Frontiers in Endocrinology最新文献

Background: Insulin resistance (IR) contributes substantially to the development of cardiovascular disease (CVD) and metabolic disorders, particularly obesity. The homeostatic model assessment of IR is a prevalent IR indicator, but insulin measurement is quite impractical for widely use. Given its convenience and accessibility, the triglyceride-glucose (TyG) index, along with modified indices such as the triglyceride-glucose-waist circumference (TyG-WC) and triglyceride-glucose-waist-height ratio (TyG-WHtR), are gaining recognition as practical tools for assessing IR. This study aimed to investigate the specific correlation between the TyG index and its modified indices with arterial stiffness in an overweight or obese population and to explore novel, self-defined modified TyG indices for identifying individuals at elevated risk for such conditions.

Methods: This retrospective study included 1,143 overweight or obese individuals from 2021 to 2023. Medical data, including brachial-ankle pulse wave velocity (baPWV), were collected. Two novel modified TyG indices, TyG-1h and TyG-2h, were defined by substituting the fasting glucose level in the TyG formula with 1-hour and 2-hour post-load plasma glucose levels, respectively. Multivariate logistic regression analyses were conducted to identify parameters that demonstrated a statistically significant correlation with arterial stiffness, defined as a baPWV threshold of ≥ 1400 cm/s. Additionally, restricted cubic spline (RCS) modelling was employed to further explore these relationships in a visually interpretable manner. To evaluate and compare the diagnostic accuracy of the conventional TyG index and its novel modified versions, receiver operating characteristic (ROC) curve analyses were performed.

Results: Our findings revealed that individuals with arterial stiffness presented significantly elevated TyG index and all its modified versions (P< 0.05). By utilizing a binary logistic regression model and adjusting for potential confounders, we determined that all TyG-related parameters independently correlated with an increased risk of developing arterial stiffness. Moreover, TyG-WHtR displayed the best correlation (OR 3.071, 95% CI 1.496-6.303) when stratified by quartiles, followed by TyG-1h (OR 2.298, 95% CI 1.248-4.234) and TyG-2h (OR 2.115, 95% CI 1.175-3.807). ROC curves suggested that TyG-1h and TyG-2h demonstrated superior diagnostic performance compared to TyG, with AUCs of 0.685, 0.679 and 0.673, respectively.

Conclusions: The modified TyG indices exhibited strong effectiveness in identifying arterial stiffness in Chinese overweight or obese individuals.

Background: Erectile dysfunction (ED) is considered the tip of the iceberg for cardiovascular disease (CVD). However, there is still conflicting evidence regarding their relationship. Recently, a validated tool for the Atherosclerotic Cardiovascular Disease (ASCVD) risk score has provided a key opportunity to delve deeper into the relationship between ED and CVD. Therefore, we intended to assess the relationship between ED and 10-year ASCVD risk score.

Methods: Complete data of 1207 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) were used in the study. Various weighted logistic and linear regression models were employed to investigate the effect of the presence of ED on the higher 10-Year ASCVD risk score or high risk of 10-Year ASCVD. Conversely, logistic regression models were repeated to explore the effect of continuous or categorical ASCVD risk score on the prevalence of ED. Sensitivity analyses were also conducted, focusing on severe ED with a more stringent definition. Additionally, we supplemented our study with subgroup analyses, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) analysis to enhance the robustness of our results.

Results: Participants with ED had higher ASCVD risk scores and a higher risk of ASCVD, which corresponded to a greater prevalence of ED or severe ED. When considering the presence of ED as the exposure, our results indicated that the presence of ED increased the ASCVD risk score (Model 3: β [95%CI]: 2.09 [1.12, 3.06]) in Model 3, as well as the high risk of ASCVD (OR [95%CI]: 2.27 [1.13, 4.59]). Conversely, a continuous increase in the ASCVD risk score was also associated with an increased prevalence of ED (OR [95%CI]: 1.04 [1.02,1.06]). Additionally, those in the borderline ASCVD risk group (OR [95% CI]: 2.95 [1.60, 5.44]), intermediate ASCVD risk group (OR [95% CI]: 4.53 [2.35, 8.73]), and high ASCVD risk group (OR [95% CI]: 7.62 [3.19, 18.19]) exhibited progressively increasing ED risk when compared to the low-risk group. Furthermore, the RCS analysis demonstrated a linear relationship between ED prevalence and the continuous ASCVD risk score, with the latter showing high efficacy in predicting ED (AUC [95%CI]: 0.794 [0.768, 0.821]).

Conclusions: The presence of ED may precede the onset of ASCVD by some years. Consequently, timely and dynamic evaluation of the cardiovascular status provides an earlier opportunity to identify and implement effective prevention strategies to promote cardiovascular health for ED patients.

