International Journal of Endocrinology最新文献

Objective: This study aimed to evaluate whether the ten-individual plasma-level of free fatty acids (FFAs) affect the risk of nonalcoholic fatty liver disease (NAFLD) which is featured by triglycerides (TGs) deposition because the observational studies are limited and conflicting about the causal effect between FFAs and NAFLD.

Design and methods: This analysis was a large genome-wide association study (GWAS) summary statistic. Fourteen independent single-nucleotide polymorphisms (SNPs) without linkage disequilibrium (r ² < 0.005) that were strongly associated (p < 5 × 10^-8) with FFAs were chosen as instrumental variables to estimate the causal effect of genetic variants on the levels of 10 phospholipid FAs through GWAS, and summary estimates were obtained using the inverse-variance weighted (IVW) method applied to SNPs. And the summary-level data of European participants from the eMERGE network, the FinnGen cohorts, the UK Biobank, and the Estonian Biobank, for the latest and largest GWAS datasets for NAFLD (8434 cases and 770,180 controls), were obtained. Mendelian randomization analysis was applied.

Results: The result demonstrated that 10 individual FFAs were not significantly associated with NAFLD.

Conclusion: The evidence to support the causal association of the individual plasma FFAs with NAFLD is insufficient in this study.

Background: Diabetic retinopathy (DR), a microvascular disease, also involves retinal neurodegeneration. Müller cells exert an important role in the retina, and their destabilization and reduction affect the physiological function of the retina. To investigate the effect and mechanism of hedgehog acyltransferase-like (Hhatl) on Müller cells in DR.

Methods: The differentially expressed genes (DEGs) in Müller cells of DR rats were first analyzed by single-cell transcriptomics techniques (scRNA-seq). Regulating Hhatl expression, cell viability was detected using cell counting kit-8 (CCK-8) assay; apoptosis was detected by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL); the expression of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) was assessed by immunofluorescence; and Ca²⁺ concentration was determined by fluorescence quantification to observe the effect and mechanism of Hhatl on Müller cells of the high glucose (HG)-treated rats. Finally, the results of the cell assays were verified in male 6-week-old Zucker (fa/fa) diabetic fatty (ZDF) rats. Viral vectors expressing Hhatl were injected into the vitreous of ZDF rats, and apoptosis and endoplasmic reticulum stress (ERS)-related indices in rat retinal cells were detected using immunofluorescence.

Results: scRNA-seq analysis revealed that Hhatl was low-expressed in Müller cells of DR rats. In vitro assays confirmed that upregulation of Hhatl could increase rMC-1 Bcl2 expression, decrease Bax expression, and reduce apoptosis in HG environments. In addition, Hhatl did downregulate ATF6 expression, decrease CHOP and GRP78 levels, and reduce Ca²⁺ concentration. Animal assays showed that Hhatl overexpression in the vitreous of ZDF rats did elevate Bcl2 level, decrease Bax expression, and reduce ATF6, CHOP, and GRP78 levels, which alleviated ERS in the retina of ZDF rats.

Conclusion: Hhatl reduces apoptosis of Müller cells in DR by alleviating ATF6-related ERS signaling.

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a groundbreaking treatment for Type 2 diabetes mellitus (T2DM) and obesity. Initially developed for glycemic control, recent clinical and preclinical data reveal its broader therapeutic potential across a range of metabolic and systemic conditions. This review explores tirzepatide's mechanisms of action, clinical efficacy, and safety profile, with particular attention to its impact on T2DM, obesity, cardiovascular health, metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD), and neurological disorders such as Alzheimer's and Parkinson's diseases. By addressing multiple pathophysiological pathways, including insulin resistance, inflammation, and oxidative stress, Tirzepatide presents a unique opportunity to redefine treatment paradigms beyond glycemic management. Our review also synthesizes recent evidence on the efficacy and safety of tirzepatide for obesity management specifically in Asian populations; a group frequently underrepresented in global trials. This demographic focus introduces a valuable dimension to the existing body of knowledge. As ongoing trials continue to evaluate its long-term effects, tirzepatide stands at the forefront of a new era in integrated cardiometabolic and neuroprotective therapeutics.

