Tumor necrosis factor-α-stimulated gene-6(TSG-6), a secreted protein with anti-inflammatory and tissue-protective properties, mediates a cascade of proinflammatory cytokines and ameliorates tissue fibrosis. Previous studies have found that TSG-6 can attenuate the degree of fibrosis, inhibit the inflammatory response, and reduce adipogenesis in orbital tissues in a Thyroid Eye Disease (TED) mouse model of thyroid-eye disease; however, the exact mechanism has not been elucidated. In the present study, we investigated the mechanism by which TSG-6 exerts its anti-inflammatory and antifibrotic effects in an in vitro cellular model of TED. Human orbital connective tissue was collected from primary and passaged cultures and 3-5 passages-cells were used in subsequent experiments. The expression of relevant inflammatory markers, including tumor necrosis factor-α(TNF-α), Interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), Cyclooxygenase-2(COX-2), and intercellular cell adhesion molecule-1(ICAM-1), was detected by western blotting with 5, 10, and 15 ng/ml TSG-6 pretreatment in the presence or absence of 10 ng/ml Interleukin-1beta (IL-1β) and H2DCFDA (DCFH-DA) fluorescent staining, and flow cytometry was used to detect reactive oxygen species(ROS) indices. Orbital fibroblasts (OF) were treated with TSG-6 in the presence or absence of transforming growth factor-beta 1(TGF-β1) agonist (SRI-011381:MCE, HY-100347) and the expression of TGF-β1/Smad pathway-associated fibrosis factors, including α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and collagen type 1 (COL1A1). TSG-6 inhibited IL-1β-induced production of the inflammatory mediators TNF-α, IL-6, MCP-1, COX-2, and ICAM-1, and the release of ROS in a dose-dependent manner in an in vitro cell model of TED. TSG-6 downregulated the expression of TGF-β1, Smad2/3, p-smad2/3, α-SMA, CTGF, and COL1A1 in a dose-dependent manner after TGF-β1 pretreatment and reduced the phosphorylation of Smad2/3, suggesting that TSG-6 inhibits the TGF-β1 signaling cascade response in orbital fibroblasts. TSG-6 inhibited the production of inflammatory mediators and the release of ROS, and suppressed fibrosis of human orbital fibroblasts by downregulating the TGF-β1/Smad pathway. These data suggest a potential application of TSG-6 in the treatment of TED and provide a novel target for the treatment of TED.

Purpose:Ketosis-prone diabetes (KPD) is a new subtype of diabetes distinct from traditional type 2 diabetes, and the role of muscle mass in KPD remains unclear. Serum creatinine-to-cystatin C ratio (CCR) has been identified as a marker of muscle mass. The present study aims to investigate the value of CCR in newly diagnosed KPD. Methods:Two hundred and ninety patients with newly diagnosed T2D were included in the study and were divided into T2D (n = 195) and KPD (n = 95) groups according to the occurrence of ketosis. The cutoff value of CCR in identifying KPD was analyzed by receiver operating characteristic (ROC) curves. Logistic regression was used to assess the relationship between CCR and KPD and the independent influences on KPD. Results:The serum CCR level of the KPD group was significantly higher than that of the T2D group. After adjustment for all confounders, the risk of KPD was significantly increased with elevated CCR levels. The optimal cutoff value for CCR was 69.775 for male and 63.365 for female, with areas under the ROC curve of 0.639 for male and 0.648 for female. Postprandial blood glucose and CCR were independent risk factors, whereas age and postprandial C-peptide were independent protective factors for the KPD. Conclusion:High levels of CCR are significantly associated with the odds of KPD, suggesting that higher muscle mass (estimated by CCR) may be linked to higher KPD incidence. Our study suggests that CCR may be a useful marker for the incidence of KPD, providing new insights into the mechanisms of KPD.

