Endocrine Connections最新文献

Background: This systematic review seeks to employ a meta-analysis to evaluate the differential impacts of exercise interventions with high adherence versus those with low or uncertain adherence, following the American College of Sports Medicine (ACSM) guidelines, on factors such as glucose regulation and insulin sensitivity in prediabetic patients.

Methods: A thorough search was executed across databases such as PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 1, 2025. We carried out a meta-analysis concentrating on exercise interventions among prediabetic patients. Only randomized controlled trials were included in our study. The meta-analyses determined WMDs for parameters such as fasting blood glucose (FBG), 2-hour plasma glucose (2hPG), glycated haemoglobin A1c (HbA1c), and homoeostasis model assessment of insulin resistance (HOMA-IR).

Results: There were 24 studies with a total of 1,480 participants. Compliance with the ACSM recommendations was categorised as 'high' in 9 studies and 'low or uncertain' in 15 studies. In the subgroup analysis comparing high compliance with ACSM recommendations to low or uncertain compliance, the results were as follows: FBG: -0.55 (95% CI: -1.01, -0.09) vs -0.42 (95% CI: -0.62, -0.21), 2hPG: -0.97 (95% CI: -1.48, -0.45) vs -0.70 (95% CI: -1.15, -0.25), HOMA-IR: -0.47 (95% CI: -0.81, -0.14) vs -0.50 (95% CI: -1.09, 0.08), HbA1c:-0.20 (95% CI: -0.50, 0.10) vs -0.29 (95% CI: -0.46, -0.12).

Conclusion: Subgroup analyses were conducted to evaluate whether intervention adherence modifies the metabolic benefits of exercise. Mean reductions in FBG, 2hPG, and HOMA-IR were numerically larger in participants with high, compared with low or uncertain, adherence, suggesting a possible dose-response relationship between adherence and glycaemic improvement. Conversely, HbA1c displayed a marginally greater reduction in the low-adherence stratum - an observation that contrasts with the pattern seen for the other glucose/insulin indices. This discrepancy may reflect greater analytical variability of HbA1c, differences in intervention duration, baseline imbalance, or heterogeneity in programme content and individual responsivity across adherence categories. Large-scale, long-term trials that standardise the measurement of adherence and the delivery of exercise interventions are needed to definitively clarify the association between adherence and metabolic outcome.

Background: Bariatric surgery affects multiple physiological systems, including the regulation of des-acyl ghrelin (DAG). DAG has been negatively associated with excess adiposity and insulin resistance.

Objectives: To assess the relationship between serum DAG concentrations and short-term weight loss following bariatric surgery.

Setting: Prospective multicenter cohort study across three bariatric surgery centers in Latvia.

Methods: Fasting blood samples for DAG measurement were collected 1 day preoperatively, 2 days postoperatively, and at 3 months post-surgery. Anthropometric and laboratory assessments were performed at the same time points.

Results: A total of 62 patients were included; 64.5% (n = 40) underwent Roux-en-Y gastric bypass (RYGB), and 35.5% (n = 22) sleeve gastrectomy (SG). The cohort was predominantly female (67.7%). Median baseline weight and BMI were 129 kg (IQR 106-150) and 45.1 kg/m2, respectively. Median excess weight loss at 3 months was 40.2% (IQR 32.2-54.3%). DAG concentrations showed significant inverse correlations with preoperative weight (r = -0.371), BMI (r = -0.311), and excess weight (r = -0.355; all P < 0.05). These associations persisted across all sampling points in the RYGB group, whereas in SG patients, they were largely confined to postoperative day 2. No significant relationships were observed between DAG and relative weight-loss metrics. DAG levels were higher in females; age showed no association with DAG changes.

Conclusion: DAG levels are inversely associated with absolute measures of adiposity, particularly among RYGB patients. These findings support DAG's potential relevance as a marker of total fat burden and early postoperative metabolic response.

Objective: Hepatocyte growth factor (HGF)/c-MET signaling regulates glucose metabolism and tissue remodeling, but its role in gestational diabetes mellitus (GDM) remains unclear. We aimed to investigate maternal serum HGF and soluble c-MET (sc-MET) levels, their tissue expression in placenta and maternal visceral adipose tissue, and their associations with obstetric and perinatal outcomes in GDM.

