Frontiers in Endocrinology最新文献

According to the Society of Critical Care Medicine, critical illness-related corticosteroid insufficiency (CIRCI) characterizes hypothalamic-adrenal axis insufficiency following acute medical conditions of various causes, i.e., sepsis, septic shock, acute respiratory distress syndrome, community-acquired pneumonia, and status after major surgical procedures. Due to highly variable etiology, understanding the pathomechanism and management of CIRCI assumes relevance for all centers providing intensive care. During CIRCI, multiple peripheral adaptations develop, and cortisol distribution volume increases due to hypothalamic-adrenal axis dysregulation, alterations in cortisol metabolism, and tissue resistance to corticosteroids. The proper diagnosis and treatment of CIRCI may be challenging in many cases. Although we have been acquainted with CIRCI since 2008, it remains a difficult condition with widely variable approaches among clinicians due to inconsistent high-quality study results determining the effect of corticosteroids on mortality. Corticosteroids are widely used in acutely ill patients, highlighting the necessity for reliable knowledge to support crucial clinicians' decisions in daily medical practice. In this review, we provide an overview of the clinical management of patients with CIRCI based on current recommendations and selected studies.

Background: Observational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomization (TSMR) method.

Methods: Genetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensitivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform.

Results: For forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs.

Discussion: This MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor.

Background: Few studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture.

Purpose: To compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures.

Methods: We recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration.

Results: Patients with multiple vertebral fractures had lower hip BMD (p=0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures (p=0.006). Diabetes was significantly more common in patients with multiple fractures (p=0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p<0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016-1.101; p=0.006) and low hip BMD (OR 0.016; 95% CI, 0.000-0.549; p=0.022) were associated with a higher risk of multiple fractures.

Conclusion: Patients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures.

Background: Anoikis is intricately associated with the malignant progression of cancer. Thyroid cancer (THCA) is the most common endocrine tumor, metastasis is closely related to treatment response and prognosis of THCA. Hence, it is imperative to comprehensively identify predictive prognostic genes and novel molecular targets for effective THCA therapy.

Methods: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to mine differentially expressed anoikis-related (DE-ARGs). Then, the prognostic genes were identified and a risk signature was constructed for THCA using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) method. Furthermore, the associations between risk signature and immune infiltration, immunotherapy, as well as potential mechanisms of action were determined using multiple R packages and Wilcoxon test. Finally, Mendelian randomized (MR) analysis was conducted to investigate the causal relationship between the prognostic genes and THCA.

Results: In total, six prognostic genes (LRRC75A, METTL7B, ADRA1B, TPD52L1, TNFRSF10C, and CXCL8) related to anoikis were identified, and the corresponding risk signature were constructed to assess the survival time of THCA patients. Immunocorrelation analysis demonstrated the anoikis-relevant risk signature could be used to evaluate immunotherapy effects in THCA patients, and the infiltration of immune cells was correlated with the degree of risk in THCA patients. According to two-sample MR analysis, there was the significant causal relationship between CXCL8 and THCA (odds ratio [OR] > 1 & p< 0.05), and the increase of its gene expression would lead to an increased risk of THCA. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) confirmed the upregulated expression patterns of these prognostic genes in THCA tissues.

Conclusion: In conclusion, we constructed the risk signature related to anoikis for THCA, which might have important clinical significance for improving the quality of life and treatment effect of THCA patients.

Purpose: Cancer often coexists with erectile dysfunction, yet the causal relationship between them remains unclear. This study aims to investigate the causal link between tumors and ED through Mendelian randomization.

Method: Data on 13 different cancers, including lung cancer, colorectal cancer, testicular cancer, lymphoma, esophageal cancer, pancreatic cancer, thyroid cancer, bladder cancer and brain cancer were collected from various databases. ED data, comprising 2,205 cases and 164,104 controls, were sourced from the FinnGen project. Primary methods for MR analysis included IVW, MR-Egger, weighted median, and weighted mode.

Results: IVW results revealed associations between colorectal cancer (OR=1.17;95% CI 1.02-1.13, p=0.0252), prostate cancer (OR=1.63;95% CI 1.52-1.75, p<0.001) and liver cancer (OR=0.93;95% CI 0.88 -0.99, p=0.012) with ED.

Conclusion: Mendelian randomization analysis supports that prostate cancer and colorectal cancer are associated with an increased risk of Erectile Dysfunction, whereas liver cancer is linked to a decreased risk of ED. No evidence suggests that ED contributes to an increased risk of prostate cancer.

[This corrects the article DOI: 10.3389/fendo.2024.1433930.].

