Man Wu, Chaoyang Li, Yiqing Yu, Lijuan Zeng, Yufei Qiu, Jiali Liu, Fen Yang, Yangyang Han
{"title":"Association between the triglyceride-glucose (TyG) index and stroke risk in Chinese normal-weight adults: a population-based study.","authors":"Man Wu, Chaoyang Li, Yiqing Yu, Lijuan Zeng, Yufei Qiu, Jiali Liu, Fen Yang, Yangyang Han","doi":"10.1186/s13098-024-01421-w","DOIUrl":"10.1186/s13098-024-01421-w","url":null,"abstract":"<p><strong>Background: </strong>Identifying high-risk populations and promoting stroke prevention measures can be achieved through studies on stroke and its risk factors. As a new alternative indicator of insulin resistance (IR), the triglyceride glucose (TyG) index may potentially increase stroke risk. However, the evidence confirming this association is inadequate and inconsistent, possibly due to variations in stroke assessment criteria or characteristics of the study populations. This study aims to evaluate the association between the TyG index and stroke risk level among individuals with normal-weight.</p><p><strong>Methods: </strong>A total of 30,895 participants aged ≥ 40 years with normal-weight were enrolled in this study. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Normal-weight was described as a body mass index (BMI) of 18.5-<24.0 kg/m<sup>2</sup>. Stroke risk was assessed by the Stroke Risk Assessment Scale, developed by the China National Stroke Screening and Prevention Project. To evaluate the associations between the TyG index and stroke risk level, multivariate logistic regression models were employed.</p><p><strong>Results: </strong>Results showed that when the TyG index was considered as a continuous variable, each one unit increase in the TyG index was associated with a significantly higher risk of stroke [Moderate-risk (OR, 2.15; 95% CI, 2.03-2.28; P<0.001); High-risk (OR, 3.83; 95% CI, 3.57-4.10; P<0.001)]. Compared with Q1 of the TyG index, Q4 was significantly associated with moderate stroke risk (OR, 2.73; 95% CI, 2.50-2.99; P<0.001) and high stroke risk (OR, 5.39; 95% CI, 4.83-6.01; P<0.001). The continuous TyG index was an important risk factor for high stroke risk in the metabolically obese, normal-weight (MONW) individuals (OR, 3.44;95% CI, 2.92-4.06; P < 0.001). In the MONW individuals, when Q1 was used as a reference, participants in Q4 (OR, 5.33; 95% CI, 4.19-6.78; P < 0.001) was significantly associated with high stroke risk. Subgroup analysis showed significant interaction in the age and sex subgroups in the overall population (P<sub>interaction</sub> <0.001).</p><p><strong>Conclusion: </strong>The risk of stroke is increased with the TyG index among Chinese adults of normal weight; hence, the index may be an important indicator for identifying high-risk stroke populations among individuals with normal body weight.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L M Pechmann, F I Pinheiro, V F C Andrade, C A Moreira
{"title":"The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review.","authors":"L M Pechmann, F I Pinheiro, V F C Andrade, C A Moreira","doi":"10.1186/s13098-024-01412-x","DOIUrl":"10.1186/s13098-024-01412-x","url":null,"abstract":"<p><strong>Background: </strong>Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures.</p><p><strong>Main body: </strong>The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals.</p><p><strong>Conclusion: </strong>The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"\"Adjusting internal organs and dredging channelon\" electroacupuncture glycolipid metabolism disorders in NAFLD mice by mediating the AMPK/ACC signaling pathway.","authors":"Xinyu Jia, Mengyuan Li, Wen Zhang, Yihui Guo, Fuyu Xue, Shiqi Ma, Shuo Yu, Zhen Zhong, Haipeng Huang","doi":"10.1186/s13098-024-01416-7","DOIUrl":"10.1186/s13098-024-01416-7","url":null,"abstract":"<p><p>To investigate the effect mechanism of electroacupuncture based on the AMP-activated protein kinase (AMPK) /acetyl-CoA carboxylase (ACC) signaling pathway to improve glycolipid metabolism disorders in db/db mice. 10 db/m mice with normal genotype were used as the normal control group without diabetes (Con), and 30 db/db mice were divided randomly into three groups: Pathological model mice (Mod), Acupuncture + ACC antagonist group (Acu + ACC), and Acupuncture + AMPK antagonist group (Acu + AMPK). Con and Mod did not receive any special treatment, only