Methods: In this retrospective observational, cross-sectional study, 76 pregnant women (32 GDM, 44 normal glucose tolerance) were enrolled. Serum HGF and sc-MET were measured by ELISA; placental and visceral-fat HGF/c-MET expression was analyzed by RT-PCR and western blot. Clinical variables, including umbilical-cord blood gas and glucose values, were evaluated.

Results: Maternal sc-MET levels were significantly higher, and cord-blood HGF levels significantly lower, in the GDM group. HGF protein expression was increased in maternal visceral fat but unchanged in placenta. Maternal HGF correlated negatively with cord base excess and positively with lactic acid levels, while cord HGF correlated positively with neonatal glucose.

Conclusions: These findings indicate tissue-specific dysregulation of HGF/c-MET signaling in GDM, potentially linking maternal insulin resistance with fetal metabolic stress through visceral-fat-derived HGF. The associations between maternal HGF and neonatal lactic acid levels suggest an endocrine interaction influencing fetal adaptation. Further studies are needed to clarify underlying mechanisms across heterogeneous GDM phenotypes.

Plain language summary: GDM is a condition that develops during pregnancy and affects how the body regulates sugar. This study explored how two proteins, HGF and its receptor c-MET, may influence metabolism in mothers with GDM and their babies. Blood, placenta, and visceral fat samples were analyzed from women with and without GDM. Mothers with GDM had higher blood levels of soluble c-MET and lower HGF levels in cord blood. HGF activity was increased in visceral fat, suggesting altered fat metabolism may contribute to insulin resistance. These changes were linked to higher lactic acid levels in newborns, a sign of metabolic stress. The findings suggest that HGF/c-MET signaling helps coordinate hormonal communication between mother and fetus during pregnancy and could serve as a potential biomarker for maternal insulin resistance and fetal metabolic health in GDM.

Objective: This study aims to identify potential drugs associated with diabetes insipidus (DI) and track its epidemiological characteristics using the FDA Adverse Event Reporting System (FAERS) database.

Methods: A retrospective pharmacovigilance analysis was conducted on FAERS data from Q1 2004 to Q4 2024. Disproportionality analyses were performed using the reporting odds ratio and the Bayesian confidence propagation neural network (BCPNN).

Results: A total of 2,189 cases of DI were recorded in FAERS, with a median age of 47.0 years (interquartile range (IQR) 27.0-60.0). Disproportionality analysis identified 71 drugs with positive signals, in which nervous system agents (22 drugs, 31.0%), antineoplastic agents (15 drugs, 21.1%), and systemic anti-infectives (14 drugs, 19.7%) constituted the top three drug classes. Lithium (n = 114, information component at the 95% lower credibility interval (IC025) = 6.12) and dexmedetomidine (n = 105, IC025 = 6.79) were identified as the most frequently reported drugs and showed the strongest association with DI. Several drugs, such as aripiprazole, letrozole, tigecycline, and dapagliflozin, were found to have unexpected potential associations with DI.

Conclusion: This study provides a comprehensive overview of drug-induced DI based on real-world data. It highlights the importance of monitoring patients for DI when using certain medications, particularly high-risk nervous system drugs and antineoplastic agents.

Background: This study investigates glucose metabolism changes in CG-IUGR rats and analyzes the potential underlying mechanisms. It identifies a critical warning period for glucose metabolism changes in CG-IUGR individuals from birth to adulthood, providing key intervention targets for the prevention and treatment of diabetes.

Methods: The CG-IUGR rat model was established by a low-calorie diet during pregnancy. Rats were measured weekly after birth for body length, weight, and BMI. Rats were assayed at 8-week-old for the following indicators. Serum fasting insulin (FINS) and insulin levels at 15 min after glucose load were detected. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were carried out. Skeletal muscle/liver glycogen content, glycogen synthase (GS) expression, and GS activity were assessed before and after glucose load.

