement on ameliorating IR in patients with T2DM and simple obesity. METHODS: Databases that supplemented with RS in ameliorating IR in T2DM and simple obesity were queried for studies on or before August 15, 2018. Parameters including fasting insulin, fasting glucose, body mass index (BMI), homeostatic model assessment (HOMA) etc. were extracted from studies to systemically evaluate effects of RS. RESULTS: The database search yielded 14 parallel or crossover studies that met the inclusion criteria. The results indicated that there was no significant difference in the amelioration of BMI, HOMA-%S and HOMA-%B in T2DM patients between RS and the non-RS supplementation. However, the fasting blood glucose, fasting insulin and HOMA-IR in T2DM with obesity who supplemented RS were lower than control group, and the subgroup analysis according to the dose of RS supplementation was inconsistency. There was no significant difference between RS and non-RS supplements in patients with simple obesity. CONCLUSION: RS supplementation can ameliorate IR in T2DM, especially for the patients of T2DM with obesity, but not in simple obesity.

[Relationship between serum cystatin-C levels and vibrating perception threshold in patients with Type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between serum cystatin-C (Cys-c) levels and vibrating perception threshold (VPT) in patients with Type 2 diabetes mellitus (T2DM).
 METHODS: According to the symptoms, signs and results of lab examination, a total of 352 patients with T2DM were divided into a diabetic peripheral neuropathy group (DPN group, n=107) and a non-diabetic peripheral neuropathy group (NDPN group, n=245). Serum Cys-c levels were measured by radioimmunoassay method. The relationship between serum Cys-c levels and VPT, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), glucose and blood pressure and other parameters were also analyzed by correlation and multiple regression analysis. All T2DM patients were divided into a high Cys-c levels group (n=89) and a low Cys-c levels group (n=263) according to the upper quartile of Cys-c, and the incidence of DPN and VPT levels in each group were compared. Risk factors of DPN in T2DM patients were analyzed by binary logistic regression analysis and receiver operating characteristic (ROC) curve was used to identify the optimal cutoff of serum Cys-c levels for predicting DPN in patients with T2DM.
 RESULTS: Serum Cys-c levels were significantly higher in the DPN group than that in the NDPN group [(1.04±0.43) vs (0.80±0.25) mg/L, P<0.01]. Correlation analysis showed that serum Cys-c levels were positively correlated with age, body mass index (BMI), serum creatinine (SCr), blood urea nitrogen (BUN), ACR, VPT, pulse pressure (PP), white blood cell( WBC) , red cell distribution width (RDW), hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) (r=0.410, 0.115, 0.613, 0.433, 0.291, 0.300, 0.156, 0.129, 0.282, 0.314, 0.236, respectively, P<0.05 or P<0.01); and negatively correlated with diastolic blood pressure (DBP), eGFR and indirect bilirubin (IBIL) (r=-0.135, -0.647, -0.114, respectively, P<0.05 or P<0.01). Serum Cys-c levels in T2DM patients were positively correlated with VPT after adjusting for gender, age, BMI, ACR and eGFR (r=0.235, P<0.01). Multiple regression analysis revealed that VPT, age, SCr, eGFR, PP, ACR and HbA1C were independent related factors affecting serum Cys-c levels in T2DM patients. Compared with those in the low Cys-c levels group, the prevalence rate and VPT value was increased in the high Cys-c levels group (all P<0.01). Binary logistic regression analysis found that age, Cys-c and HbA1C were independent risk factors for predicting DPN in T2DM patients (all P<0.01). ROC curve analysis revealed that the optimal cutoff of Cys-c to predict DPN in T2DM patients was 0.996 mg/L, the sensitivity was 43.9%, the specificity was 83.7%, and the area under curve was 0.663.
 CONCLUSION: Serum Cys-c levels are well correlated with VPT in patients with T2DM. When the serum Cys-c levels>0.996 mg/L, the predicts have high risk of DPN in T2DM patients, which might be related to diabetic nephropathy, oxidative stress and inflammatory reaction induced by advanced age, hyperglycemia and hypertension.