Background and Objective: Danggui Liuhuang decoction (DLD) demonstrates pharmacological efficacy in the treatment of hyperthyroid kidney disease (HKD). However, the underlying therapeutic mechanism remains inadequately understood. This study aims to elucidate the therapeutic mechanism of DLD in HKD rats by integrating the determination of effective component content, network pharmacology, in vivo verification, and metabolomics, with a focus on the alterations in metabolites and metabolic pathways. Methods: The concentrations of 12 components, including berberine, in DLD were quantified using high-performance liquid chromatography. Network pharmacology was utilized to investigate the interactions between drug targets and disease targets and to predict functional pathways. A rat model of HKD was established to verify the therapeutic mechanism of DLD, which was further elucidated through metabolomics analysis. Results: The quantification of 12 components, including berberine, in DLD was successfully achieved. Key targets such as TNF and AKT1, along with the PI3K/AKT and MAPK signaling pathways, were identified as critical pathways through network pharmacology analysis. Animal experiments robustly demonstrated the therapeutic efficacy of DLD on HKD, corroborating the network pharmacology findings via histopathological analysis, ELISA, and Western blot (WB). Metabolomics studies revealed significant alterations in 49 metabolites pre- and posttreatment, with notable changes in linoleic acid metabolism and arachidonic acid metabolism pathways. Linoleic acid, arachidonic acid, and 5-HETE were identified as potential biomarkers. Conclusion: The therapeutic efficacy of DLD in HKD rats was substantiated, and the underlying mechanisms were preliminarily elucidated, thereby providing a foundation for further investigation into the pharmacodynamic substances and mechanisms of action.

Objectives: This multicenter cross-country study aimed to assess and compare the short- and long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in distinct national treatment settings. Materials and Methods: This retrospective study analyzed low-risk PTMC patients who received US-guided RFA at 6 medical centers in 2 countries (Taiwan and Vietnam) between November 2017 and April 2023. US and computed tomography (CT) were performed to assess and compare the PTMC tumors, changes in tumor size, and disease progression. Repeated measure ANOVA and two-way mixed ANOVA were used to analyze within-group and between-group differences among volume and volume reduction ratio (VRR). Student's t-test and the standard chi-square test were used to compare between-group data, while paired t-test was used to compare within-group data. Results: A total of 206 patients (mean age: 44.8 ± 12.5 years [range, 19-87], 44 men) with 224 PTMC tumors were enrolled and treated. Four (1.9%) patients reported transient hoarseness as complications. All tumors exhibited a reduction in size (p < 0.001) at 12 month post-RFA, while 58.5% (131/224) of PTMCs had completely disappeared under US examination at the last follow-up. One patient had developed ipsilateral cervical LN metastasis at the 6-month follow-up. While the VRR showed a statistical difference between the two countries in the short term (p < 0.001), this difference was not observed at 2 year follow-up (p=0.159). Conclusions: US-guided RFA is an effective and safe procedure for patients with PTMC. Furthermore, we noted no long-term differences in terms of procedural outcomes under the distinct national treatment settings.

