International Journal of Endocrinology最新文献

Objective: Using network pharmacology and molecular docking technology to analyze the potential mechanism of the Jianpixiaoke recipe (JPXK recipe) in the treatment of type 2 diabetes mellitus (T2DM).

Method: This study searched and screened the active ingredients and corresponding T2DM-related targets of different herbs in JPXK recipe from multiple databases. Venn was used to screen the intersection targets of JPXK recipe targets and T2DM targets, and the intersection targets were imported into the STRING database to construct a PPI network. In addition, clustering and topology analysis were also used to analyze PPI networks. At the same time, a composite target network was constructed using Cytoscape software. Then, we further carried out GO and KEGG enrichment analysis on the targets and carried out molecular docking verification on key chemical ingredients and hub targets. Finally, the effect of this prescription on T2DM was verified through animal experiments.

Result: This study screened a total of 366 targets for the JPXK recipe, 1886 T2DM-related targets, and 214 intersecting targets. The active ingredients of the JPXK recipe were quercetin, isorhamnetin, luteolin, berberine, kaempferol, etc. Potential hub targets were ESR1, JUN, SRC, PIK3R1, FOS, MAPK1, AKT1, RELA, and MAPK3. The main pathways of the JPXK recipe in treating T2DM included the MAPK signaling pathway, cAMP signaling pathway, tumor necrosis factor signaling pathway, Toll-like receptor signaling pathway, etc. Molecular docking results showed that quercetin and luteolin combined best with the hub gene. JUN, FOS, AKT1, RELA, and MAPK3 interacted well with these critical ingredients. Animal experiments verified that the JPXK recipe had a good hypoglycemic effect.

Conclusion: This study revealed the active ingredients and potential molecular mechanism of the JPXK recipe in the treatment of T2DM, which provides valuable experience in future clinical trials.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and there are currently no biomarkers for DPN in clinical practice. The objective of this study was to explore the diagnostic value of urine for diseases and discover potential markers. Urinary proteomics was used to analyze urine samples from patients with DPN and healthy individuals. Quantitative analysis of mass spectrometry data was performed using both group-based and paired individual analysis strategies. A total of 2611 proteins were identified, of which 1759 were quantifiable, and 312 proteins showed significant differences (fold change > 2, adjusted p value < 0.01), with 239 decreased and 73 increased. A random grouping cross-validation strategy was employed to evaluate the differentially expressed proteins, ensuring that the probability of random differences was less than 10%. Unsupervised clustering analysis of urinary proteomes among groups could distinguish most specimens. The most enriched GO biological processes were cytoplasmic translation, translation, exocytosis, chaperone-mediated protein folding and immunoglobulin-mediated immune response. The most significant KEGG signaling pathways were ribosome, coronavirus disease (COVID-19), and metabolic pathways. Furthermore, some differentially expressed proteins were linked to the pathogenesis of diabetes, whereas others were associated with nerve damage. These molecules could serve as potential diagnostic and therapeutic biomarkers; some differential proteins have not yet been reported to be associated with DPN, providing clues for further research on their functions.

Background: Epidemiological studies suggest a potential link between diabetes mellitus (DM) and osteoarthritis (OA), but the molecular mechanisms underlying this association remain unclear. Identifying these mechanisms is crucial for developing targeted therapies for diabetic patients with OA.

Methods: A two-sample Mendelian randomization approach was used to assess causal relationships between DM and OA. Differential expression analysis of the GSE51588 and GSE21340 datasets identified common differentially expressed genes (co-DEGs), followed by GO and KEGG enrichment analysis. Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, and potential biomarkers were identified via CytoHubba and ROC curve analysis. Transcription factor (TF)-mRNA and mRNA-miRNA regulatory networks were developed to identify potential drug targets through DGIdb. Molecular docking and artificial intelligence (AI)-based ADMET analysis were performed to validate the interaction between GATA3 and PTEN. RT-qPCR was conducted to confirm the expression of PTEN and GATA3.

Results: Mendelian randomization identified a causal relationship between diabetes-related SNPs and OA. A total of 142 co-DEGs were identified, with PTEN and GATA3 showing significant diagnostic relevance. Molecular docking indicated that GATA3 inhibitors exhibited higher binding affinities than PTEN inhibitors, with ZK-806711 emerging as a promising dual-target inhibitor. ADMET analysis suggested that Genz-10850 is suitable for CNS-targeted therapy. In chondrocytes, hyperglycemia upregulated PTEN and downregulated GATA3 expression.

Conclusion: In conclusion, we identified the molecular mechanisms linking DM and OA, highlighting PTEN and GATA3 as potential therapeutic targets for intervention.

Background: This study aimed to investigate the relationship between serum osmolality and diabetic foot ulcers (DFUs).