as a control observation. The latter two groups of mice received electroacupuncture treatment for 4 weeks. Mouse triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C), and cholesterin(CHO) levels were detected by colorimetric assay. Enzyme-linked immunoassay (ELISA) was used to detect insulin(INS) levels. Liver histopathologic changes and hepatic glycogen synthesis were observed by HE and PAS staining. The mRNA and protein expression of insulin receptor substrate-1(IRS1), Phosphatidylinositol 3-kinase(PI3K), protein kinase B (AKT), AMPK, and ACC were detected by Western blot and qRT-PCR.The results show that compared with Mod, TG, LDL, CHO, and INS levels of Acu + AMPK and Acu + ACC mice were significantly reduced (P < 0.05), and the HDL levels were significantly increased (P < 0.05), the steatotic degeneration of mice hepatocytes was reduced to different degrees, and the hepatocyte glycogen particles were increased, and the latter two groups had a decrease in AKT, ACC mRNA expression was reduced (P < 0.05), PI3K protein expression was increased, and AKT and ACC protein expression was reduced (P < 0.05), in addition, protein expression of AMPK was increased and IRS1 protein expression was reduced in Acu + ACC (P < 0.05). The study showed that electroacupuncture improves glucose-lipid metabolism disorders in db/db mice, and this mechanism is related to the AMPK/ACC signaling pathway.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aled Wyn Jones, Abraham Makanjuola, Nathan Bray, Yeliz Prior, Daniel Parker, Christopher Nester, Jinghua Tang, Liudi Jiang
{"title":"The efficacy of custom-made offloading devices for diabetic foot ulcer prevention: a systematic review.","authors":"Aled Wyn Jones, Abraham Makanjuola, Nathan Bray, Yeliz Prior, Daniel Parker, Christopher Nester, Jinghua Tang, Liudi Jiang","doi":"10.1186/s13098-024-01392-y","DOIUrl":"10.1186/s13098-024-01392-y","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic offloading devices, including insoles, shoes, and other orthoses, are some of the most commonly used interventions to treat or prevent diabetic foot ulceration. Custom-made offloading devices are increasingly used to offset the development of foot ulcers. However, whether these devices are more effective than prefabricated standard offloading devices is uncertain. Therefore, this systematic review collates and examines evidence on the efficacy of custom-made offloading devices in preventing foot ulcer incidence and recurrence in people diagnosed with diabetes.</p><p><strong>Methods: </strong>Five scientific databases were searched, covering 2011-2023. Initial searches and screening were carried out independently by two researchers. Studies meeting the inclusion criteria were further examined through additional screenings, and critical appraisal. Data relevant to the review aims were extracted and analysed within a narrative synthesis.</p><p><strong>Results: </strong>Of the 1,715 articles found in the initial searches, nine papers were found to meet inclusion criteria and were included in the review. The evidence shows that custom-made offloading devices are likely to be more effective for reducing or preventing diabetic foot ulcers than standard offloading devices. However, due to a lack of data it remains uncertain whether custom-made offloading devices are more cost-effective for preventing ulceration compared to standard insoles. Likewise, due to measurement heterogeneity between studies and lack of data, it is unclear whether adherence is higher in users of custom-made offloading devices, and whether such devices deliver significantly greater reductions in peak pressure as compared to standard offloading devices.</p><p><strong>Conclusion: </strong>Custom-made offloading devices are more effective than standard devices for preventing diabetic foot ulceration, and we recommended their use when feasible; however, there remains uncertainty regarding their cost-effectiveness compared to standard insoles and offloading devices.