The Association Between Triglyceride-Glucose Index and Its Combination with Obesity Indicators and Lower Extremity Peripheral Artery Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Lower extremity peripheral artery disease (LEAD) is a significant chronic complication of type 2 diabetes mellitus (T2DM) that significantly contributes to disability and mortality. The subtle presentation of LEAD symptoms often leads to underrecognition and misdiagnosis. Therefore, identifying simple and effective evaluation indicators is essential for the early detection and management of LEAD. Insulin resistance is closely associated with diabetes and its complications. However, the specific relationship between insulin resistance-measured by the triglyceride-glucose (TyG) index-and obesity indicators in relation to LEAD remains unclear. Objective: This study aims to investigate the association between the TyG index and its combination with obesity indicators in participants with T2DM and LEAD. Methods: We performed a univariate analysis on 3176 T2DM patients to identify risk factors for LEAD. Patients were then divided into quartiles based on the TyG index combined with various obesity indicators. The chi-square test was used to compare the prevalence of LEAD across these groups. Logistic regression analysis was conducted to examine the association between the TyG index, in combination with different obesity indicators, and the occurrence of LEAD. Finally, we assessed the predictive ability of the TyG index combined with obesity indicators for LEAD by comparing the area under the ROC curve (AUC). Results: The study included 3176 T2DM patients (1691 males and 1485 females) with a mean age of 56.16±10.60 years. Among them, 106 individuals had LEAD. The prevalence of LEAD varied significantly across quartiles of the TyG index, TyG-WC, and TyG-WHR (Q4 > Q3 > Q2 > Q1; P < 0.05). Multiple logistic regression analysis showed that the TyG index, TyG-WC, and TyG-WHR were positively associated with the risk of LEAD in T2DM patients. ROC curve analysis identified the best cutoff values for predicting LEAD: 9.8059 for the TyG index (sensitivity: 49.1%, specificity: 67.9%, AUC: 0.583), 808.8397 for TyG-WC (sensitivity: 70.8%, specificity: 47.8%, AUC: 0.603), and 8.8543 for TyG-WHR (sensitivity: 75.5%, specificity: 44.6%, AUC: 0.607). Conclusion: In T2DM patients, the TyG index, TyG-WHR, and TyG-WC are positively associated with the occurrence of LEAD. TyG-WHR and TyG-WC exhibit a stronger correlation with LEAD compared to the TyG index alone, indicating their superior diagnostic value.

Correlation between serum uric acid level and atrial fibrillation in patients with hyperthyroidism on medical data analysis context of IoT.

BACKGROUND: Dysfunctions in metabolism and endocrine systems are outcomes of disruptions in human physiological processes, often leading to disease onset. External factors can hinder the human body's innate capacity for self-regulation and healing, particularly when immune responses are compromised, allowing these factors to interfere with normal bodily functions directly. OBJECTIVE: To explore the effect of uric acid expression water in blood on the occurrence of atrial fibrillation in patients with hyperthyroidism, the expression level of uric acid in the blood and other physiological indexes were compared between patients with no symptoms of atrial fibrillation and patients with hyperthyroidism with symptoms of atrial fibrillation, to find the correlation between them. METHODS: A group of 112 hyperthyroidism patients who were admitted to our hospital from September 2019 to March 2020 were chosen and split into two groups. The control group consisted of 56 individuals (21 men and 35 women) aged between 16 and 86 years old, with an average age of 46.23 years (± 7.63). The observation group consisted of 56 individuals (24 males and 32 females) between 15 and 79 years, with an average age of 53.44 years (± 8.91). RESULTS: In the patients who were not treated with drugs before hospitalization the disease course and symptoms varied. The patients' clinical medical and demographic data were recorded and the patients' physiological indexes were obtained through blood tests and analysis. The differences between the two groups were analyzed by renal function, blood lipid index, thyroid function, and cardiac ultrasound, and these influencing factors were analyzed by regression analysis. The research adhered to ethical norms and ensured clear data presentation by using a rigorous technique to compare uric acid levels and physiological indicators among various patient groups. CONCLUSION: The study concentrated on the validation, repeatability, and contextual interpretation of data to provide a robust and rigorously scientific comparison. The most common is the increase of uric acid in the blood, which can induce other diseases, and atrial fibrillation is one of the most common diseases of cardiovascular diseases.