Methods: We used data from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The association of each variable with DFU was explored. A multivariate logistic regression model was used to test the relationship between serum osmolality and DFU. In addition, we performed subgroup analyses to assess the reliability of the results.

Results: Serum osmolality was significantly associated with DFU (p value < 0.05). Multivariate logistic regression analysis showed a significant association between serum osmolality and DFU (OR = 1.04, 95% CI: 1.01-1.07). Participants in the higher osmolality group (281-312 mOsm/kg) had 2.14 times higher DFU prevalence than those in the lower group (245-280 mOsm/kg) (OR = 2.14, 95% CI: 1.29-3.55). In addition, subgroup analyses and cross-examinations confirmed that gender, age, and other variables did not significantly alter this association (all p values > 0.05).

Conclusions: We found that higher serum osmolality was associated with increased DFU odds. Close monitoring of serum osmolality levels in populations at high risk of DFU may facilitate early identification of the occurrence of DFU.

Prolactin (PRL) plays a variety of roles to maintain female reproductive functions. In female rats, Prl mRNA expression in the anterior pituitary was significantly suppressed by OVX. The OVX-induced inhibition of PRL expression was recovered by estradiol (E2) supplementation after OVX. Supplementation of progesterone (P4) and the androgen dihydrotestosterone (DHT) did not prevent the OVX-induced decrease of PRL expression. When E2 was administered to ovary-intact rats, Prl expression was significantly increased, but neither P4 nor DHT modulated its expression. In experiments using the PRL-producing GH3 cell line, a higher concentration of E2 significantly increased Prl expression; however, neither P4 nor DHT modulated its expression in these cells. Gene expression of thyrotropin-releasing hormone (TRH), a PRL-releasing factor within the hypothalamus, was unchanged by OVX. Similarly, OVX had no effect on the hypothalamic expression of the gene encoding tyrosine hydroxylase, a marker of dopamine that inhibits PRL. In addition, mRNA expression of TRH receptor and dopamine D2 receptor did not change by OVX within the pituitary. Moreover, the expression of follistatin (Fst) mRNA was increased following OVX and decreased with E2 supplementation in the anterior pituitary. However, FST had no effect on TRH-induced PRL synthesis. Our current observations suggest that the OVX-induced reduction of PRL principally depends on the depletion of E2. E2 has a direct effect on PRL-producing lactotrophs and increases PRL levels without affecting hypothalamic PRL-releasing/inhibiting factors.

Background: Thyroid cancer is the most common endocrine tumor, with its incidence increasing worldwide. Although differentiated thyroid cancer (DTC) generally has a good prognosis, some patients still experience recurrence or persistent lesions after initial treatment. This study aimed to explore the relationship between free thyroxine (FT4)/free triiodothyronine (FT3) ratio and short-term treatment response in patients with DTC.

Methods: A retrospective analysis was conducted on 225 patients with DTC who received treatment at the Nuclear Medicine Department of Deyang People's Hospital from 2019 to 2022. All patients underwent total or subtotal thyroidectomy followed by radioactive iodine therapy. Clinical data and preoperative laboratory test results were collected, and multivariable logistic regression analysis was used to evaluate the association between the FT4/FT3 ratio and the short-term treatment response in DTC, as well as trend analysis and restricted cubic spline (RCS) evaluation for nonlinear relationships.

Results: Among the 225 patients, 159 (70.7%) achieved an excellent response (ER). Compared to the non-ER group, the ER group had higher levels of FT4 (p = 0.040). After multivariate adjustment, the FT4/FT3 ratio was significantly associated with DTC prognosis (OR = 0.40, 95% CI: 0.22-0.68). Trend analysis showed that patients in the highest quartile of FT4/FT3 ratio were more likely to achieve ER status (OR = 0.20, 95% CI: 0.07-0.55; P for trend = 0.006). RCS analysis indicated a dose-response relationship between FT4/FT3 ratio and short-term prognosis of DTC (P for overall = 0.006; P for nonlinear = 0.887).

Conclusion: The FT4/FT3 ratio is significantly associated with short-term treatment response in patients with DTC. A higher FT4/FT3 ratio may be an independent predictive factor for a favorable prognosis in DTC patients. Future studies should further investigate its mechanisms and potential clinical applications.

Aim: We sought to evaluate the association of the Geriatric Nutritional Risk Index (GNRI), which assesses nutritional status, and sarcopenia among older individuals with type 2 diabetes mellitus.

Methods: We enrolled 292 type 2 diabetes mellitus patients aged 60 years and above in this cross-sectional study. This study took place at Şişli Hamidiye Etfal Training and Research Hospital (Istanbul, Turkey) between April 2024 and December 2024. European Working Group on Sarcopenia in Older People-2 (EWGSOP2) criteria were used to define sarcopenia. The relationship between sarcopenia and GNRI was investigated by logistic regression models.