AIMS:Prediabetes affects 35% of Chinese adults and is associated with increased risks of cardiovascular disease and mortality. However, findings are inconsistent on the effects of lifestyle and pharmacological interventions in the prediabetes population achieving remission. This analysis aimed to compare the effects of metformin plus lifestyle intervention versus lifestyle intervention alone for prediabetes remission. MATERIALS AND METHODS:This was a secondary analysis of the China Diabetes Prevention Program (CDPP), a multicentre unblinded randomised controlled trial of 1678 participants aged 18-70 years with impaired glucose regulation from 43 hospitals across China (NCT03441750). Participants were randomly assigned (1:1) using block randomisation stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), presence of hypertension and use of anti-hypertensive medication. They received either metformin plus lifestyle intervention or lifestyle intervention alone for 2 years. The primary outcome was prediabetes remission rate. RESULTS:During a median follow-up of 2.03 years, remission was achieved in 262/831 (31.5%) (138/396 men; 124/435 women) participants in the metformin plus lifestyle group versus 213/847 (25.1%) (106/397 men; 107/450 women) in the lifestyle alone group, with similar effects across subgroups. After adjusting for baseline characteristics, addition of metformin increased the rate of remission (HR 1.39, 95% CI 1.16-1.67, p < 0.001). Higher baseline HbA1c was associated with lower remission rates (HR 0.23, 95% CI 0.18-0.29, p < 0.001). CONCLUSIONS:Adding metformin to a lifestyle intervention significantly improved prediabetes remission rates over lifestyle intervention alone in Chinese adults with impaired glucose regulation. This may be an effective approach for prediabetes management.

BACKGROUND:Polycystic ovary syndrome (PCOS) is a neuroendocrine-metabolic disorder with no approved drugs. Hypothalamic-pituitary-ovarian (HPO) axis dysfunction is core pathogenesis, and metabolic heterogeneity complicates treatment. Existing medications rarely ameliorate PCOS comprehensively. Sangzhi alkaloids (SZ-A), an extract from Morus alba L. twigs approved for type 2 diabetes in China, have not been systematically explored for PCOS. PURPOSE:To clarify the therapeutic effect and the mechanisms of SZ-A in PCOS. STUDY DESIGN:Animal studies, in vitro experiments and a placebo-controlled clinical trial. MATERIALS AND METHODS:In vivo: Obese/non-obese PCOS rats received oral SZ-A 67, 100, 150 mg/(kg·d) for 21 days (positive controls: Diane-35, metformin). In vitro: Granulosa cell apoptosis induced by dihydrotestosterone was treated with SZ-A 25, 50, 100, 200 μg/ml. CLINICAL:6-month placebo-controlled trial (128 PCOS patients; oral SZ-A 300 mg/d, n = 88; placebo, n = 40). Multi-omics/Western blotting explored HPO pathways. RESULTS AND DISCUSSION:In rats, SZ-A (67 to 150 mg/(kg·d), 21 days) dose-dependently reduced androgens, regularized estrous cycles, and improved ovarian morphology. In vitro, SZ-A (25 to 200 μg/ml) protected granulosa cells from apoptosis. In patients, 6-month SZ-A (300 mg/d) lowered free androgen index and improved menstrual regularity versus placebo. Mechanistically, SZ-A inhibited hyperandrogenism-induced granulosa cell apoptosis and regulated GnRH secretion and downstream signaling pathways. CONCLUSION:SZ-A exerts therapeutic effects on PCOS by modulating HPO axis function through multiple pathways. TRIAL REGISTRATION:ChiCTR2200065097.

Introduction:The combination of dapagliflozin and metformin is commonly used as an initial therapy for patients with type 2 diabetes mellitus (T2DM) with high glycated hemoglobin (HbA1c) levels. Although bioequivalence has been established for the fixed-dose combination (FDC) of dapagliflozin/metformin extended-release (XR) compared to the co-administration of dapagliflozin and metformin XR, it remains uncertain whether the efficacy of dapagliflozin/metformin FDC is comparable to that of co-administration. Additionally, it is still unclear whether fixed-dose combinations offer advantages in terms of patient adherence and satisfaction. This study aims to compare the dapagliflozin/metformin XR FDC with co-administration of dapagliflozin and metformin XR for efficacy in terms of glycemic control, patient satisfaction, quality of life and adherence in Chinese patients with newly diagnosed T2DM. Methods and analysis:This multicenter, randomized, non-inferiority, open-label clinical trial enrolled 632 patients with T2DM (HbA1c 7.5-10%) in 35 research centers in China. After enrollment, the patients will be randomly assigned to receive either FDC treatment (10 mg dapagliflozin and 1000 mg metformin XR) or co-administered 10 mg dapagliflozin and 1000 mg metformin XR tablets for 24 weeks. The primary endpoint was the change in HbA1c level from baseline after 24 weeks of treatment. Secondary endpoints included the proportion of patients achieving HbA1c below 7.0%, absolute changes in fasting plasma glucose and postprandial glucose from baseline to week 24, the difference in patient satisfaction measured with the diabetes treatment satisfaction questionnaire, medication usage measured with adherence to refills and medications scale for diabetes between the two groups at week 24, change from baseline in diabetes quality of life questionnaire score at week 12 and week 24, and safety. Continuous glucose monitoring will also be used to evaluate the benefits of FDC compared with co-administration on glycemic variability. Discussion:This study, as the first of its kind, will provide comparative data on the efficacy of the dapagliflozin/metformin XR FDC and co-administration of dapagliflozin and metformin XR in terms of glycemic control, patient satisfaction, quality of life and adherence. These data will help clinicians make more informed decisions for patients with type 2 diabetes and may improve medication burden, treatment adherence, and satisfaction.