Introduction: Congenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.

Methods: Forty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023. Genetic testing (n=40), 18F-fluorodihydroxyphenylalanin and 68Ga-DOTANOC PET/CT imaging followed by surgical treatment and subsequent histological analysis (n=19) was performed through international collaboration.

Results: Pathogenic variants were identified in 19/22 (86.3%) individuals with persistent CHI (p-CHI) and 8/18 (44.4%) with early remission CHI (er-CHI). Pathogenic variants in the K-ATP channel genes were the only identified genetic cause of p-CHI (ABCC8 (n=17) and KCNJ11 (n=2)) with greater genetic heterogeneity observed in those with er-CHI (ABCC8 (n=3), KMT2D (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and INSR (Donohue syndrome (n=2)). Histological analysis performed on 19 children with persistent CHI confirmed focal disease in 14 (73.7%), diffuse disease in two (10.5%) and atypical histology in three (15.8%). After surgery, complete recovery was observed in all 14 with focal disease, while relapse occurred in three patients with diffuse or atypical histology.

Conclusion: A genetic diagnosis was achieved for 67.5% (27/40) of the cohort with a higher pick-up rate observed in those with p-CHI. The genetics and imaging studies enabled subtype-targeted treatment with surgical cure achieved in all individuals with focal disease.

Objective: Current research suggests that irisin is closely linked to the pathogenesis and progression of metabolic dysfunction-associated fatty liver disease (MAFLD). This systematic review and meta-analysis updates our previous meta-analysis and further explores the relevance between circulating irisin levels and MAFLD.

Methods: Nine databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, Weipu, CBM, Clinicaltrials.gov and gray literature) were retrieved as of 1^st August, 2024. The standardized mean difference (SMD) and 95% confidence interval (CI) represent pooled effect size. We used the Newcastle-Ottawa Scale to evaluate the quality of articles and the certainty of evidence assessed by GRADE system. All statistical analyses were performed using RevMan 5.3 and Stata 12(Stata Corporation, yi TX).

Results: Fifteen case-control studies were included. Circulating irisin levels in the MAFLD group were markedly lower than those in the healthy group (SMD=-1.04 [-1.93, -0.14]). Subgroup analyses by race, age, severity and T2DM revealed that circulating irisin levels were lower in the MAFLD group compared to those in the healthy controls in the Asian population (SMD=-1.38 [-2.44, -0.31], P<0.05) and in those above 50 years old (SMD=-2.23 [-3.64, -0.81], P<0.05) and higher in the mild MAFLD groups than those in moderate to severe MAFLD groups (SMD = 11.68 [9.05, 14.31], P<0.05). And the circulating irisin levels in MAFLD patients with T2DM were significantly lower than those in healthy group (SMD = -2.90 [-4.49, -1.30]). ELISA kits from different companies also presented different relationships.

Conclusions: There were significantly lower circulating irisin levels in the MAFLD group than in the healthy control group. Although these results differed from our previous results, there is no denying that circulating irisin levels are closely associated with the advancement of MAFLD.

Background: Glucocorticoid-induced adrenal insufficiency (GIAI) is a hypothalamic-pituitary-adrenal (HPA) axis dysfunction caused by long-term use of exogenous steroids. Adrenal crisis (AC) is an acute complication of GIAI and one of the reasons for the increased risk of death. This study aims to analyze the clinical characteristics of GIAI patients with AC and explore the related risk factors.

Methods: Clinical data of adult GIAI patients treated at our hospital between January 1, 2014, and December 31, 2023 were included. The demographic characteristics, clinical characteristics, laboratory tests and comorbidities of the patients were collected. Univariate and multivariate regression analyses were used to explore the variables related to the occurrence of AC, and prediction models were constructed.

Results: 51 patients (13.75%) developed AC during hospitalization. Mortality was significantly higher in patients with AC than in those without AC. Multivariate logistic regression analysis showed that infection, psychiatric symptoms, serum sodium, albumin, neutrophil-lymphocyte ratio (NLR) and eosinophil-lymphocyte ratio (ELR) were independent risk factors for AC. Among the prediction models constructed by machine learning algorithms, logistic regression model had the best prediction effect.

Conclusion: This study investigated the clinical characteristics of AC in GIAI patients. NLR and ELR may be effective predictors of AC in GIAI patients, and combined with other clinically significant indicators, an effective prediction model was constructed. Logistic regression model had the best performance in predicting AC in GIAI patients.

Introduction: Acromegaly is a disease characterized by enhanced bone turnover with persistently high vertebral fracture risk. Sclerostin is a glycoprotein, which acts as an inhibitor of bone formation and activates osteoclast-mediated bone resorption. The osteoprotegerin (OPG)/receptor activator for the nuclear factor κ B ligand (RANK-L) system is crucial for controlling bone metabolism.

