International Journal of Endocrinology最新文献

Objective: Adult growth hormone deficiency (AGHD) is characterized by central adiposity and metabolic disorders. Asprosin, a newly discovered adipokine, plays a crucial role in connecting adipose tissue function with the development of metabolic syndrome. This study aims to evaluate the circulating levels of asprosin in AGHD patients and explore the potential correlation between asprosin levels and various metabolic parameters. Subjects and Methods: Forty male patients with AGHD (mean age: 33.5 ± 9.5 yrs and mean BMI: 25.0 ± 4.5 kg/m²) and forty age-, gender-, and BMI-matched non-AGHD controls were enrolled. Medical history, anthropometric parameters (weight, height, waist circumference), and biochemical and hormonal investigations were collected from the electronic medical record system. Fat mass, fat percentage, and fat-free mass (FFM) were evaluated by bioelectrical impedance. Serum levels of asprosin were measured by ELISA. Results: Patients with AGHD demonstrated notably increased waist-to-hip ratios, triglyceride levels, and decreased HDL-cholesterol levels compared with the control group. In additionally, AGHD patients exhibited significantly higher serum levels of asprosin compared with controls (p=0.039). A notable association was observed between serum asprosin levels and FFM, triglycerides, and HDL-cholesterol levels in the whole population. Conclusions: Our study highlights distinct metabolic alterations in AGHD patients when matched for BMI with controls and investigates variations in serum asprosin levels for the first time. These findings have significant implications for identifying potential biomarkers for metabolic syndrome risk in AGHD patients and informing future treatment approaches.

Objective: Mesenchymal stem cells (MSCs) have been highly confirmed for their critical role in the treatment of different diseases. This study focuses on the mechanism of umbilical cord-derived MSCs (UC-MSCs) in the treatment of ornidazole (ORN)-induced asthenozoospermia (AS) in rats via the AKT/mTOR pathway. Methods: An animal model of AS was established in ORN-induced rats, followed by treatment of UC-MSCs and rapamycin (autophagy activator) or MK-2206 (AKT inhibitor). The sperm motility, concentration, and viability of rats were measured by an automatic sperm analyzer. Hematoxylin and eosin (HE) staining was conducted to observe the pathological injury of testicular tissue in rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was utilized to evaluate the apoptosis rate of testicular cells. Western blot analysis was performed to determine the expression of apoptosis-related proteins, autophagy-related proteins, and AKT, p-AKT, mTOR, and p-mTOR. The rate of light chain 3 (LC3)-positive cells in testicular tissue was detected by immunohistochemistry (IHC). Results: In ORN-induced AS rats, sperm motility, concentration, and viability as well as the number of mesenchymal cells and spermatogenic cells were significantly decreased, spermatogenic tubule space, apoptosis rate, and cleaved caspase-3, LC3II/I, Beclin-1, and LC3-positive cell rates were increased, and Bcl2 was downregulated. UC-MSCs could improve sperm quality and testicular injury in AS rats by inhibiting excessive autophagy. Besides, UC-MSCs could activate the AKT/mTOR pathway. Moreover, inhibition of the AKT/mTOR pathway partially reversed the therapeutic effect of UC-MSCs on ORN-induced AS rats. Conclusion: UC-MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.

Objective: The utilization of radioactive iodine-131I (RAI) has long been established as a cost-effective and conventional treatment for managing Graves' disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD. Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2-h/6-h/24-h RAIU) prior to RAI treatment, the highest RAIU (RAIU_max), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established. Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p=0.005), thyroid volume (p=0.001), thyroid-stimulating hormone (TSH, p=0.042), ratio of RAIU at 6 h to 24 h (6-h/24-h RAIU, p=0.048), total 131I activity (p=0.026), and 131I activity per gram of thyroid tissue (p=0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692-0.846), indicating that the model has good discriminatory ability. Conclusion: Calculated-dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD.

Background: The prevalence of hyperuricemia is increasing globally. The health check-up population is a group of people dedicated to disease prevention in public health. This study aims to estimate the current prevalence of hyperuricemia among the health check-up population in economically developed areas of China using a healthcare database. Method: Healthcare data from 48,988 subjects in 12 provinces of China who had an annual health check-up in 2021 were used. Hyperuricemia was defined as a serum urate level > 420 mmol/L and/or a history of physician-diagnosed gout. An alternative definition of serum urate level > 420 mmol/L in men and > 360 mmol/L in women was used. The stratified prevalence of hyperuricemia by sex, age, region, and comorbidity group was reported. The association between hyperuricemia and sex, age, region, and comorbidities was analyzed in the multivariate logistic regression model. Results: In 2021, the sex- and age-adjusted prevalence of hyperuricemia was 13.6% in the total population (24.3% in men and 2.6% in women) based on the definition of serum urate level > 420 mmol/L. Regional prevalence varied considerably across the country, with the highest prevalence found in Fujian and the lowest in Liaoning Province (21.6% vs. 7.3%). Male sex, aging, hypertension, obesity, abdominal obesity, hypertriglyceridemia, and hypercholesterolemia were likely to be associated with hyperuricemia. Conclusions: This is the largest study using a healthcare database to indicate the prevalence of hyperuricemia in a health check-up population in an economically developed area of China. The current prevalence among the Chinese health check-up population was substantial, with a higher prevalence in males and in the eastern region. Hyperuricemia and its comorbidities warrant greater attention in the developed areas of China.