Results: The average age was 72 years (range: 60-99). Of the 292 patients, 139 were male and 153 were female. Macrovascular complications and microvascular complications, such as neuropathy and nephropathy, were more common in sarcopenic patients. Low GNRI (< 98) was observed to be more in sarcopenic patients (p < 0.001). Multiple logistic regression analysis revealed an association between sarcopenia and neuropathy (p = 0.002) and macrovascular complications (p = 0.038).

Conclusions: Sarcopenia was more common in elderly type 2 diabetic patients with low GNRI. Our study emphasizes the high rate of malnutrition among sarcopenic patients, with a need for regular screening programs and the determination of elderly subjects requiring nutritional support. GNRI may serve as a screening indicator for the detection of malnutrition and sarcopenia in older diabetic individuals who are hospitalized.

Objective: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. This study investigated the potential causal association between Helicobacter pylori infection and DN.

Methods: The two-sample Mendelian randomization (MR) methodology and public data on DN and H. pylori infection from genome-wide association studies (GWASs) were used. The primary MR analytical method was the inverse variance weighted (IVW), complemented by additional methods such as MR-Egger, weighted median, and weighted mode. Results were validated through extensive sensitivity analyses, including tests for pleiotropy (PhenoScanner), directionality (bidirectional MR and Steiger test), and heterogeneity. A false discovery rate (FDR) was applied to correct for multiple testing.

Results: Among 7 H. pylori antibody markers, only genetically predicted catalase antibody levels showed a suggestive protective association with DN (odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.82-0.99, p = 0.03). However, this association did not withstand correction for multiple testing (P-FDR = 0.21). No significant causal effects were observed for other antibody markers. Sensitivity analyses found no evidence of horizontal pleiotropy and consistently supported a causal direction from H. pylori exposure to DN.

Conclusion: Our findings provide suggestive evidence for a potential causal link between the host immune response to H. pylori catalase and a lower risk of DN. This specific, biologically plausible pathway warrants further investigation in larger, more diverse populations to confirm its potential role in the pathogenesis of DN.

For patients with diabetes, achieving stable glucose control with minimal variability is highly significant. Incretin drugs have been shown to improve glycemic variability (GV), and we recently showed that a switch from a combination of a dipeptidyl peptidase (DPP)-4 inhibitor plus basal insulin to insulin degludec/liraglutide (IDegLira) improves GV, including the mean amplitude of glycemic excursions (MAGE), using continuous glucose monitoring in hospitalized patients with Type 2 diabetes. Here, we performed a secondary analysis to identify the factors related to an improvement in MAGE when switching to IDegLira. In patients with high MAGE, the change in C-peptide immunoreactivity during a glucagon test (ΔCPR) showed the highest correlation with the change in MAGE among the baseline patients' characteristics (ρ = -0.70; p < 0.05). Regression analysis confirmed a significant association between preserved CPR and amelioration of MAGE (R ² = 0.45; p < 0.05). Thus, this preliminary result implies that a treatment strategy that includes a glucagon-like peptide-1 receptor agonist might be beneficial for patients being treated with a DPP-4 inhibitor plus basal insulin who show high GV but have preserved beta-cell function.

Trial registration: University Hospital Medical Information Network (UMIN) Center Clinical Trials Registry: UMIN 000039460.

Background: Muscle weakness is associated with an increased risk of diabetes. However, its relationship with diabetic retinopathy (DR) in different genders remains unclear. This study aimed to investigate gender-specific associations between grip strength, lower limb function (assessed by the 30-s chair stand test, CST-30), and the prevalence of DR.

Methods: We conducted a cross-sectional analysis of 962 adults with diabetes aged 45 years or older. Participants underwent grip strength testing, a CST-30 assessment, and retinal examinations graded according to the Early Treatment DR Study (ETDRS) classification. Low grip strength was defined as less than 28 kg in men and less than 18 kg in women. Participants in the lowest two gender-specific quintiles of CST-30 scores were categorized as having reduced lower limb strength. Pearson correlation analysis was used to assess the relationship between grip strength and CST-30, and logistic regression analysis was employed to evaluate the associations with DR.

Results: Of the 962 participants with diabetes included, 404 were men. Grip strength was significantly but only modestly correlated with CST-30 in both men and women (r = 0.278 and 0.269, respectively). Further analysis revealed that, in men, low grip strength was independently associated with higher odds of DR (odds ratio [OR] = 2.98; 95% confidence interval [CI]: 1.33-6.68; p=0.008). However, reduced lower limb strength was not related to DR. In women, low grip strength was not associated with DR; however, reduced lower limb strength was significantly associated with DR (OR = 2.26; 95% CI: 1.18-4.34; p=0.014).

Conclusion: Our findings suggest that in middle-aged and older Chinese adults with diabetes, DR was related to grip strength in men but to lower limb strength in women, indicating a gender-specific difference.