Frontiers in Endocrinology最新文献

Background: Metformin is widely used as a first-line therapy for type 2 diabetes and increasingly prescribed off-label in women with elevated HOMA-IR indices, including those at risk of metabolic disorders. However, its clinical use is often limited by gastrointestinal (GI) adverse effects. The present study examined whether a multi-strain probiotic could enhance the metabolic effects of metformin and reduce GI side effects in women with newly identified elevated HOMA-IR.

Methods: In this 12-week randomised, placebo-controlled, double-blind trial, 30 women aged 25-45 years with elevated HOMA-IR (≥2.5) and no diagnosis of diabetes were enrolled. All participants were prescribed metformin 1000 mg/day. They were randomised 1:1 to receive either a multi-strain probiotic (2 × 10⁹ CFU/day) or placebo. Outcomes included metabolic markers (glucose, insulin, HOMA-IR, RBP4, lipid profile, body composition) and self-reported GI symptoms.

Results: After 12 weeks, the probiotic group reported significantly fewer GI symptoms compared with placebo, including lower frequency of abnormal stool consistency during abdominal pain (26% vs. 52%, p < 0.05), abnormal stool frequency (18% vs. 51%, p < 0.05), and hard or lumpy stools (Bristol types 1-2; 14% vs. 26%, p < 0.05). No significant between-group differences were observed for metabolic or anthropometric parameters. Both groups showed significant improvements over time in fasting glucose (time effect p < 0.05), HOMA-IR (p < 0.05), RBP4 (p < 0.05), and total cholesterol (p < 0.01), with no significant group × time interactions, indicating effects attributable to metformin rather than probiotic supplementation.

Conclusion: Multi-strain probiotic supplementation did not enhance the metabolic efficacy of metformin in women with elevated HOMA-IR but significantly alleviated GI side effects. Probiotic co-administration may therefore improve tolerability and adherence to metformin therapy.

Clinical trial registration: https://clinicaltrials.gov/study/NCT06092060, identifier NCT06092060.

Background: Overweight and obesity in adolescents has become a new worldwide health problem. Overweight in adolescence not only leads to persistent overweight and even obesity in adulthood, but also leads to decreased arterial function in adolescence and a greatly increased incidence of chronic diseases in adulthood. However, current imaging techniques cannot detect the early decrease of arterial elasticity. In this study, Ultrafast pulse wave velocity (UFPWV) technology was used to quantitatively evaluate the carotid artery elasticity in adolescents with simple overweight. In order to find the changes of carotid artery elasticity and related influencing factors in overweight adolescents at an early stage.

Data and methods: A total of 56 adolescents who met the inclusion and exclusion criteria were enrolled in this study, including 30 adolescents with Body mass index (BMI) ≥24kg/m² as overweight group and 26 adolescents with normal clinical signs and examinations as normal group. Clinical data and biochemical parameters were collected and analyzed for all participants, along with measurements of carotid intima-media thickness (IMT) and carotid arterial elasticity, including pulse wave velocity at the beginning of systole (PWVBS) and at the end of systole (PWVES).

Results: The mean values of IMT, PWVBS and PWVES in overweight group were higher than those in normal group. There was significant difference between PWVBS and PWVES (P< 0.05), but not IMT (P >0.05). PWVBS and PWVES in overweight group were positively correlated with BMI, uric acid (UA), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (all P< 0.05). And negatively correlated with High-density lipoprotein cholesterol (HDL-C) (P< 0.05). Within the overweight group, the subgroup with elevated uric acid (UA) levels showed significantly higher arterial elasticity parameters compared to the subgroup with normal UA levels (P < 0.05), whereas no statistically significant difference was observed in IMT between the two subgroups (P > 0.05). Receiver operator characteristic curve (ROC) analysis showed that when PWVES>4.515 m/s was used as the cut-off value of abnormal carotid elasticity in overweight adolescents in this study, the sensitivity was 71.8%. The specificity was 73.2%.

Conclusion: UFPWV can detect early changes in carotid artery elasticity in overweight adolescents. When hyperlipidemia and hyperuricemia coexist, they exert a synergistic detrimental effect on arterial elastic function. The arterial elasticity indexes PWVBS and PWVES are significantly correlated with a variety of traditional risk factors of atherosclerosis (AS), which can be used AS effective indicators to predict early AS.