BACKGROUND Increased blood urea nitrogen (BUN) levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes (T2D), potentially playing a role in the development of diabetic complications, including diabetic peripheral neuropathy. AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D. METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured. Electromyography was used to assess peripheral motor and sensory nerve function in all patients, and overall composite Z -scores were subsequently calculated for nerve latency, amplitude, and conduction velocity (NCV) across the median, ulnar, common peroneal, posterior tibial, superficial peroneal, and sural nerves. RESULTS Across the quartiles of BUN levels, the overall composite Z -score for latency (F = 38.996, P for trend < 0.001) showed a significant increasing trend, whereas the overall composite Z -scores for amplitude (F = 50.972, P for trend < 0.001) and NCV (F = 30.636, P for trend < 0.001) exhibited a significant decreasing trend. Moreover, the BUN levels were closely correlated with the latency, amplitude, and NCV of each peripheral nerve. Furthermore, multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z -score for latency (β = 0.166, t = 3.864, P < 0.001) and lower overall composite Z-scores for amplitude (β = -0.184, t = -4.577, P < 0.001) and NCV (β = -0.117, t = -2.787, P = 0.006) independent of the estimated glomerular filtration rate and other clinical covariates. Additionally, when the analysis was restricted to sensory or motor nerves, elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction. CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.

Ferroptosis and insulin resistance (IR) play crucial roles in the development of gestational diabetes mellitus (GDM). This study aims to analyze the effects of perillaldehyde (PAE) on ferroptosis and IR in human trophoblast cells, as well as its underlying mechanism in these effects. In this study, human trophoblasts (HTR-8/SVneo cells) treated with high glucose or in combination with insulin were used as in vitro models of GDM. The protective effects of PAE were evaluated by detecting insulin resistance and ferroptosis. GSE datasets (GSE154414 and GSE54157), SwissTargetPrediction, and GeneCards were used for gene target prediction. Results showed that PAE mitigated the decrease in HTR-8/SVneo cell viability caused by HG treatment. PAE exerted a protective effect against HG-triggered ferroptosis in HTR-8/SVneo cells by reducing ROS, Fe2+, and MDA levels, while increasing GSH and GPX4 levels and SOD activity. PAE alleviated IR in HTR-8/SVneo cells by increasing IRS1 and GLUT4 mRNA levels and glucose uptake, while decreasing IGF-1 mRNA level. PAE inhibited the expression of PTPN1 in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression reversed the effect of PAE on ferroptosis in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression counteracted the effects of PAE on IR in HTR-8/SVneo cells. PAE activated the Akt/Foxo signaling pathway by downregulating PTPN1 in HTR-8/SVneo cells under HG conditions. Akt/Foxo1 activation counteracted the effects of PTPN1 overexpression on ferroptosis and IR in HTR-8/SVneo cells with HG treatment. In conclusion, PAE attenuated IR and high glucose-triggered ferroptosis in trophoblast cells via regulation of the PTPN1/Akt/Foxo1 signaling pathway.

Saturated fatty acid (SFA) accumulation in liver decreases hepatocyte lipophagy, a type of selective autophagy that degrades intracellular lipid droplets, leading to hepatic insulin resistance (IR), which contributes to simultaneous increases in liver glucose production and fat synthesis, resulting in hyperglycemia and dyslipidemia traits of type 2 diabetes mellitus (T2DM). Stromal cell derived factor-1 (SDF-1), a cytokine produced by hepatocytes, inhibits autophagy. In this study, we evaluated the hypothesis that SDF-1 promoted hepatic IR via inhibiting hepatocyte lipophagy during T2DM. Furthermore, we probed the downstream pathway participating in the role of SDF-1. The results showed that the neutralising of SDF-1 improved hepatic IR via promoting hepatocyte lipophagy in a mouse high-fat and high sucrose diet (HFHSD)-induced T2DM model. In vitro, SDF-1 expression and release increased in palmitic acid (PA, a kind of SFA)-treated hepatocytes. Meanwhile, SDF-1 bound to up-regulated C-X-C chemokine receptor type 4 (CXCR4) and C-X-C chemokine receptor type 7 (CXCR7) on PA-treated hepatocytes. Subsequently, SDF-1 inhibited lipophagy in PA-treated hepatocytes via CXCR4, rather than CXCR7. Finally, SDF-1/CXCR4/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-inhibited lipophagy promotes PA-induced hepatocyte IR. Collectively, this study discovered that SDF-1 might inhibit lipophagy in SFA-treated hepatocytes to promote hepatic IR via CXCR4/AKT/mTOR pathway.