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Independent effects of the glucose-to-glycated hemoglobin ratio on mortality in critically ill patients with atrial fibrillation","authors":"Yuqing Fu, Xing Wei, Cong Xu, Guifu Wu","doi":"10.1186/s13098-024-01401-0","DOIUrl":"https://doi.org/10.1186/s13098-024-01401-0","url":null,"abstract":"The glucose-to-glycated hemoglobin ratio (GAR) represents stress hyperglycemia, which has been closely associated with adverse outcomes in cardio-cerebrovascular diseases. No studies have examined the association between stress hyperglycemia and atrial fibrillation (AF) in critically ill patients. This study aims to explore the relationship between GAR and the prognosis of critically ill patients with AF. A retrospective cohort of patients was selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The GAR was calculated based on fasting blood glucose and glycated hemoglobin levels measured after admission. The primary outcome was the 30-day mortality rate, with secondary outcomes being the 90-day and 365-day mortality rates. The GAR was divided into tertiles, and Kaplan–Meier analysis was employed to compare differences in mortality rates between groups. The Cox proportional hazards model and restricted cubic splines (RCS) were utilized to evaluate the relationship between the GAR and mortality. Subsequently, a segmented regression model was constructed to analyze threshold effects in cases where nonlinear relationships were determined. In this cohort, the second tertile of the GAR exhibited lower mortality rates at 30 days (10.56% vs 6.33% vs 14.51%), 90 days (17.11% vs 10.09% vs 17.88%), and 365 days (25.30% vs 16.15% vs 22.72%). In the third tertile, the risk of mortality at 30 days increased by 165% (HR = 2.65, 95% CI 1.99–3.54, p < 0.001), at 90 days increased by 113% (HR = 2.13, 95% CI 1.68–2.70, p < 0.001), and at 365 days increased by 70% (HR = 1.70, 95% CI 1.68–2.70, p < 0.001). The association between the GAR and patient mortality demonstrated a “J-shaped” non-linear correlation. Once the GAR exceeded 15.915, each incremental unit increase in the ratio was associated with a 27.2% increase in the risk of 30-day mortality in critically ill atrial fibrillation patients (HR = 1.262, 95% CI 1.214–1.333, p < 0.001). The GAR is associated with both short-term and long-term mortality in critically ill patients with AF in a J-shaped relationship. Both low and excessively high GAR values indicate poor prognosis.","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141737850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong-Da Zhang, Lei Ding, Li-Jie Mi, Ai-Kai Zhang, Yuan-Dong Liu, Fu-Hua Peng, Xin-Xin Yan, Yu-Jing Shen, Min Tang
{"title":"Joint effect of atrial fibrillation and obesity on mortality in critically ill patients.","authors":"Hong-Da Zhang, Lei Ding, Li-Jie Mi, Ai-Kai Zhang, Yuan-Dong Liu, Fu-Hua Peng, Xin-Xin Yan, Yu-Jing Shen, Min Tang","doi":"10.1186/s13098-024-01407-8","DOIUrl":"10.1186/s13098-024-01407-8","url":null,"abstract":"<p><strong>Background: </strong>The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population.</p><p><strong>Methods: </strong>Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods.</p><p><strong>Results: </strong>The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF.</p><p><strong>Conclusions: </strong>AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yang, Jie Wang, Yi Huang, Yuhang Liu, Shuwan Liu, Huabao Liu, Meiao Tan
{"title":"Association between sex hormone binding globulin and metabolic syndrome in US adults: insights from National Health and Nutrition Examination Survey (NHANES) 2013-2016.","authors":"Yang Yang, Jie Wang, Yi Huang, Yuhang Liu, Shuwan Liu, Huabao Liu, Meiao Tan","doi":"10.1186/s13098-024-01398-6","DOIUrl":"10.1186/s13098-024-01398-6","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome (MetS) presents a notable public health challenge on a global scale, exerting a considerable impact on individuals' health and quality of life. There is mounting evidence indicating a robust association between MetS and levels of sex hormones. Therefore, the study aims to explore the relationship between sex hormone binding-globulin (SHBG) and MetS, and to provide evidence that could inform the development of effective prevention strategies for MetS.</p><p><strong>Methods: </strong>Data for this cross-sectional investigation were collected during the 2013-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), from which 5,499 adults were sampled. The criteria established by the Adult Treatment Program III of the National Cholesterol Education Program were utilized to define MetS. SHBG levels were measured using a standardized technique. Multivariate-adjusted logistic regression, multivariate restricted cubic spline, and threshold effect analyses were utilized to investigate the association between SHBG levels and MetS. Moreover, the stratified analyses and interaction tests of covariables were presented in a forest plot. Finally, sensitivity analysis was utilized to ensure the robustness of the results.