Background: Positron emission tomography (PET) of the adrenal glands emerged as a non-invasive alternative to adrenal vein sampling (AVS) for treatment selection in primary aldosteronism (PA). The C-X-C-chemokine-receptor type 4 targeting tracer [⁶⁸Ga]PentixaFor showed potential in visualizing aldosterone-producing adenomas. However, standardized diagnostic criteria and experience in European cohorts remain scarce. Here, we report harmonized PET/CT interpretation criteria, assess their impact on diagnostic agreement, and present a large European tertiary center's experience with [⁶⁸Ga]PentixaFor PET/CT in PA.

Methods: Between 11/2023 and 01/2025, 35 consecutive PA patients underwent [⁶⁸Ga]PentixaFor PET/CT; 22 also underwent AVS. PET/CT scans were interpreted in three independent, blinded reads, in which inter-reader agreement was assessed: (i) the routine clinical read by the local team, (ii) an independent review by external molecular imaging experts, (iii) a local re-evaluation using harmonized criteria adapted from experience with [¹¹C]Metomidate PET. Surgical outcomes were analyzed according to Primary Aldosteronism Surgery Outcome (PASO) criteria.

Results: Agreement between local and external readings was 80% (28/35), increasing to 94% (33/35) after applying harmonized PET/CT criteria. Based on local readings, 18/35 scans (51%) were interpreted as unilateral. In contrast, both the external review and the local team's re-evaluation classified 11/35 (31%) as high probability, and 10/35 (29%) as intermediate probability of unilateral PA. According to local AVS criteria, 10/14 interpretable AVS indicated unilateral disease, with 8/10 concordant on PET. Combining successfully and partially cannulated AVS with PET findings, high confidence to diagnose unilateral disease increased to 12/22 (55%) patients. Twelve patients underwent adrenalectomy with PASO outcomes assessed ≥ 6 months after surgery, identified by AVS, PET or both (n=3, n=8 and n=1, respectively). Complete biochemical remission occurred in 2/3 operated patients based on AVS, 6/8 operated patients informed by PET, and 1/1 guided by both.

Conclusion: [⁶⁸Ga]PentixaFor PET continues to show promise for non-invasive PA subtyping. Harmonized interpretation criteria substantially improved inter-reader agreement. When combined with (partial) AVS, PET increases diagnostic confidence and may expand access to definitive treatment. Further studies are warranted to validate the proposed PET interpretation criteria and better define the subset of patients in whom [⁶⁸Ga]PentixaFor PET/CT alone might suffice for PA subtyping.

Male infertility accounts for nearly half of all infertility cases worldwide, yet up to 30-40% of affected men remain categorized as 'idiopathic', reflecting limitations of conventional diagnostics such as semen analysis, hormonal profiling, karyotyping, and Y-chromosome microdeletion testing. These methods describe sperm quantity and morphology but fail to uncover underlying molecular dysfunctions. Increasing evidence suggests that oxidative stress plays a central role in driving sperm damage, encompassing lipid peroxidation, protein oxidation, mitochondrial dysfunction, DNA fragmentation, and epigenetic instability. Such diverse pathways highlight the inadequacy of a single idiopathic category and necessitate mechanistic stratification. This evidence-based study proposes redox endophenotypes, including hyper- and hypo-oxidative, DNA damage-dominant, mitochondrial dysfunction, epigenetic-redox, and inflammatory-redox phenotypes, as a framework for reclassifying idiopathic male infertility. Each phenotype integrates specific biomarkers, such as oxidation-reduction potential (ORP), isoprostanes, 8-hydroxy-2'-deoxyguanosine, or advanced oxidation protein products, with distinct functional impairments and clinical outcomes. Redox endophenotyping offers diagnostic refinement, guides personalized antioxidant or adjunctive therapy, and informs clinicians and embryologists for appropriate assisted reproductive technology (ART) protocols by counselling and treating the patient, and tailoring sperm selection and preparation strategies. Future directions include multi-center validation of redox assays, integration with omics and exposome data, and application of artificial intelligence for biomarker-driven algorithms. Recognizing redox endophenotypes not only reduces the reliance on exclusionary 'idiopathic' diagnoses but also advances precision andrology, improving patient diagnostics and care, reproductive outcomes and mitigating intergenerational health risks.

