Frontiers in Endocrinology最新文献

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.].

Objective: To explore the differential gene expression in peripheral blood immune cells of individuals with type 2 diabetes mellitus (DM), comparing those with and without non-proliferative diabetic retinopathy (NPDR).

Methods: From a pool of 126 potential participants, 60 were selected for detailed analysis. This group included 12 healthy donors (HDs), 22 individuals with DM, and 26 with NPDR. We analyzed peripheral blood mononuclear cells (PBMCs) using RNA sequencing and quantitative PCR (qPCR) to pinpoint differentially expressed genes (DEGs). Western blot and flow cytometry were also employed to evaluate the protein expression of specific genes.

Results: In patients with NPDR compared to those with DM alone, MerTK-a gene implicated in inherited retinal dystrophies due to its mutations-was notably downregulated in PBMCs. Through flow cytometry, we assessed the protein levels and cellular distribution of MerTK, finding a predominant expression in monocytes and myeloid-derived suppressor cells (MDSCs), with a marked reduction in CD4+ and CD8+ T cells, as well as in natural killer T (NKT) cells. Patients with DM demonstrated a significant deviation in the PBMCs composition, particularly in B cells, CD4+ T cells, and NK cells, when compared to HDs.

Conclusions: The study indicates that MerTK expression in T cells within PBMCs could act as a viable blood biomarker for NPDR risk in patients with DM. Furthermore, the regulation of T cells by MerTK might represent a critical pathway through which DM evolves into NPDR.

Objective: Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis, as well as an independent risk factor of cardiovascular adverse events. We aimed to evaluate the association of serum Meteorin-like protein (Metrnl) level with carotid atherosclerosis as determined by carotid intima-media thickness (CIMT) status in subjects with T2DM.

Methods: This cross-sectional study included 83 T2DM subjects without pre-existing cardiovascular diseases. CIMT was measured by color doppler ultrasonography, while serum Metrnl level was measured by Enzyme-linked Immunosorbent Assay (ELISA) assay. According to the CIMT status, the subjects were divided into two groups: T2DM without atherosclerosis (DM-AS, CIMT<1.0mm) and T2DM with atherosclerosis (DM+AS, CIMT ≥1.0mm or carotid plaque).

Results: Serum Metrnl level was significantly increased in DM+AS group as compared to DM-AS group (0.77 ± 0.24 vs 0.51 ± 0.28 ng/ml, P <0.05). Binary logistic regression analysis showed that T2DM subjects in the fourth quartile of Metrnl levels demonstrated significantly higher risk of the presence of carotid atherosclerosis (P <0.05). The ROC curve used to identify the diagnostic accuracy of serum Metrnl level in the predication of T2DM subjects with carotid atherosclerosis revealed an area under the curve (AUC) of 0.742. The optimal cut-off value was 0.61 ng/ml with a sensitivity of 77.6% and a specificity of 58.8%.

Conclusions: This cross-sectional study clearly demonstrated that elevated serum Metrnl level was significantly associated with higher risk of the presence of carotid atherosclerosis. Metrnl is a promising therapeutic target for T2DM and its macro-vascular diseases.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.

[This corrects the article DOI: 10.3389/fendo.2024.1392418.].

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which has poor prognosis with a short median overall survival of 6-12 months and a low 5-year survival rate of approximately 3%. It is crucial to remove PanIN lesions to prevent the development of invasive PDAC, as PDAC spreads rapidly outside the pancreas. This review aims to provide the latest knowledge on PanIN risk, pathology, cellular origin, genetic susceptibility, and diagnosis, while identifying research gaps that require further investigation in this understudied area of precancerous lesions. PanINs are classified into PanIN 1, PanIN 2, and PanIN 3, with PanIN 3 having the highest likelihood of developing into invasive PDAC. Differentiating between PanIN 2 and PanIN 3 is clinically significant. Genetic alterations found in PDAC are also present in PanIN and increase with the grade of PanIN. Imaging methods alone are insufficient for distinguishing PanIN, necessitating the use of genetic and molecular tests for identification. In addition, metabolomics technologies and miRNAs are playing an increasingly important role in the field of cancer diagnosis, offering more possibilities for efficient identification of PanIN. Although detecting and stratifying the risk of PanIN poses challenges, the combined utilization of imaging, genetics, and metabolomics holds promise for improving patient survival in this field.