</p><p><strong>Results: </strong>Overall, 1822 participants had MetS. After adjusting for possible confounders, SHBG levels were associated with MetS (Odds ratio [OR], 0.984; 95% confidence interval [CI], 0.981-0.986; P < 0.01). The multivariate restricted cubic spline analysis demonstrated a non-linear association between SHBG and MetS (P < 0.001). With two piecewise regression models, the adjusted OR of developing MetS was 0.964 (95% CI, 0.959-0.969; P < 0.001) among people with SHBG < 76.653 nmol/L, but there was no correlation between SHBG and MetS in participants with SHBG ≥ 76.653 nmol/L. The stability of the association between SHBG levels and MetS was confirmed using subgroup analysis and sensitivity analyses.</p><p><strong>Conclusions: </strong>Our results suggest that reduced SHBG levels are associated with an increased prevalence of MetS in adults, particularly when SHBG levels are below 76.653 nmol/L. More investigation is required to understand comprehend the mechanisms underlying these results and to delve into their clinical implications.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The U-shape relationship between insulin resistance-related indexes and chronic kidney disease: a retrospective cohort study from National Health and Nutrition Examination Survey 2007-2016.","authors":"Ruihua Shen, Ling Lin, Zexuan Bin, Xi Qiao","doi":"10.1186/s13098-024-01408-7","DOIUrl":"10.1186/s13098-024-01408-7","url":null,"abstract":"<p><strong>Background: </strong>There is ongoing debate on the correlation between chronic kidney disease (CKD) and insulin resistance (IR)-related indices. Our objective was to explore the prognostic ability of IR-related indexes for the prevalence of CKD, as well as the mortality from all causes and cardiovascular disease (CVD) in CKD patients.</p><p><strong>Methods: </strong>The data used in this study came from the National Health and Nutrition Examination Survey (NHANES). Binary logistic regression analysis, Cox proportional hazards model, and restricted cubic spline (RCS) were used to analyze the relationship between IR-related indexes, including metabolic score of IR (METS-IR), homeostatic model assessment for IR (HOMA-IR), triglyceride glucose index (TyG), triglyceride glucose-waist-to-height ratio (TyG-WHtR), triglyceride glucose-body mass index (TyG-BMI), with CKD and its all-cause mortality and CVD mortality. Subgroup analysis was performed to test the stability of the results. Finally, the predictive power of IR-related indexes for CKD was tested by the receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>Among the recruited 10,660 participants, 15.42% were CKD patients. All IR-related indexes were found to be nonlinearly correlated to the prevalence of CKD in the study. When the TyG index was higher than 9.05, it was positively associated with CKD (OR: 1.77, 95% CI 1.44-2.18). Moreover, increased TyG-WHtR level was correlated with a greater prevalence of CKD when it was higher than 4.3 (OR: 1.31, 95% CI 1.19-1.45). Other IR-related indexes (METS-IR, HOMA-IR, and TyG-BMI) showed fewer notable correlations with CKD. The association of IR-related indexes and the prevalence of CKD remained consistent in most subgroups (P for interactions > 0.05). TyG-WHtR was also the predictor of all-cause mortality in CKD patients (HR: 1.34, 95% CI 1.14-1.58), while other IR-related indexes were not correlated with the all-cause mortality or CVD mortality in CKD patients (P > 0.05). Otherwise, ROC curves showed that TyG-WHtR had more robust diagnostic efficacy than other IR-related indexes (METS-IR, HOMA-IR, TyG, and TyG-BMI) in predicting CKD (area under the curve: 0.630, 95% CI 0.615-0.644).</p><p><strong>Conclusions: </strong>IR-related biomarkers (METS-IR, HOMA-IR, TyG, and TyG-BMI) were positively correlated with the prevalence of CKD. Moreover, TyG-WHtR enhanced CKD and its all-cause mortality prediction. In patients with elevated levels of IR-related indexes, the early detection and intervention of IR may reduce the occurrence of CKD and the prognosis of CKD patients.