Background: Type 2 diabetes mellitus (T2DM) has emerged as a global epidemic issue, with high rates of disability and fatality. Traditional diagnostic biomarkers are typically detected once a metabolic imbalance has already occurred, thus the development of early diagnostic biomarkers is crucial for T2DM. Metabolomics studies have identified several predictive biomarkers for T2DM, including miR-320. Our previous research found that miR-320b was significantly downregulated in T2DM patients, but the underlying mechanism remains unclear. Therefore, this study was designed to investigate the significance of miR-320b for T2DM diagnosis and to explore the involved molecular mechanism. Methods: A total of 50 patients with T2DM and 80 sex- and age-matched healthy subjects were selected. The plasma miR-320b of all participations was detected by qRT-PCR and its correlations with other biomarkers of T2DM were analyzed. Besides, the expression of miR-320b in HepG2 cells was suppressed by miRNA inhibitors. Then the glucose consumption of HepG2 cells was measured. The target gene of miR-320b was predicted by four bioinformatics tools and intersected these prediction results by Venny method. The T2DM relevant target genes were identified by the GeneCards database. To ensure disease relevance, these T2DM relevant target genes were subsequently intersected with the target genes of miR-320b. Protein-protein analysis (PPI) was used to screening the gene with the most connections in these target genes. Finally, the target gene of miR-320b specific to T2DM was confirmed directly by luciferase reporter assay. The expression of target gene in HepG2 cell culture supernatant and plasma of all participations was detected. Results: Our results showed that the expression level of miR-320b was significantly lower in T2DM patients compared to the healthy controls. It was negatively correlated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment of insulin resistance (HOMA-IR), but positively with HOMA-β. The glucose consumption of HepG2 cells in the miR-320b inhibitor group was significantly lower compared to inhibitor-NC and blank control group. We predicted and confirmed that phosphatase and tensin homolog (PTEN) was the direct target gene of miR-320b using Bioinformation tools and luciferase reporter assay. Moreover, the concentration of PTEN was significantly higher in the HepG2 cell culture supernatant and plasma of T2DM patients. Conclusions: Our research demonstrated a negative correlation between miR-320b and FPG, HbA1C, and HOMA-IR, while exhibiting a positive correlation with HOMA-β. Suppressing miR-320b expression would impair glucose consumption of HepG2 cells through PI3K pathway by targeting PTEN. These results suggest that miR-320b may be a potential biomarker for diagnosing T2DM and a promising target for therapeutic intervention.

Metabolic syndrome (MetS) is a collection of metabolic abnormalities including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. Recently, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of metabolic balance, influencing the genes associated with MetS. Although the prevalence of insulin resistance is rising, leading to an increased risk of type 2 diabetes mellitus (T2DM) and its vascular complications, there is still a notable gap in understanding the role of lncRNAs in the context of clinical diabetes. Among lncRNAs, lung adenocarcinoma metastasis-associated transcript 1 (MALAT1) has been identified as a significant regulator of metabolism-related disorders, including T2DM and cardiovascular disease (CVD). This review explores the mechanism of lncRNA MALAT1 and suggests that targeting it could offer a promising strategy to combat MetS, thereby enhancing the prognosis of MetS.

Background: Fat mass and obesity-associated gene (FTO) genes rs9939609 is strongly associated with obesity and rs17817449 is an important and potential gene for obesity, have been well established. We aim to evaluate the relationship between FTO gene and overweight/obesity and confirm the influence of obesity on glucose and lipid metabolism parameters. Methods: We investigated 183 normal weight subjects and 193 individuals with overweight/obesity. Firstly, the effect of overweight/obesity on glucose and lipid metabolism parameters was analyzed. Then, the FTO genes rs9939609 and rs17817449 were counted to explore whether polymorphisms were associated with overweight/obesity and metabolic parameters. Results: Significant differences existed in glucose and lipid parameters between the group with overweight/obesity and control group. The rs9939609 and rs17817449 were strongly correlated with overweight/obesity. Haplotype analysis revealed that GA and GT haplotypes had 2.99 and 1.81 fold risk of overweight/obesity. FTO polymorphism also has effects on glucose and lipid metabolism parameters. Conclusions: There is a linkage imbalance between rs9939609 and rs17817449 in a Central China general population cohort, which also reflected the influence of FTO gene on the risk of overweight/obesity and total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) disorders. The new findings could provide new clues to predict obesity and metabolic diseases.

