Frontiers in Endocrinology最新文献

Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic metabolic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, and potentially liver cancer. This disease is closely associated with metabolic disorders driven by overnutrition, with key pathological processes including lipid dysregulation, impaired lipid autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and local inflammation. While hepatic lipid metabolism in NAFLD is well-documented, further research into inter-organ communication mechanisms is crucial for a deeper understanding of NAFLD progression. This review delves into intrahepatic networks and tissue-specific signaling mediators involved in NAFLD pathogenesis, emphasizing their impact on distal organs.

Objective: Previous observational studies suggest a potential link between gut microbiota, metabolites, and diabetic nephropathy. However, the exact causal relationship among these factors remains unclear.

Method: We conducted a two-sample bidirectional Mendelian randomization study using summary statistics from the IEU OpenGWAS Project database to investigate gut microbiota, metabolites, and diabetic nephropathy. A range of methods, including inverse variance weighting, MR-Egger, weighted median, and simple median, were applied to examine causal associations. Sensitivity analyses were performed to assess the robustness of the results. Additionally, reverse Mendelian randomization analysis was conducted, treating significant gut microbiota as the outcome, to evaluate effects and perform sensitivity testing. This comprehensive approach provided an in-depth assessment of the interactions among gut microbiota, metabolites, and diabetic nephropathy.

Result: The Inverse Variance Weighted estimates revealed that the abundance of Lachnospiraceae, Parasutterella, and Eubacterium exhibited negative causal effects on diabetic nephropathy, while Coprococcus, Sutterella, Faecalibacterium prausnitzii, and Bacteroides vulgatus showed protective causal effects against the condition. However, reverse Mendelian randomization analysis did not identify any significant associations between diabetic nephropathy and the identified gut microbiota. Furthermore, the estimates indicated that Cholesterol, Pyridoxate, Hexanoylcarnitine, X-12007, Octanoylcarnitine, 10-nonadecenoate (19:1n9), X-12734, and the average number of double bonds in a fatty acid chain had negative causal effects on diabetic nephropathy. In contrast, Methionine, Glycodeoxycholate, X-06351, 1-stearoylglycerol (1-monostearin), 5-dodecenoate (12:1n7), X-13859, 2-hydroxyglutarate, Glycoproteins, Phospholipids in IDL, and the concentration of small HDL particles demonstrated protective causal effects. Notably, sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy, ensuring the robustness of the findings.

Conclusion: Modulating gut microbiota diversity and composition offers a promising strategy for improving the incidence and prognosis of diabetic nephropathy. This highlights the need for future clinical trials focusing on microbiome-based interventions, potentially utilizing microbiome-dependent metabolites. Such approaches could transform the treatment and management of diabetic nephropathy and its associated risk factors, paving the way for more effective therapeutic strategies to combat this debilitating condition.

Background: Childhood autoimmune disorders involve the immune system attacking its own tissues, leading to varied symptoms, while autoinflammatory disorders result from innate immune system dysregulation, both requiring extensive diagnosis and multidisciplinary management due to their complexity.

Case presentation: We present a unique clinical case of a teenager with a combination of autoimmune and autoinflammatory disorders. The initial manifestation of hip pain, coupled with progressive symptoms over several years and findings in multiple magnetic resonance imaging (MRI) scans, culminated in the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Subsequently, the patient was diagnosed with type 1 diabetes (T1D), celiac disease, and juvenile idiopathic arthritis.The therapeutic course proved challenging, marked by unsuccessful attempts with nonsteroidal anti-inflammatory drugs (NSAIDs), and biphosphonates. However, a stable clinical status was ultimately achieved upon the introduction of methotrexate, concomitant with insulin therapy for diabetes and the implementation of a gluten-free diet for celiac disease.

Conclusions: Our case showed that the combination of autoimmune and autoinflammatory diseases, brought not only a challenging diagnostic process, but also complicated treatment.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent chronic liver diseases worldwide. The serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) has been recognized as a novel marker for metabolic diseases, including MASLD. However, all previous studies were performed in adults.

Objectives: To explore the relationship between the UHR and MASLD in Chinese children with obesity.

Methods: A retrospective study was conducted including 1284 obese children hospitalized at Beijing Children's Hospital between January 2016 and December 2022. Logistic regression analysis and restricted cubic splines were performed to assess the association between the UHR and the odds of MASLD. The receiver operator characteristic (ROC) curve analysis was used to estimate the diagnostic value of UHR for MASLD in children with obesity.

Results: The prevalence of MASLD was high, which reached 61.76% in children with obesity. UHR levels were higher in obese children with MASLD than those with non-MASLD for both genders. After dividing all individuals into three groups according to the tertiles of UHR, the prevalence rate of MASLD increased progressively from the tertile 1 to tertile 3 of UHR (34.11% vs. 70.56% vs. 80.61%). Logistic regression analysis showed that obese children with higher UHR levels were significantly associated with MASLD risk, independent of confounding factors such as age, gender, body mass index (BMI), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and creatinine (Cr). The non-linear relationship analysis demonstrated that a UHR between approximately 300 and 900 suggested a saturation effect of MASLD risk. ROC analysis indicated that UHR might serve as a predictive marker for diagnosing MASLD in obese children.

Conclusions: In children with obesity, UHR is significantly associated with MASLD and might serve as a novel and useful predictor for MASLD onset.

Background: Adrenal Vein Sampling (AVS) is the gold standard for categorizing primary aldosteronism (PA). However, catheterization of the right adrenal vein (RAV) can be technically challenging. This study aimed to investigate the validity of the right renal vertebral contour as fluoroscopic landmarks to help RAV orifice localization during AVS.