Objective: The study aimed primarily at evaluating sclerostin, OPG, and RANK-L concentrations in patients at different stages of acromegaly activity. The secondary aim was to identify an association of sclerostin with the OPG/RANK-L system and bone mineral density (BMD).

Materials and methods: The study enrolled 126 patients aged 40 to 80 years, including 72 patients with acromegaly and 54 controls (CG). The acromegaly patients were further classified into the following subgroups: active acromegaly (AA), controlled acromegaly (CTA), and cured acromegaly (CA). Blood samples were taken from the participants to measure sclerostin, OPG, RANK-L, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Dual-energy X-ray absorptiometry was performed at the lumbar spine and hip.

Results: Significantly lower sclerostin concentrations were observed in acromegaly patients compared with CG (AA, CTA, CA, CTA+CA, AA+CTA+CA vs CG; p < 0.001). Significant differences in OPG concentrations were revealed between the following groups: CTA vs CA (p=0.002), CTA vs CG (p<0.001), CTA+CA vs. CG (p<0.001), and AA+CTA+CA vs. CG (p<0.001). There were no significant differences in RANK-L concentrations between studied groups, regardless of the adopted classification (p>0.05). There were no statistically significant correlations between sclerostin and GH/IGF-1 or BMD. In the AA+CTA+CA group, there was a statistically significant positive correlation between SCL and OPG concentrations (r=0.271; p=0.022). A significant negative correlation between SCL and RANK-L was found in the AA group (r=-0.738; p=0.046).

Conclusions: Patients with acromegaly have lower sclerostin concentrations than healthy controls, which may be a result of a compensatory mechanism to increased bone loss. The influence of the GH/IGF-I axis on bone remodeling may be mediated in part by the OPG/RANK-L system. The interaction between SCL and OPG/RANK-L system in acromegaly should be further elucidated.

Aims: This study investigates the role of Hepatocyte Nuclear Factor 4α (HNF4α) in the adaptation of pancreatic β-cells to an HFD-induced obesogenic environment, focusing on β cell mass expansion and metabolic adaptations.

Main methods: We utilized an HNF4α knockout (KO) mouse model, with CRE-recombinase enzyme activation confirmed through tamoxifen administration. KO and Control (CTL) mice were fed an HFD for 20 weeks. We monitored body weight, food intake, glucose tolerance, insulin sensitivity, and insulinemia. Also, to assess structural and metabolic changes, histological analyses of pancreatic islets and liver tissue were conducted.

Key findings: KO mice displayed lower fasting blood glucose levels compared to CTL mice after tamoxifen administration, indicating impaired glucose-regulated insulin secretion. HFD-fed KO mice consumed less food but exhibited greater weight gain and perigonadal fat accumulation, reflecting higher energy efficiency. Histological analysis revealed more pronounced liver steatosis and fibrosis in KO mice on HFD. Glucose intolerance and insulin resistance were exacerbated in KO mice, highlighting their inability to adapt to increased metabolic demand. Structural analysis showed that KO mice failed to exhibit HFD-induced β cell mass expansion, resulting in reduced islet diameter and number, confirming the critical role of HNF4α in β cell adaptation.

Significance: This study demonstrates that HNF4α is essential for the proper metabolic and structural adaptation of pancreatic β-cells in response to an obesogenic environment. The lack of HNF4α impairs β cell functionality, leading to increased susceptibility to glucose intolerance and insulin resistance. These findings underscore the importance of HNF4α in maintaining glucose homeostasis and highlight its potential as a therapeutic target for diabetes management in obesity.

Background: Oxidative stress has an important role in type 2 diabetes (T2D). Oxidative balance score (OBS) is an emerging assessment of dietary and lifestyle oxidative balance. We aimed to explore the association of OBS with cardiovascular disease (CVD) and all-cause and CVD mortality in the T2D population through NHANES 1999-2018.

Methods: OBS integrated 16 dietary components and 4 lifestyle components. T2D was diagnosed according to the American Diabetes Association criteria. Multivariate logistic regression and multivariate Cox proportional hazards regression analyses were used to explore the association of OBS with CVD and mortality in T2D, respectively.

Results: 3801 adult T2D participants were included. In fully adjusted models, OBS, dietary OBS, and lifestyle OBS were all negatively associated with the prevalence of CVD (odds ratios of 0.98, 0.98, and 0.85, respectively). Higher OBS and lifestyle OBS (p for trend 0.016 and <0.001, respectively) rather than dietary OBS (p for trend = 0.06) were associated with significantly lower odds of CVD. Higher OBS, dietary OBS, and lifestyle OBS were all negatively associated with all-cause mortality (hazard ratios [HR] of 0.98, 0.98, and 0.92, respectively; p for trend of 0.002, 0.009, and 0.035, respectively). Higher OBS and dietary OBS were negatively associated with CVD mortality (HR 0.96 and 0.95, respectively; p for trend both <0.001), whereas lifestyle OBS was not. Restricted cubic spline analysis suggested that most associations were linear. Stratified analyses showed that these associations were influenced by some demographic variables and disease status.