Results: BMI and perirenal fat weight were significantly increased in CG-IUGR rats, showing catch-up growth. Serum FINS was decreased, whereas insulin at 15 min after glucose load was increased in CG-IUGR rats. GTT and ITT showed that CG-IUGR rats had significantly higher blood glucose levels at each time point after 15 min administration, suggesting their glucose intolerance and reduced insulin sensitivity. CG-IUGR rats manifested diminished skeletal muscle and liver glycogen content under basal conditions, accompanied by reduced GS expression and activity in these tissues. However, following a 15 min glucose challenge, a contrary trend was observed for all three parameters.

Conclusions: CG-IUGR rats have an increased susceptibility to DM. IUGR remodels glycogen synthesis in CG-IUGR rats, as demonstrated by the preferential storage of energy as glycogen.

Background: Maternal thyroid hormones have been shown to affect neonatal thyroid function. However, it remains unclear whether these associations persist across trimesters, and also little is known regarding the potential effects of mixtures.

Objective: This study aimed to examine the effects of maternal thyroid hormones as individual and as mixtures across three trimesters on neonatal thyroid stimulating hormone (TSH).

Methods: We included 2,139 pregnant women. Maternal thyroid hormones (TSH, free triiodothyronine (FT3), and free thyroxine (FT4)) across three trimesters and neonatal TSH level were measured. Multivariable linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations between maternal thyroid hormones (individual and mixtures) across three trimesters and neonatal TSH.

Results: Maternal TSH demonstrated the positive associations with neonatal TSH across three trimesters (first trimester: β = 0.112; 95% CI: 0.008, 0.215; second trimester: β = 0.122; 95% CI: 0.032, 0.212; third trimester: β = 0.115; 95% CI: 0.031, 0.200). Neonatal TSH was also positively associated with maternal FT4 in the third trimester (β = 1.313; 95% CI: 0.367, 2.239). Moreover, we found sex-specific associations, and the positive associations of maternal TSH and FT4 with neonatal TSH in the third trimester were observed only among female infants, while the positive association of maternal TSH with neonatal TSH in the second trimester was observed only among male infants. The overall positive associations of the mixtures were observed, and maternal TSH was identified as the major contributor.

Conclusion: Maternal thyroid hormones affect neonatal thyroid function across all three trimesters by fetal sex.

Objective: To investigate the clinicopathological correlation, prognostic significance, and risk model of SDHB expression loss and ERBB2 expression in pheochromocytomas and paragangliomas (PPGLs).

Methods: A total of 165 patients with histologically confirmed PPGLs who underwent surgery at the Cancer Hospital were enrolled. Clinical and pathological characteristics were retrospectively analyzed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) methods were employed, and data were analyzed and visualized using SPSS 25.0 and R Studio.

Results: Among the 165 patients (male-to-female ratio: 0.85:1; age range: 14-82 years), there were 117 cases of pheochromocytomas and 48 cases of paragangliomas. SDHB expression loss was detected in 29 patients, and SDHB expression retention was observed in 136 patients. ERBB2 overexpression was found in 47 patients and absent in 118 patients. A statistically significant correlation was observed between SDHB expression loss and ERBB2 expression (P < 0.001, R = 0.45). Survival analysis revealed significant differences in progression-free survival (P < 0.001) and overall survival (P < 0.001) between SDHB expression loss and SDHB expression retention PPGLs, as well as between ERBB2-overexpressing and low/non-expressing groups (PFS: P < 0.001; OS: P = 0.01). Univariate and multivariate COX regression analyses showed that SDHB expression loss was an independent prognostic factor for PFS. A three-tier risk prediction model based on four risk factors was established, with 5-year PFS rates of 91.5%, 41.7%, and 34.8% for low-risk, intermediate-risk, and high-risk groups, respectively (P < 0.001).

Conclusion: SDHB expression loss and ERBB2 overexpression are adverse prognostic factors in PPGL patients, and there may be a potential link between them. In addition, the risk prediction model established in this study confirms its predictive value for risk stratification in PPGL patients.

Significance statement: Studies on the correlation between SDHB expression loss and ERBB2 expression in PPGLs are still in a black stage, and a consensus on risk assessment for PPGL patients has not been reached. Therefore, these two aspects are the key objectives of our research. We investigated SDHB expression loss and ERBB2 expression at the protein level, exploring the correlation between them, conducting prognostic analysis, and establishing a risk model, in order to provide new diagnostic and therapeutic ideas and data support for the clinical management of PPGL patients.