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RUNX3-activated apelin signaling inhibits cell proliferation and fibrosis in diabetic nephropathy by regulation of the SIRT1/FOXO pathway.","authors":"Xin Zhong, Jun Zhang","doi":"10.1186/s13098-024-01393-x","DOIUrl":"10.1186/s13098-024-01393-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy is a major secondary cause of end-stage renal disease. Apelin plays an important role in the development of DN. Understanding the exact mechanism of Apelin can help expand the means of treating DN.</p><p><strong>Methods: </strong>Male C57BL/6 mice was used and STZ treatment was implemented for DN model establishment. Lentivirus systems including Lv-sh-RUNX3 and Lv-Apelin were obtained to knockdown RUNX3 and overexpress Apelin, respectively. A total of 36 mice were divided into 6 groups (n = 6 in each group): control, DN, DN + LV-Vector, DN + Lv-Apelin, DN + LV-Apelin + LV-sh-NC and DN + Lv-Apelin + Lv-sh-RUNX3 group. In vitro studies were performed using mesangial cells. Cell viability and proliferation was assessed through CCK8 and EDU analysis. Hematoxylin and eosin staining as well as Masson staining was implemented for histological evaluation. RT-qPCR was conducted for measuring relative mRNA levels, and protein expression was detected by western blotting. The interaction between SIRT1 and FOXO were verified by co-immunoprecipitations, and relations between RUNX3 and Apelin were demonstrated by dual luciferase report and chromatin immunoprecipitation.</p><p><strong>Results: </strong>The DN group exhibited significantly lower Apelin expression compared to control (p < 0.05). Apelin overexpression markedly improved blood glucose, renal function indicators, ameliorated renal fibrosis and reduced fibrotic factor expression (p < 0.05) in the DN group, accompanied by elevated sirt1 levels and diminished acetylated FOXO1/FOXO3a (p < 0.05). However, RUNX3 knockdown combined with Apelin overexpression abrogated these beneficial effects, leading to impaired renal function, exacerbated fibrosis, increased fibrotic factor expression and acetylated FOXO1/FOXO3a versus Apelin overexpression alone (p < 0.05). In mesangial cells under high glucose, Apelin overexpression significantly inhibited cell proliferation and fibrotic factor production (p < 0.05). Conversely, RUNX3 interference enhanced cell proliferation and the secretion of fibrotic factors. (p < 0.05). Remarkably, combining Apelin overexpression with RUNX3 interference reversed the proliferation and fibrosis induced by RUNX3 interference (p < 0.05). Mechanistic studies revealed RUNX3 binds to the Apelin promoter, with the 467-489 bp site1 as the primary binding region, and SIRT1 physically interacts with FOXO1 and FOXO3a in mesangial cells.</p><p><strong>Conclusion: </strong>RUNX3 activated Apelin and regulated the SIRT1/FOXO signaling pathway, resulting in the suppressed cell proliferation and fibrosis in diabetic nephropathy. Apelin is a promising endogenous therapeutic target for anti-renal injury and anti-fibrosis in diabetic nephropathy. RUNX3 may serve as an endogenous intervention target for diseases related to Apelin deficiency.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evdokia Nikolaou, Maria Tziastoudi, Sofia G Gougoura, Georgios Filippidis, Periklis Dousdampanis, Alexandra Bargiota, Peter Rene Mertens, Theodoros Eleftheriadis, Georgios M Hadjigeorgiou, Georgios N Koukoulis, Ioannis Stefanidis
{"title":"Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis.","authors":"Evdokia Nikolaou, Maria Tziastoudi, Sofia G Gougoura, Georgios Filippidis, Periklis Dousdampanis, Alexandra Bargiota, Peter Rene Mertens, Theodoros Eleftheriadis, Georgios M Hadjigeorgiou, Georgios N Koukoulis, Ioannis Stefanidis","doi":"10.1186/s13098-024-01406-9","DOIUrl":"10.1186/s13098-024-01406-9","url":null,"abstract":"<p><strong>Background: </strong>In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.</p><p><strong>Methods: </strong>In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m<sup>2</sup>) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.</p><p><strong>Results: </strong>27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.</p><p><strong>Conclusions: </strong>Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}