Objective: This study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated.

Methods: This study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity.

Results: Among the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR (r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR (r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) (r = 0.224, P = 0.012), but negatively with eGFR (r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression (P<0.05). ROC analysis showed high predictive accuracy for DKD using these bone metabolism markers, with a combined area under the curve (AUC) of 0.846. Multivariate logistic regression analysis reinforced the significance of these markers in DKD progression.

Conclusion: Bone metabolism markers, such as klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS are intricately linked to DKD progression and may function as valuable predictive biomarkers.

Obesity significantly contributes to the progression of cardiovascular diseases (CVDs) and elevates the risk of cardiovascular mortality. Atherosclerosis, the primary pathogenic process underlying CVDs, initiates with vascular endothelial dysfunction, serving as the cornerstone of vascular lesions. Adipokines, bioactive molecules secreted by adipose tissue that regulate metabolic and endocrine functions, play a pivotal role in modulating endothelial function during atherosclerosis. This review comprehensively examines the distinct roles of various adipokines in regulating endothelial function in atherosclerosis. We categorize these adipokines into two main groups: protective adipokines, including adiponectin, FGF21, CTRP9, PGRN, Omentin, and Vaspin, and detrimental adipokines such as leptin, Chemerin, Resistin, FABP4, among others. Targeting specific adipokines holds promise for novel clinical interventions in the management of atherosclerosis-related CVDs, thereby providing a theoretical foundation for cardiovascular disease treatment strategies.

Introduction: Oxidative stress plays a crucial role in the development and progression of hyperuricemia/gout. This study aims to explore the relationship between the Oxidative Balance Score (OBS) and hyperuricemia/gout.

Methods: The study utilized complete data from adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2009 to 2018. OBS, composed of scores for 20 dietary and lifestyle factors, served as the exposure variable. Multivariable linear regression model was applied to evaluate the association between OBS and uric acid (UA). Multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) regression were conducted to explore the relationship between OBS and hyperuricemia/gout.

Results: A total of 18,998 participants were included. In the fully adjusted model, compared to the lowest quartile, the highest quartiles of OBS, dietary OBS, and lifestyle OBS were negatively correlated with UA (β=-0.31 (-0.36,-0.25), β=-0.18 (-0.24,-0.12), and β=-0.64 (-0.69,-0.59), respectively) and hyperuricemia (OR=0.63 (0.55,0.71), OR=0.76 (0.67,0.86), OR=0.37 (0.33,0.42), respectively). Moreover, the highest quartiles of OBS and lifestyle OBS exhibited a negative correlation with gout (OR=0.72(0.58,0.91), OR=0.54 (0.43,0.67), respectively). Subgroup analyses revealed differences in the negative association between OBS and hyperuricemia concerning hypertension (p for interaction =0.002) and diabetes (p for interaction= 0.004), while gender-related disparities were observed in the negative association between OBS and gout (p for interaction =0.008). RCS analysis demonstrated a linear negative association between hyperuricemia and OBS (p for non-linearity >0.05), while gout exhibited a non-linear negative association (p for non-linearity<0.05).

Conclusion: The study found that a higher OBS was associated with a decreased risk of developing hyperuricemia/gout, underscoring its potential in the prevention and management of these conditions.

Objective: Stroke risk factors often exert long-term effects, and Mendelian randomization (MR) offers significant advantages over traditional observational studies in evaluating the causal impact of these factors on stroke. This study aims to consolidate and evaluate the relationships between potential causal factors and stroke risk, drawing upon existing MR research.

Methods: A comprehensive search for MR studies related to stroke was conducted up to August 2023 using databases such as PubMed, Web of Science, Embase, and Scopus. This meta-analysis examines the relationships between potential causative factors and stroke risk. Both random-effects and fixed-effects models were utilized to compile the dominance ratios of various causative elements linked to stroke. The reliability of the included studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology incorporating Mendelian Randomization (STROBE-MR) guidelines.

Results: The analysis identified several risk factors for stroke, including obesity, hypertension, low-density lipoprotein cholesterol (LDL-C), chronic kidney disease (CKD), and smoking. Protective factors included high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), and educational attainment. Subgroup analysis revealed that type 2 diabetes mellitus (T2DM), diastolic blood pressure (DBP) are risk factors for ischemic stroke (IS).

Conclusion: This study confirms that variables such as obesity, hypertension, elevated LDL-C levels, CKD, and smoking are significantly linked to the development of stroke. Our findings provide new insights into genetic susceptibility and potential biological pathways involved in stroke development.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024503049.