Background: Osteoporosis represents a critical public health challenge, particularly among postmenopausal women, characterized by reduced bone mineral density (BMD) and increased fracture risk. Traditional obesity metrics such as body mass index (BMI) and waist circumference (WC) have limitations in assessing bone health due to their inability to differentiate lean and fat mass. The weight-adjusted waist index (WWI), a novel anthropometric indicator, offers a more nuanced approach to evaluating body composition and metabolic risks. Objective: The WWI is a novel obesity metric that demonstrates superior accuracy in evaluating both muscle mass and adiposity compared to conventional anthropometric measurements. This cross-sectional study examined the relationship between WWI and BMD at the femoral neck in a nationally representative sample of American postmenopausal women. Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES), including 3198 postmenopausal women aged 40 and older. WWI was calculated by dividing WC by the square root of body weight. BMD was assessed using dual-energy X-ray absorptiometry (DXA). Multivariate regression analyses were performed, adjusting for potential confounders including age, race, height, BMI, and metabolic markers. Results: Multiple regression analyses revealed a significant negative correlation between WWI and femoral neck BMD. A critical threshold of 10.32 was identified, beyond which the relationship with BMD shifted. Below this threshold, higher WWI levels showed a protective effect on BMD (β = 0.03, p=0.0265), while above the threshold, WWI exhibited a significant negative influence (β = -0.01, p < 0.0001). Stratified analyses demonstrated variations in the WWI-BMD relationship across different subgroups, including age, race, and menopause status. Conclusion: This cross-sectional analysis revealed a significant negative correlation between the WWI and femoral neck BMD in a nationally representative cohort of American postmenopausal women. Notably, the association demonstrated a nonlinear inverted U-shaped pattern with an identifiable threshold effect.

Background: Atypical femoral fractures (AFFs) are rare but serious complications of antiresorptive therapy (ART), frequently misdiagnosed and managed inappropriately in acute care settings. Early recognition remains critical to avoid further harm. Objective: To compare the clinical and biochemical characteristics of patients with AFFs and typical femoral fractures (TFFs) to identify features that may assist in diagnosis at the time of hospitalization. Methods: A retrospective study was conducted across two tertiary hospitals in Queensland, Australia, from 2012 to 2022. Patients presenting with femoral shaft fractures were identified using ICD-10 codes. Fractures were classified radiologically using ASBMR criteria. Clinical characteristics, biochemical results, and discharge medications were extracted from electronic records. Between-group comparisons were performed using appropriate statistical tests. Results: Of 869 identified fractures, 43 AFFs and 101 TFFs were confirmed. Patients with AFFs were more likely to have a prior diagnosis of osteoporosis (97.7% vs. 35.6%, p < 0.01), a history of fragility fracture (53.5% vs. 26.7%, p < 0.01), and prodromal symptoms (32.6% vs. 3%, p < 0.01). Biochemically, AFF patients had significantly lower alkaline phosphatase (median 56 vs. 83 IU/L, p < 0.01) and higher 25-hydroxyvitamin D levels (median 86.8 vs. 69.5 nmol/L, p=0.01). Nearly one-quarter had ALP < 40 IU/L. Despite this, 51.3% of AFF patients were discharged on continued ART. Conclusions: Patients with AFFs demonstrate distinct clinical and biochemical profiles at the time of hospital presentation, most notably suppressed ALP. These features may serve as diagnostic clues to prevent ongoing exposure to ART. Greater clinical vigilance is needed to ensure appropriate management and to consider alternative diagnoses such as hypophosphatasia in selected patients.

Aim: This study aimed to analyze the relationship between sensitivity to thyroid hormones and insulin resistance (IR) in people with different levels of body mass index (BMI). Methods: We included 32,478 euthyroid participants, and they were divided into three groups according to body mass index (BMI): normal weight (n = 20,200), overweight (n = 10,178), and obesity (n = 2100). We used the Thyroid Feedback Quantile-based Index (TFQI), the TSH index (TSHI), and the Thyrotroph T4 Resistance Index (TT4RI) to represent thyroid hormones sensitivity and used Triglyceride-Glucose (TyG) Index, the Atherogenic Index of Plasma (AIP), and The Metabolic Score for Insulin Resistance (METS-IR) to represent IR. Results: In the BMI < 25 kg/m² group, linear regression showed that TFQI, TSHI, and TT4RI were all positively correlated with TyG (β = 0.096, 0.089, and 0.089, respectively, all p < 0.001). Logistic regression showed that the odds ratios (ORs) for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.430, 1.537, and 1.518, respectively (all p < 0.001), compared with the lowest quartiles of the TFQI, TSHI, and TT4RI. In the 25 ≤ BMI < 29.9 kg/m² group, TFQI, TSHI, and TT4RI were positively associated with TyG (β = 0.071, 0.067, and 0.066, respectively, all p < 0.001) according to linear regression. The ORs for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.269, 1.363, and 1.353, respectively (all p < 0.001) by logistic regression. In the BMI ≥ 30 kg/m² group, positive correlations were found between the three thyroid indices and TyG (β _TFQI = 0.097, β _TSHI = 0.084, β _TT4RI = 0.083, all p < 0.01) by linear regression. The ORs for having high TyG in the highest quartiles of the TFQI, TSHI, and TT4RI were 1.298 (p=0.101), 1.454 (p=0.05), and 1.455 (p=0.05), respectively. Conclusions: Reduced sensitivity to thyroid hormones was associated with high levels of IR in euthyroid adults of normal weight and overweight. In obese patients, no significant correlation was found between sensitivity to thyroid hormones and IR.

