Frontiers in Endocrinology最新文献

Obesity is a global epidemic and a major risk factor for several non-communicable diseases. Systemic inflammation is believed to be involved in obesity and obesity-induced diabetes type 2, which alters adipose tissue homeostasis. Cytokines, the key mediators of inflammation, play a central role in this inflammatory state and have been extensively studied for their role in obesity and diabetes type 2. Therefore, blood and adipose tissue levels of cytokines have been a subject of intense investigation over the last two decades. Several studies reveal the role of cytokines and their profiles in the obese population. These studies have reported the significance of altered levels and patterns of several cytokines and their association with clinical parameters in obese and type 2 diabetics. This review examines population-based studies to evaluate whether cytokine profile consistently reflect chronic inflammation in obesity and type 2 diabetes. It highlights cytokines that show robust associations across ethnic and geographic cohorts. While majority of cytokines are frequently elevated in both conditions, their predictive value remains unclear. On the contrary we do find inflammatory cytokines like IL-1β which shows an association with diabetes type 2 but not obesity while IL-6 is more closely associated with obesity than diabetes. Anti-inflammatory cytokines IL-10 and IL-4 cannot be linked to either conditions. The study underscores the need for longitudinal and mechanistic studies to determine whether cytokine profiling could be used as an early diagnostic or prognostic tool.

Objectives: The aims of this study were to investigate the distribution of traditional Chinese medicine (TCM) constitution types in individuals with prediabetes and to identify high-risk constitutions, thereby providing an evidence-based foundation for the prevention and treatment of prediabetes.

Methods: We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, and four Chinese databases for literature examining the association between prediabetes and TCM constitution types. A single-proportion meta-analysis of cross-sectional studies and a comparative meta-analysis of case-control studies comparing individuals with prediabetes and the general population were performed using the Stata17.0 software. Effect sizes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Study quality was assessed independently by two reviewers. The primary outcomes included the distribution of TCM constitution types in the prediabetes population and the comparative ORs between groups.

Results: A total of 30 cross-sectional studies and 5 case-control studies, involving 8,469 participants, were included. Among individuals with prediabetes, the pooled prevalence rates of phlegm-dampness constitution (PDC), balanced constitution (BC), yin-deficiency constitution (YIDC), qi-deficiency constitution (QDC), and damp-heat constitution (DHC) were 20% (95% CI: 16%-24%), BC 16% (10%-22%), 12% (10%-15%), 11% (9%-14%), and 10% (7%-13%), respectively. Meta-analysis of case-control studies indicated that the ORs for prediabetes risk in individuals with PDC, qi-stagnation constitution (QSC), QDC, and YIDC were PDC 2.49 (95CI%: 1.27-4.87), 2.03 (1.06-3.90), 1.78 (1.11-2.84), and 1.52 (1.09-2.10), respectively, while the OR for BC was 0.45 (0.30-0.66). Subgroup analyses revealed variations in TCM constitution distribution across regions and age groups, as well as difference associated with study quality.

Conclusion: PDC, YIDC, QDC, DHC, and BC are the most common TCM constitution types (prevalence ≥10%) observed in individuals with prediabetes. PDC, QDC, YIDC, and QSC may represent risk factors for prediabetes, whereas BC appears to be a protective factor. Further high-quality case-control and cohort studies are warranted to strengthen the evidence regarding the relationship between prediabetes and TCM constitution types.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024607164.

Branched-chain amino acids (BCAAs) are a class of amino acids characterized by a branched aliphatic side chain, and they play critical physiological roles in humans, including protein synthesis, metabolic regulation, and immune system maintenance. Beyond serving as fundamental building blocks for protein biosynthesis, BCAAs and their metabolites also function as signaling molecules that regulate a variety of physiological processes, notably insulin secretion. Accumulating evidence indicates that plasma BCAAs levels are markedly elevated in patients with type 2 diabetes (T2DM), a phenomenon that may result from impaired activity of key enzymes in the BCAAs catabolic pathway, leading to metabolic dysregulation. It is widely recognized that BCAAs can activate the mTOR signaling cascade, thereby affecting insulin receptor sensitivity. In addition, aberrant BCAAs metabolism has been closely linked to alterations in the gut microbiota, which may further aggravate insulin resistance (IR). Taken together, dysregulated BCAAs metabolism may represent a critical mechanism underlying IR in T2DM. Therefore, this review summarizes current knowledge on BCAAs metabolism, explores its potential roles in the pathogenesis of IR in T2DM, and highlights emerging therapeutic strategies to reduce IR by targeting BCAAs metabolism.

Background: Cushing's disease (CD) is characterized by chronic hypercortisolism and is associated with persistent metabolic, psychological, and neurocognitive disturbances. While metabolic consequences are well described, the impact of disease activity and remission on eating behavior remains insufficiently explored.

Objective: This study aimed to compare multidimensional eating behavior patterns among patients with active Cushing's disease, patients in biochemical remission, and healthy controls, and to examine their associations with cortisol biomarkers.

Methods: In this cross-sectional study, 74 participants were enrolled, including patients with active CD (n = 21), patients in remission (n = 32), and age-, sex-, and BMI-matched healthy controls (n = 21). Eating behavior was assessed using validated questionnaires: the Night Eating Questionnaire (NEQ), Emotional Appetite Questionnaire (EMAQ), Three-Factor Eating Questionnaire-Revised 18 (TFEQ-R18), Mindful Eating Questionnaire (MEQ), and Dutch Eating Behavior Questionnaire (DEBQ). Group differences were analyzed using Kruskal-Wallis tests followed by Dunn's post-hoc comparisons with Bonferroni correction. Associations between eating behavior scores and cortisol parameters were evaluated using Spearman correlation analysis.