Elabela (ELA) is a relatively newly identified bioactive micropeptide that functions as the second endogenous ligand for the apelin receptor (APJ). It plays a critical role in diverse physiological processes, including cardiovascular development, blood pressure regulation, and fluid homeostasis. Growing evidence underscores its significance in the pathophysiology of various organ systems, particularly the kidneys. This review aims to comprehensively explore the role of ELA in renal physiology and pathology. We focus on its molecular mechanisms, such as modulating renal hemodynamics, inhibiting fibrosis and inflammation, promoting cellular survival, and its therapeutic potential in acute kidney injury, chronic kidney disease, and hypertensive and diabetic nephropathy. Building upon our research group's previous work, this article places special emphasis on the role of ELA in renal metabolism and its promising application in the treatment of diabetic kidney disease. By synthesizing recent advancements, we seek to elucidate the connection between ELA and kidney health, assessing its potential as a novel therapeutic target for renal diseases.

Purpose: Steroidogenic factor 1 (SF-1), encoded by NR5A1, is essential for spleen development and function. NR5A1 variants have been linked to abnormal spleen development. Hyposplenism exposes individuals to severe complications with potentially serious sequelae. This study aimed to determine the prevalence and principal features of hyposplenism in a cohort of French patients with NR5A1 variants.

Methods: We conducted a cross-sectional multicentre ancillary study among 34 patients carrying heterozygous NR5A1 variants within the GR-EX cohort, which includes individuals from families affected by red blood cell diseases. All participants underwent splenic imaging (ultrasound, CT, or MRI) and pocked red blood cell (pRBC) quantification. pRBC thresholds of <7%, 7-20%, and >20% corresponded to normal splenic function, moderate hyposplenism, and severe hyposplenism, respectively. The primary endpoints were the prevalence of hyposplenism and its severity.

Results: Functional hyposplenism was observed in 21/34 patients (61.7%), including 16/34 (47%) with severe forms. Morphological spleen abnormalities were identified in 15/34 patients (44.1%), with asplenia in 4/34 (11.7%). All patients with morphological spleen abnormalities on imaging also presented functional hyposplenism. Conversely, 6/21 patients (28%) with functional hyposplenism showed no morphological abnormalities on imaging. No association was found between NR5A1 genotypes, gonadal phenotypes, and splenic anomalies.

Conclusions: Functional hyposplenism was frequent in this cohort of patients carrying NR5A1 variants, regardless of genotype and gonadal phenotype. Assessing splenic function is mandatory to help manage these patients. Preventive measures are also critical when hyposplenism is present.

The menopause transition represents a period of complex hormonal, metabolic, and psychosocial change that poses unique challenges for women living with type 1 diabetes mellitus (T1DM). Despite an expanding population of midlife women with T1DM, evidence to guide optimal menopause management remains limited. This narrative review synthesises current clinical and mechanistic evidence on the impact of menopause in women with T1DM. A literature search was conducted in MEDLINE (PubMed), the Cochrane Library, and professional society guidelines between January and May 2025. Across studies, women with T1DM appear to experience an earlier onset of menopause and an increased risk of osteoporosis, cardiovascular disease, psychological distress, metabolic deterioration and sexual dysfunction compared with women without diabetes. Oestrogen deficiency may exacerbate insulin resistance, dyslipidaemia, and vascular dysfunction, while glycaemic variability and altered insulin requirements are frequently reported during the menopause transition. Evidence regarding the safety and efficacy of hormone replacement therapy (HRT) in this group is sparse. In the absence of disease-specific data, clinicians should adopt an individualised approach - screening proactively for menopausal symptoms, bone loss, and cardiovascular risk, tailoring HRT decisions based on individualised risk profiles, and recommending transdermal oestradiol when HRT is used. This review highlights the urgent need for dedicated research, evidence-based guidelines, and integrated clinical pathways to optimise menopause management and long-term outcomes for women living with T1DM.