This study investigated the correlation between glucose time-in-range (TIR) and hepatic steatosis severity or liver fibrosis risk in Chinese adults with type 2 diabetes mellitus (T2DM) comorbid with metabolic dysfunction-associated steatotic liver disease (MASLD). Participants with T2DM were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. TIR was calculated based on data from a retrospective continuous glucose monitoring system. A total of 184 T2DM patients with MASLD were enrolled. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) decreased with increasing TIR (p < 0.05). Spearman correlation showed negative correlations between CAP, LSM, and TIR (r = -0.824 and − 0.842, p < 0.05) and positive correlations with basal insulin resistance (HOMA-IR) (r = 0.205 and 0.208, p < 0.01). Multiple linear regression revealed TIR and HOMA-IR independently correlated with CAP (std. regression coefficients = -0.695 and 0.103, p < 0.05) and LSM (std. regression coefficients = -0.735 and 0.083, p < 0.05), wit0.34 h TIR having a stronger impact. Binary logistic regression showed TIR Groups 3 (70

ObjectiveEnergy homeostasis is modulated by the hypothalamic is essential for obesity progression, however, the gene expression profiling remains to be fully understood.MethodsGEO datasets were downloaded from the GEO website and analyzed by the R packages to obtain the DEGs. And, the WGCNA analysis and PPI networks of co-expressed DEGs were designed using STRING to get key genes. In addition, the single-cell sequencing datasets and GTEx database were utilized to receive the neuron-stress genes from the key genes. Further, high-fat diet (HFD)-induced hypothalamic tissue of mice was used as an animal model to validate the mRNA up-regulation of neuron-stress genes. In addition, the Bmi1 gene was identified as a hub gene through the LASSO model and nomogram analysis. Western blot confirmed the high expression of Bmi1 in hypothalamic tissue of HFD mice and PA-stimulated microglia. Immunofluorescence staining showed that HFD induced the activation of microglia and the expression of Bmi1 in hypothalamic tissue.ResultsWe found that six genes (Sacm1l, Junb, Bmi1, Erbb4, Dkc1, and Suv39h1) are neuron stress-related genes and increased in the HFD-induced mice obesity model, Bmi1gene was identified as a key genes that can reflect the pathophysiology of obesity.ConclusionsOur research depicted a comprehensive activation map of cell abnormality in the obese hypothalamus and Bim1 may be a diagnostic marker in the clinic, which provides a new perspective and basis for investigating the pathogenesis of obesity.

BACKGROUND:This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS:A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS:There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION:Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

BACKGROUND:Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity.METHODS:We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro.RESULTS:The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model.CONCLUSION:Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.

Abstract Background Impaired thyroid hormone sensitivity has been associated with type 2 diabetes (T2D), obesity, and metabolic syndrome, which can lead to alterations of body composition. However, impaired thyroid sensitivity to exacerbate alterations of body composition remains unconfirmed. This study aimed to ascertain impaired thyroid hormone sensitivity association with body composition in euthyroid T2D. Methods A total of 634 individuals with normothyroid T2D were enrolled. Each participant underwent a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, including measurements of body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD), and total BMD (T-BMD). Thyroid hormone resistance indices were assessed by calculating serum thyrotropin (TSH) index (TSHI), thyrotrophin T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric TFQI (PTFQI). Relevant clinical data was also collected. Results Among the recruited patients, females (n = 265) had higher indicators of thyroid hormone resistance and fat distribution than males (n = 369) (all P < 0.05). Across the entire population, indicators of thyroid hormone resistance exhibited positive correlations with fat distribution (all P < 0.01), while most indicators displayed negative associations with skeletal muscle mass. These findings were consistent solely among male participants. Furthermore, even after adjusting for basic characteristics, linear regression analysis revealed that these correlations remained statistically significant (all P < 0.05). Conclusions In males with euthyroid T2D, impaired thyroid hormone sensitivity correlates with fat distribution independent of conventional risk factors.