Conclusions: Adherence to higher OBS was associated with reduced CVD prevalence and mortality risk in T2D. Antioxidant diet and lifestyle had more significant associations with mortality and CVD prevalence, respectively. However, as these findings are merely associations and do not allow causal inferences to be drawn, future validation in high-quality randomized controlled trials is needed.

Background: Techniques for sperm cryopreservation have exhibited their potential in male fertility preservation. The use of frozen-thawed sperm in in vitro fertilization (IVF) cycles is widespread today. However, many studies reported that cryopreservation might have adverse effects on sperm DNA integrity, motility, and fertilization, probably due to cold shock, intra- and extracellular ice crystals, and excess reactive oxygen species (ROS). Studies suggested that freezing and thawing impaired sperm viability and might adversely affect subsequent fertilization and pregnancy outcomes. The potential damage to fertilization and subsequent embryonic development and offspring health raises the concern on sperm cryopreservation. However, the above mentioned studies are limited to intracytoplasmic sperm injection (ICSI) cycles, while IVF is a more natural and patient-friendly method. IVF requires a higher quality of sperm than ICSI. However, the effect of freezing and thawing on sperm used for IVF remains unknown. Therefore, we aim to investigate the effect of freezing and thawing on ejaculated sperm and subsequent pregnancy and neonatal outcomes in IVF.

Methods: This retrospective cohort study at a tertiary-care academic medical center included 447 women who used paternal frozen-thawed ejaculated sperm and 31,039 women who used paternal freshly ejaculated sperm for IVF and underwent frozen-thawed blastocyst transfer from January 2011 to September 2021. To balance the baseline characteristics of the two groups, patients using frozen sperm were matched with control groups using a propensity score matching algorithm with a ratio of 1:3.

Results: Although sperm motility decreased from 82.04% to 75.70% (P < 0.001) after the freezing-thawing process, the fertilization rate (68.27% for frozen sperm and 67.54% for fresh sperm), number of viable embryos (1.98 and 2.16), clinical pregnancy rate (44.7% and 51.8%), and live birth rate (40.3% and 42.4%) were comparable between the two groups (all P > 0.05). For neonatal outcomes, no between-group differences were observed in offspring gender, gestational age, birthweight, and the rate of preterm birth (21.7% and 12.9%), low birthweight neonates (19.2% and 16.0%), and birth defects (0.0% and 0.8%) (all P>0.05).

Conclusions: Frozen-thawed sperm had lower sperm motility but resulted in comparable embryonic, pregnancy, and neonatal outcomes versus fresh sperm in IVF cycles.

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder that increases fragility fracture risk. Conventional DXA-based areal bone mineral density (aBMD) assessments often underestimate this risk. Cortical Backscatter (CortBS) ultrasound, a radiation-free technique, non-invasively analyzes cortical bone's viscoelastic and microstructural properties. This study aimed to evaluate CortBS's discriminative performance in DM patients compared to DXA and characterize changes in cortical bone microstructure in Type 1 and Type 2 DM (T1DM, T2DM) patients.

Methods: This in-vivo study included 89 DM patients (T1DM = 39, T2DM = 48) and 76 age- and sex-matched controls. DXA measured aBMD, while CortBS measurements were taken at the anteromedial tibia using a medical ultrasound scanner with custom software. Multivariate analysis of variance assessed the impact of DM type on CortBS and DXA measurement results. Partial least squares discriminant analyses with cross-validation were used to compare the discrimination performance for vertebral, non-vertebral, and any fragility fractures, adjusting for gender, age, and anthropometric parameters (weight, height, BMI).

Results: Fractures occurred in 8/23 T1DM, 17/18 T2DM, and 16/55 controls. DXA parameters were reduced in fracture patients, with significant diabetes impact. T2DM was associated with altered CortBS parameters, reduced scatterer density, and larger pores. CortBS outperformed DXA in discriminating fracture risk (0.61 ≤ AUC(DXA) ≤ 0.63, 0.68 ≤ AUC(CortBS) ≤ 0.69).

Conclusions: Both T1DM and T2DM showed altered bone metabolism, with T2DM linked to impaired tissue formation. CortBS provides insights into pathophysiological changes in diabetic bone and provided superior fracture risk assessment in DM patients compared to DXA.