Methods: Imaging data of 310 PA patients were retrospectively analyzed. Patients were divided into Normal, Overweight, and Obese group based on their body mass index (BMI). A novel Renal-Vertebral-Angle (R-V-A) model was employed to delineate the distribution of the RAV orifice. This model concerned a cruciate cross formed by the upper edge of the right renal and the right edge of vertebral contour under fluoroscopy. The area within a 2 cm×2 cm square in the left upper quadrant of this cross was defined as the R-V-A. The success rate of AVS was compared across different BMI groups, as well as the differences in the distribution of the RAV orifice within the R-V-A.

Results: Successful RAV sampling was achieved in 270 cases, while the success rate of RAV sampling was found to be lower in the Obese group. The majority of the RAV orifices were located within the R-V-A region (249/270, 92.2%). There was no significant difference in the distribution of RAV orifices across the BMI groups (Normal vs. Overweight vs. Obese: 92.2% vs. 91.9% vs. 93.3%, p=0.968). In contrast to patients with successful RAV sampling, a significantly lower proportion of sampling site were found within the R-V-A in cases with mis-catheterized cases (92.2% vs. 55.6%, p<0.001).

Conclusion: The R-V-A model could be utilized as an anatomical landmark for the RAV orifice localization on fluoroscopy, that might help to narrow down the exploration range for RAV catheterization, and might offer beneficial assistance in enhancing the success rate for AVS.

Background: Diabetes and chronic obstructive pulmonary disease (COPD) are prominent global health challenges, each imposing significant burdens on affected individuals, healthcare systems, and society. However, the specific molecular mechanisms supporting their interrelationship have not been fully defined.

Methods: We identified the differentially expressed genes (DEGs) of COPD and diabetes from multi-center patient cohorts, respectively. Through cross-analysis, we identified the shared DEGs of COPD and diabetes, and investigated alterations of signaling pathways using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). By using weighted gene correlation network analysis (WGCNA), key gene modules for COPD and diabetes were identified, and various machine learning algorithms were employed to identify shared biomarkers. Using xCell, we investigated the relationship between shared biomarkers and immune infiltration in diabetes and COPD. Single-cell sequencing, clinical samples, and animal models were used to confirm the robustness of shared biomarkers.

Results: Cross-analysis identified 186 shared DEGs between diabetes and COPD patients. Functional enrichment results demonstrate that metabolic and immune-related pathways are common features altered in both diabetes and COPD patients. WGCNA identified 526 genes from key gene modules in COPD and diabetes. Multiple machine learning algorithms identified 4 shared biomarkers for COPD and diabetes, including CADPS, EDNRB, THBS4 and TMEM27. Finally, the 4 shared biomarkers were validated in single-cell sequencing data, clinical samples, and animal models, and their expression changes were consistent with the results of bioinformatic analysis.

Conclusions: Through comprehensive bioinformatics analysis, we revealed the potential connection between diabetes and COPD, providing a theoretical basis for exploring the common regulatory genes.

Purpose: This study aimed to investigate the alterations in diabetes risk associated with sarcopenia and insufficient physical activity, as well as the demographic shifts within the diabetic population.

Method: Utilizing pertinent data from the National Health and Nutrition Examination Survey (NHANES) database spanning 2011 to 2018, the criteria for sarcopenia were established by the Foundation for the National Institutes of Health. These criteria were calculated using lean body mass data in conjunction with body mass index data. Physical activity levels were assessed using the PAQ questionnaire from the NHANES database. The presence of diabetes was determined through the DIQ questionnaire and the laboratory examination within the NHANES database. The analysis was performed using multivariable logistic regression.

Result: The prevalence of both sarcopenia and insufficient physical activity in the diabetic population was 188% greater than in the non-diabetic population. Sarcopenia and insufficient physical activity were positively correlated with an increased risk of diabetes onset, demonstrating a 1.45-fold heightened risk when both conditions were present (OR=2.45,95%CI,1.35-4.44,P<0.05). This combined effect was significantly greater than the risk associated with sarcopenia alone (OR=1.84,95%CI,1.09-3.11,P<0.05) or insufficient physical activity alone (OR=1.55,95%CI,1.11-2.15,P<0.05).

Conclusion: A synergistic relationship exists between sarcopenia and insufficient physical activity, resulting in a markedly elevated risk of diabetes when both conditions are present concurrently. Therefore, comprehensive diabetes management strategies should prioritize populations exhibiting both sarcopenia and insufficient physical activity.

Diabetes insipidus (DI) is a rare endocrine disease involving antidiuretic hormone (ADH), encompassing both central and nephrogenic causes. Inability to respond to or produce ADH leads to inability of the kidneys to reabsorb water, resulting in hypotonic polyuria and, if lack of hydration, hypernatremia. DI cannot be cured and is an unfamiliar disease process to many clinicians. This diagnosis must be distinguished from primary polydipsia and other causes of hypotonic polyuria. The main branchpoints in pathophysiology depend on the level of ADH pathology: the brain or the kidneys. Prompt diagnosis and treatment are critical as DI can cause substantial morbidity and mortality. The gold standard for diagnosis is a water deprivation test followed by desmopressin administration. There is promising research regarding a new surrogate marker of ADH called copeptin, which may simplify and improve the accuracy in diagnosing DI in the future. Patients with DI require adequate access to water, and there are nuances on treatment approaches depending on whether a patient is diagnosed with central or nephrogenic DI. This article describes a stepwise approach to recognition, diagnosis, and treatment of DI.

[This corrects the article DOI: 10.3389/fendo.2024.1466245.].