Objective: To determine the associations between triglyceride-glucose (TyG) index and mortality from all causes and cardiovascular causes in diabetic population. Methods: 3349 participants with diabetes mellitus (DM) from the 1999-2014 National Health and Nutrition Examination Surveys (NHANES), aged 18-85 years were included and grouped based on the TyG index in quintiles. Mortality was followed up through December 31^th, 2015. Cox proportional hazards models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs). We clarified the shape of association between TyG index and mortality using restricted cubic splines and piecewise linear regression. Results: After a median follow-up period of 82 months, 800 (23.9%) deaths occurred, of which 190 (5.7%) were due to cardiovascular causes. Participants in the top quintile had higher risks of all-cause mortality (HR, 1.38; 95% CI, 1.04-1.48) and cardiovascular mortality (HR, 2.43; 95% CI, 1.32-4.45) than those in the lowest quintile. TyG index and all-cause mortality had a J-shaped relationship with a threshold value of 9.32, while TyG index and cardiovascular mortality had a reversed L-shaped relationship with a threshold value of 9.37. Higher TyG index was associated with increased risks of all-cause mortality (per SD increment, HR, 1.52; 95% CI, 1.27-1.82) and cardiovascular mortality (per SD increment, HR, 2.17; 95% CI, 1.54-3.04) when above the threshold values. The sensitivity analyses demonstrated similar findings. Conclusions: TyG index in diabetic patients was nonlinearly correlated with mortality risks, potentially predicting all-cause and cardiovascular mortality.

Objective: Adropin is a unique hormone, which controls metabolism and energy homeostasis. Hyperthyroidism is a disease with a high metabolic rate that affects both glucose and lipid metabolism. We aimed to investigate the change of adropin levels and the association between adropin levels and clinical parameters in patients with hyperthyroidism. Methods: This cross-sectional study comprised 90 newly diagnosed patients with hyperthyroidism and 90 age- and gender-matched healthy controls. Circulating adropin levels and thyroid hormone levels were evaluated in each participant. Results: Compared with the healthy controls, the hyperthyroid patients had significantly higher levels of serum adropin (p < 0.001). In addition, adropin levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), whereas they were negatively correlated with thyroid-stimulating hormone (TSH). A multivariate linear regression analysis showed that serum adropin concentrations were independently correlated with FT3 and TSH after adjustment for age, gender, and other confounding factors (FT3: β = 0.231, p < 0.05; TSH: β = -0.301, p < 0.05). Conclusions: Patients with hyperthyroidism had elevated serum adropin levels. And the serum adropin concentrations were independently correlated with the FT3 and TSH levels.

Aims: Insulin resistance (IR) is an important risk factor for obesity and cardiometabolic diseases, and our previous findings have demonstrated that visceral fat area to skeletal muscle mass ratio (VSR) is significantly and positively associated with the risk of cardiometabolic diseases. Hence, this study aimed to investigate the relationship between VSR and multiorgan IR, provide a new approach to improve body composition, and set the basis for VSR to increase the incidence of cardiometabolic diseases. Materials and Methods: The study included 398 patients who underwent anthropometric and biochemical measurements, and body composition assessment. Spearman correlation analysis was used to investigate the correlation between VSR and homeostatic model assessment for insulin resistance (HOMA-IR) as well as multiorgan IR, including homeostasis model assessment adiponectin (HOMA-AD), adipose tissue insulin resistance (ADIPO-IR), and hepatic insulin sensitivity (HISI). The new model that incorporated into the present study is made up of easily measured biochemical indicators and is used to predict IR. Logistic regression was used to analyze the odds ratio (OR) of VSR on the risk of multiorgan IR. The predictive value of VSR for HOMA-IR and new model was evaluated using the receiver operating characteristic (ROC) curve. Results: VSR was significantly associated with HOMA-IR, HOMA-AD, ADIPO-IR, 1/HISI, and new model (p < 0.001). With the increase of VSR, the OR increased significantly for HOMA-IR and new model (p < 0.001). Then, multiorgan IR indicators were quantified, compared to the lowest quartile group, and increased VSR exacerbated the risk of IR in the highest quartile (p _trend < 0.001). The area under the curve for predicting IR using VSR for HOMA-IR and new model was 0.88 for men, 0.85 for women and 0.73 for men, 0.76 for women, respectively. Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR. Trial Registration: Clinical Trial Registry identifier: ChiCTR2100044305.