Association of Circulating Carbohydrate Antigen 19-9 Level with Type 2 Diabetic Kidney Disease in Chinese Adults: A Cross-Sectional Study.

Objective: Very few and conflicting data are available regarding the correlation between circulating carbohydrate antigen 19-9 (CA19-9) levels and diabetic kidney disease (DKD) and its components including albuminuria and a low estimated glomerular filtration rate (eGFR). This study aimed to examine the association of circulating CA19-9 and DKD in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 402 hospitalized T2DM patients between September 2017 and December 2021 were included in this cross-sectional study. There were 224 and 178 subjects in non-DKD and DKD groups, respectively. Serum CA19-9 was measured by chemiluminescence method, and its potential relationship with DKD was evaluated by multivariate logistic regression and correlation analyses, and receiver operating characteristic (ROC) curve analysis. Results: T2DM patients with DKD had significantly higher serum CA19-9 levels than those without, and serum CA19-9 levels were positively related to urinary albumin-to-creatinine ratio and negatively to eGFR (P<0.01). Multivariate regression analysis revealed that serum CA 19-9 was an independent factor of DKD [odds ratio (OR), 1.018; 95% confidence interval (CI), 1.002-1.035; P<0.05]. Moreover, an increased progressively risk of DKD with an increase in serum CA19-9 quartiles was observed (P for trend <0.001), and T2DM patients in the highest serum CA19-9 quartile were associated with an increased likelihood of DKD when compared to those in the lowest quartile (OR: 2.936, 95% CI 1.129-7.633, P<0.05). Last, the analysis of ROC curves suggested that serum CA 19-9 at a cut of 25.09 U/mL resulted in the highest Youden index with sensitivity 43.8% and 75.4% specificity to predict the presence of DKD. Conclusion: These results showed that high circulating CA19-9 was related to DKD and may serve as a useful biomarker of DKD in hospitalized Chinese T2DM patients.

Positive Association of Pulse Pressure with Presence of Albuminuria in Chinese Adults with Prediabetes: A Community-Based Study.

Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.

Identifying diagnostic indicators for type 2 diabetes mellitus from physical examination using interpretable machine learning approach.

Background: Identification of patients at risk for type 2 diabetes mellitus (T2DM) can not only prevent complications and reduce suffering but also ease the health care burden. While routine physical examination can provide useful information for diagnosis, manual exploration of routine physical examination records is not feasible due to the high prevalence of T2DM. Objectives: We aim to build interpretable machine learning models for T2DM diagnosis and uncover important diagnostic indicators from physical examination, including age- and sex-related indicators. Methods: In this study, we present three weighted diversity density (WDD)-based algorithms for T2DM screening that use physical examination indicators, the algorithms are highly transparent and interpretable, two of which are missing value tolerant algorithms. Patients: Regarding the dataset, we collected 43 physical examination indicator data from 11,071 cases of T2DM patients and 126,622 healthy controls at the Affiliated Hospital of Southwest Medical University. After data processing, we used a data matrix containing 16004 EHRs and 43 clinical indicators for modelling. Results: The indicators were ranked according to their model weights, and the top 25% of indicators were found to be directly or indirectly related to T2DM. We further investigated the clinical characteristics of different age and sex groups, and found that the algorithms can detect relevant indicators specific to these groups. The algorithms performed well in T2DM screening, with the highest area under the receiver operating characteristic curve (AUC) reaching 0.9185. Conclusion: This work utilized the interpretable WDD-based algorithms to construct T2DM diagnostic models based on physical examination indicators. By modeling data grouped by age and sex, we identified several predictive markers related to age and sex, uncovering characteristic differences among various groups of T2DM patients.

Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.

Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.