Osteoporosis is an increasingly important global health concern, particularly in aging populations, with prevalence rising markedly after the age of 60. Age-related alterations in the bone microenvironment play a pivotal role in disrupting skeletal homeostasis. Regulators of the bone microenvironment contribute centrally to osteoporosis pathogenesis by modulating bone remodeling through multiple, intersecting mechanisms. Accumulating evidence indicates that aging is accompanied by reduced levels of protective factors, such as osteoprotegerin and bone morphogenetic proteins (BMPs), alongside increases in pro-resorptive mediators, including receptor activator of nuclear factor-κB ligand (RANKL), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). This shift favors osteoclastogenesis and impairs osteoblast function, ultimately accelerating bone loss and increasing the risk of fragility fractures and disability. In this review, we synthesize current evidence on bone microenvironment regulatory factors in osteoporosis, with emphasis on their roles in bone remodeling and downstream cellular signaling pathways. We further discuss emerging intervention strategies that target these regulators to preserve or restore bone health in older adults. By clarifying age-associated microenvironmental changes and the interactions among key regulatory factors, this review aims to identify promising therapeutic targets and provide a conceptual framework to support osteoporosis prevention and treatment in the context of global population aging.

Background: Diabetic retinopathy (DR) is a common chronic complication of diabetes mellitus. Endothelin-1 (ET-1) has been identified as a key regulator of various ocular functions, including vascular perfusion, aqueous humor dynamics, and retinal ganglion cell survival. Substantial evidence further underscores the critical involvement of ET-1 in the pathogenesis and progression of DR. Elevated ET-1 levels have been reported in patients with DR; however, findings across studies are inconsistent.

Aim: This meta-analysis aimed to statistically evaluate the level of ET-1 in patients with DR.

Methods: A systematic literature search was conducted across five electronic databases (PubMed, Web of Science, OVID, Elsevier Science Direct, and Wiley Online Library). The search strategy targeted the terms "Endothelin-1" or "ET-1" in conjunction with "Diabetic retinopathy" or "DR" in title and abstract fields. Results are presented as standardized mean differences (SMD) with 95% confidence intervals (CI).

Results: Ten articles (346 cases and 425 controls) were included in the meta-analysis. The results of the meta-analysis indicated that the circulating ET-1 in patients with DR was significantly higher than that of the controls (SMD: 1.73, 95% CI: 0.90, 2.56). Furthermore, circulating ET-1 in patients with DR was also significantly higher than those in healthy individuals or diabetic patients without retinopathy, respectively.

Conclusions: This meta-analysis is the first to systematically assess ET-1 levels in patients with DR. The findings of this study indicate the potential application of ET-1 as a biomarker for monitoring DR progression.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251156225.

[This corrects the article DOI: 10.3389/fendo.2025.1671046.].

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), recently redefined from non-alcoholic fatty liver disease, commonly coexists with type 2 diabetes mellitus and may adversely affect skeletal health through inflammation and insulin resistance. However, research on site-specific bone mineral density (BMD) effects in South Asian populations, particularly Indians, remains limited. This study aimed to evaluate the association between MASLD and BMD at different skeletal sites among adults with type 2 diabetes mellitus in North India.

Methods: This cross-sectional study included 100 adults (50 with T2DM and 50 controls) at a tertiary care center in Jaipur, India. MASLD was evaluated using the fibrosis-4 (FIB-4) index, hepato-renal index, and two-dimensional shear wave elastography. BMD at lumbar spine (L1-L4), left total hip (proximal femur), and left forearm was assessed by dual-energy X-ray absorptiometry. Associations between MASLD parameters and BMD were analyzed using multivariable linear regression, adjusting for age, sex, and smoking status.

Results: T2DM patients showed significantly lower lumbar spine (L1-L4) BMD (0.93 vs. 0.98 g/cm²; P = 0.026) and T-scores (-1.33 vs. -0.72; P = 0.004), especially in males ≥50 years. No statistically significant differences were observed in proximal femur and forearm BMD between groups. FIB-4 scores were higher (P = 0.004), with 60% at intermediate-to-high fibrosis risk versus 28% of controls; advanced fibrosis occurred in 10% vs. 2%. Hepatic steatosis positively associated with hip BMD (β=0.738; P = 0.022).

Conclusion: This study establishes significant, site-specific associations between MASLD and reduced bone mineral density in type 2 diabetes mellitus patients, particularly affecting trabecular-rich skeletal sites. The complex relationship between hepatic steatosis and skeletal health highlights the multisystemic nature of metabolic dysfunction. These findings support integrating bone health assessments and non-invasive hepatic fibrosis screening into routine diabetes care to improve early risk stratification.