A variety of diseases are often observed during pregnancy and miR-190b involves in gestational diabetes mellitus (GDM). This study assesses miR-190b’s role in GDM. Electron microscopy analyzed the size of nanoparticles. miR-190b expression in tissues was detected and its effects on islet cells were detected by MTT method, BrdU staining method and ELISA method. Insulin secretion was further detected by molecular biology techniques. Electron microscopy showed similar average particle size of each formulation. miR-190b was overexpressed in the placental tissues of GDM and its overexpression promoted cell proliferation and insulin secretion, whereas downregulation of miR-190b exerted opposite effects. In addition, miR-190b negatively modulated NKX6-1 level and their relationship was confirmed by bioinformatics techniques and a luciferase reporter gene. NKX6-1 overexpression reversed miR-190b mimics’ effect, and miR-190b knockdown promoted insulin secretion by upregulating NKX6-1. The inhibitory effect of miR-190b overexpression on islet β cells using nano-albumin particles as a carrier was partially reversed by NKX6-1 overexpression. Silencing of miR-190b by nano-albumin particles as a carrier promoted β-cell function, which may be one of the mechanisms by which miR-190b affects GDM.

Background Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. Methods The National Health and Nutrition Examination Survey (2013–2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 were the specific diagnostic criteria for DKD. Results In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably ( P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. Conclusions A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.

BACKGROUND:This study aims to examine the alterations and clinical significance of CD8+ regulatory T cell subsets in the peripheral blood of individuals with type 1 diabetes mellitus (T1DM). METHODS:From January 2020 to December 2023, a study was conducted involving 40 individuals with T1DM, who visited the Department of Endocrinology at the First Affiliated Hospital of Nanjing Medical University (T1DM group). For comparison, 40 healthy individuals who underwent routine physical examinations at the same hospital during this period were selected as the control group. Peripheral blood mononuclear cells were isolated, and CD8+ T cells were labeled with CD3, CD25 and FoxP3 to analyze their subset frequencies using flow cytometry. The study examined differences in subset frequencies between the two groups and explored correlations between subset frequency, disease duration, and age of onset. RESULTS:The frequencies of CD8+ CD25+, CD8+ FoxP3+, CD8+ CD25+ CD3+ and CD8+ FoxP3+ CD3+ subsets in peripheral blood mononuclear cells did not significantly differ between the healthy control group and the T1DM group (P > 0.05). In the T1DM group, the expression level of CD25 on CD8+ T cells showed no correlation with the age of onset or disease duration, and FoxP3 levels were also unrelated to the age of onset, with no statistical differences (P > 0.05). However, within the T1DM group, FoxP3 levels progressively decreased with longer disease duration, demonstrating a statistically significant negative correlation (Pearson r = -0.331, P < 0.05). In the T1DM group, the level of CD3+ CD8+ T cells expressed CD25, and there was no correlation between Foxp 3 level and age of onset, not statistically significant (P > 0.05), but the level of Foxp 3 in the T1DM group decreased with the duration of the disease, (Pearson r= - 0.363, P < 0.05). CONCLUSION:The levels of CD8+FoxP3+ regulatory T cells in peripheral blood mononuclear cells of patients with T1DM show a significant correlation with disease duration, suggesting that these cells may play a critical role in the progression of T1DM.

While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer’s Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p < 0.001)] standardized score higher and a 0.07 (SE = 0.01; p < 0.001) standardized score higher cognitive score, whereas a higher hand grip strength was positively associated with a better cognitive performance. Reverse MR assessments also yielded similar findings. These data suggest that lower walking speed, muscle strength, and muscle mass were all closely related to lower cognitive performance irrespective of gender, and that there may be a mutually reinforcing relationship among these variables.

甲状腺激素(TH)是人体组织器官多重调节作用的一个重要组成部分,在维持血糖水平稳定,对循环胰岛素水平、肝脏糖原输出、中枢和外周组织葡萄糖摄取的调节等方面发挥着重要的作用.糖尿病与甲状腺功能异常是最常见的内分泌系统疾病,并且常共同存在,TH代谢与糖代谢彼此影响;而胰岛素敏感性下降是2型糖尿病早期表现,更贯穿于糖尿病发生和发展的全过程.TH代谢与胰岛素敏感性已成为研究热点,本文根据TH在代谢调节中的作用途径,综述其影响胰岛素敏感性的机制.

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness ( p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men ( p < .01), while they were insignificant in subgroups of elderly and non-elderly women ( p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031–1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.