Sodium Crotonate Alleviates Diabetic Kidney Disease Partially Via the Histone Crotonylation Pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, inflammation and fibrosis play an important role in its progression. Histone lysine crotonylation (Kcr) was first identified as a new type of post-translational modification in 2011. In recent years, prominent progress has been made in the study of sodium crotonate (NaCr) and histone Kcr in kidney diseases. However, the effects of NaCr and NaCr-induced Kcr on DKD remain unclear. In this study, db/db mice and high glucose-induced human tubular epithelial cells (HK-2) were used respectively, and exogenous NaCr and crotonoyl-coenzyme A (Cr-CoA) as intervention reagents, histone Kcr and DKD-related indicators were detected. The results confirmed that NaCr had an antidiabetic effect and decreased blood glucose and serum lipid levels and alleviated renal function and DKD-related inflammatory and fibrotic damage. NaCr also induced histone Kcr and histone H3K18 crotonylation (H3K18cr). However, NaCr and Cr-CoA-induced histone Kcr and protective effects were reversed by inhibiting the activity of Acyl-CoA synthetase short-chain family member 2 (ACSS2) or histone acyltransferase P300 in vitro. In summary, our data reveal that NaCr may mitigate DKD via an antidiabetic effect as well as through ACSS2 and P300-induced histone Kcr, suggesting that Kcr may be the potential molecular mechanism and prevention target of DKD.

Development of Serum Lactate Level-Based Nomograms for Predicting Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Purpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P<0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17-99% and 0.36, and 24-99% and 0.24 for the models in normal lactate and high lactate groups, respectively. Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.

Bioinspired yeast-based ß-glucan system for oral drug delivery.

Oral drug delivery is the preferred route of drug administration for patients, especially those who need long-term medication. Recently, bioinspired drug delivery systems have emerged for the oral delivery of various therapeutics. Among them, the yeast-based ß-glucan system is a novel and promising platform, for oral administration that can overcome the biological barriers of the harsh gastrointestinal environment. Remarkably, the yeast-based ß-glucan system not only protects the drug through the harsh gastrointestinal environment but also achieves targeted therapeutic effects by specifically recognizing immune cells, especially macrophages. Otherwise, it exhibits immunomodulatory properties. Based on the pleasant characteristics of the yeast-based ß-glucan system, they are widely used in various macrophage-related diseases for oral administration. In this review, we introduced the structure and function of yeast-based ß-glucan. Subsequently, we further summarized the current preparation methods of yeast-based ß-glucan carriers and the strategies for preparing yeast-based ß-glucan drug delivery systems. In addition, we focus on discussing the applications of ß-glucan drug delivery systems in various diseases. Finally, the current challenges and future perspectives of the ß-glucan drug delivery system are introduced.

Aspartate aminotransferase/alanine aminotransferase ratio was associated with type 2 diabetic peripheral neuropathy in a Chinese population: A cross-sectional study.

Objective: Despite previous research that focused on aspartate aminotransferase/alanine aminotransferase ratio (AAR) as predictors of type 2 diabetes mellitus (T2DM) and cardiovascular disease, there has been limited research evaluating the association between AAR and diabetic microvascular complications. This study aimed to investigate the association of AAR with diabetic peripheral neuropathy (DPN). Methods: A total of 1562 hospitalized patients with T2DM were divided into four groups according to AAR quartiles. The relationship between AAR and DPN and related parameters was explored by the Spearman correlation coefficients, multivariable logistic regression analysis, and receiver operating characteristic (ROC) curves. Results: Patients with higher AAR quartiles had higher levels of vibration perception threshold (VPT) and presence of DPN, and AAR was positively associated with VPT and presence of DPN independent of sex, age, body mass index, and diabetic duration (P<0.01 or P<0.05). Moreover, AAR remained significantly associated with a higher odds ratio (OR) of DPN (OR 2.413, 95% confidence interval [CI] 1.081-5.386, P<0.05) after multivariate adjustment. Additionally, the risk of presence of DPN increased progressively as AAR quartiles increased (all P for trend <0.01) in both male and female subjects, and the highest quartile of AAR of male and female subjects was respectively associated with 107.3% (95% CI: 1.386-3.101; P<0.01) and 136.8% (95% CI: 1.550-3.618; P<0.01) increased odds of DPN compared with the lower quartiles. Last, the analysis of receiver operating characteristic curves revealed that the best cutoff values for AAR to predict the presence of DPN were 0.906 (sensitivity: 70.3%; specificity: 49.2%; and area under the curve [AUC]: 0.618) and 1.402 (sensitivity: 38%; specificity: 81.9%; and AUC: 0.600) in male and female subjects, respectively. Conclusions: These findings suggest that the high AAR may be associated with the presence of DPN in Chinese patients with T2DM, and may be used as an additional indicator of risk of DPN.