Purpose: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of this study is to identify noninvasive biomarkers for early-stage DKD or targets for DKD treatment through the analysis of urinary exosomal miRNA expression profiles in DKD patients. Methods: The urinary exosomes were isolated from type 2 diabetes (T2DM) patients with DKD confirmed by renal biopsy (DKD-Exo). The urinary exosomal miRNAs expression profiles were detected using miRNA sequencing, and differentially expressed miRNAs were verified by real-time quantitative PCR. Target genes of these miRNAs and relevant pathways in DKD were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Human podocytes and renal tubular epithelial cells (TECs) were treated with DKD-Exo to investigate the effects of DKD-Exo on podocyte apoptosis and the epithelial-mesenchymal transition (EMT) of TECs. Results: A total of 40 miRNAs were found to be differentially downregulated, 17 of which were named and 23 were untitled; miR-371a-3p, miR-371a-5p, miR-1260b, miR-222-3p, miR-1224-5p, and miR-1253 were reported in DKD for the first time. GO and KEGG pathway analyses suggest that these target genes are related to cellular apoptosis and renal fibrosis in DKD, and are involved in 135 pathways. In vitro, DKD-Exo induced the apoptosis of podocytes and collagen synthesis in TECs. Conclusion: Our study implies that the urinary DKD-Exo could deliver biological information to podocytes or TECs, which play an important role in pathogenesis of DKD.

Background/Objective: Thyroid hormones are central to the regulation of energy expenditure and homoeostasis. An important microelement required for the optimal function of the thyroid gland is selenium. The question of whether Nigerian patients with thyroid disorders are deficient in selenium is what this study aims to answer. Methods: This was a comparative cross-sectional study carried out at a tertiary hospital in Southwest Nigeria. Fifty individuals with various thyroid disorders who gave consent were consecutively recruited and compared with one hundred apparently healthy age and sex-matched controls. Blood samples were collected for free thyroxine, free triiodothyronine, thyroid-stimulating hormone and selenium levels. The thyroid hormones were assayed with enzyme-linked immunoassay. Selenium was measured using inductively coupled plasma optical emission spectroscopy. Data were analysed with SPSS Version 26. Results: The mean age of the subjects and control was 40.3 ± 10.6 and 38.0 ± 9.1 years, respectively (p=0.157). The subjects and controls were predominantly females, 80% and 72%, respectively. Thyroid disorders were most prevalent in the 41-50 years age category. The male:female ratio was 1:4. The majority of the cases (60%) had biochemical evidence of hyperthyroidism, 28% were euthyroid and 12% were hypothyroid. Selenium levels were significantly lower among the cases than healthy controls (mean selenium level: 24.9 ± 15.7 and 59.0 ± 35.9 μg/L, respectively, p < 0.001). With normal selenium levels of 80 μg/L, all the participants were deficient in selenium. There was no significant difference in selenium levels across the spectrum of thyroid disorders although the mean selenium levels were lowest for the hypothyroid subjects. Conclusion: There is significant selenium deficiency in all subjects with thyroid disorders; apparently, healthy Nigerians are generally deficient. Selenium supplementation is recommended for Nigerian patients with thyroid disease and may be required for the general population.