Results: Active Cushing's disease was associated with higher night eating (NEQ; p < 0.001) and greater emotional and situational eating compared with remission and healthy controls (EMAQ total; p < 0.001). Positive emotion and situation subscales were higher in active disease (both p = 0.008), whereas negative total scores differed significantly only between active disease and healthy controls (p = 0.014). Mindful eating was reduced in both patient groups versus controls (MEQ total; p < 0.001), with active disease showing higher disinhibition (p = 0.002), greater interference (p < 0.001), and lower conscious nutrition (p = 0.016). Remission patients demonstrated partial but incomplete behavioral recovery. Late-night salivary cortisol correlated with MEQ interference (r = 0.5, p = 0.01), and cortisol levels after the 1-mg DST correlated with DEBQ emotional eating (r = 0.5, p = 0.01).

Conclusion: Cushing's disease is associated with marked alterations in eating behavior, particularly during active disease, including increased night eating, emotional susceptibility, and reduced mindful regulation. Although partial improvement occurs after remission, residual behavioral disturbances persist. These findings underscore the importance of integrating behavioral assessment into the long-term management of Cushing's disease.

Aims: To evaluate the differences in xanthine oxidoreductase (XOR) activity, metabolomic profiles, markers of oxidative stress, and inflammatory factors between patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and healthy controls, as well as the correlations among these factors.

Methods: A case-control study was conducted involving 54 MASLD patients alongside 54 healthy controls who were matched for age, gender, and ethnicity. Participants underwent comprehensive blood biochemical testing, including liver function, kidney function, glucose, lipid, XOR activity, markers of oxidative stress, and inflammatory factors. Non-targeted metabolomics detection was conducted to identify alterations in the metabolites of MASLD patients.

Results: MASLD patients showed significantly elevated levels of XOR activity, and this increase was positively correlated with significantly altered markers of oxidative stress and inflammatory factors, including increased malondialdehyde levels, tumor necrosis factor-α and interleukin-6. Metabolomic analysis revealed a unique pattern of specific metabolites, including animo acids, sphingolipids, phospholipids, and fatty acids, which were significantly altered in MASLD. A total of 100 metabolites were identified as differentially expressed between MASLD and control groups, with 44 metabolites specifically associated with XOR activity. These metabolites were significantly correlated with lipid profiles, oxidative stress indices, and inflammatory factors.

Conclusion: This study demonstrates significant alterations in XOR activity, lipid metabolism, oxidative stress, and inflammatory reactions in MASLD, as well as the significant association between these factors.

Objective: Ovarian aging is an inevitable age-associated biological phenomenon.Enhancing clinical pregnancy outcomes in women with advanced maternal age (AMA) has emerged as a critical research priority in reproductive medicine. The current study seeks to unravel the mechanism governing mitochondrial energy metabolism reprogramming in granulosa cells (GCs) during age-associated ovarian aging.

Methods: We conducted an age-stratified prospective observational study involving GC samples from 10 young infertile women (young group: 21-34 years) and 10 infertile women with AMA (AMA group: 35-42 years), all undergoing in vitro fertilization-embryo transfer (IVF-ET). Participants were recruited from November 2023 to November 2024. Additionally, an in vitro oxidative stress-induced senescence model was established using hydrogen peroxide (H₂O₂)-treated human ovarian granulosa-like tumor cell line (KGN cells) to further investigate metabolic disturbances and mitochondrial reactive oxygen species (mtROS) levels in senescent GCs.

Results: High-resolution targeted metabolomics revealed 25 statistically significant metabolite alterations in ovarian GCs, indicating profound dysregulation of core energy metabolism pathways-particularly oxidative phosphorylation (OXPHOS), glycolysis, and the tricarboxylic acid (TCA) cycle. Compared to the young group, the AMA group exhibited upregulated glycolytic metabolites alongside downregulated OXPHOS and TCA cycle intermediates. These findings were further validated in an H₂O₂-induced KGN cells senescence model, where treated cells demonstrated: (1) increased senescence-associated β-galactosidase (SA-β-gal) activity, (2) elevated extracellular acidification rate (ECAR) and lactate (Lac) production, (3) reduced oxygen consumption rate (OCR), (4) depleted glucose and pyruvate(Pyr) pools, and (5) heightened mtROS generation relative to control group.

Conclusions: Collectively, our research demonstrates that GCs undergo mitochondrial energy metabolism reprogramming, characterized by a metabolic shift from OXPHOS to glycolysis, during ovarian aging. These observations suggest that age-associated glycometabolic perturbations may represent a novel therapeutic target for infertility in women with AMA.

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroiditis characterized by thyroid-specific autoantibodies (TPOAb, TGAb) positivity and lymphocytic infiltration, and is a major cause of hypothyroidism in iodine-sufficient regions. Epidemiological data show a significant increase in the prevalence of HT, which is about four times more common in adult women than in men. The pathogenesis of HT involves a complex interaction of genetic susceptibility, environmental factors, and immune regulation. Its clinical diagnosis is mainly based on serological tests (TPOAb/TGAb) and thyroid ultrasound features. The current treatment of Hashimoto's is based on levothyroxine (T4) replacement. This article presents a narrative review of the pathogenesis, status, and challenges of treatment of HT to provide a theoretical basis for optimizing clinical practice and basic research.

Introduction: Kidney stones are a common disorder with increasing global prevalence. Metabolic dysfunction-associated steatotic liver disease (MASLD), a systemic metabolic condition, has been suggested to be linked with kidney stones, but existing evidence is inconsistent. This study aimed to clarify the association between MASLD and kidney stones risk using both cross-sectional and cohort analyses.

Methods: A total of 1,875 participants from a cross-sectional study and 1,903 from a community-based cohort were analyzed. Logistic regression was used in the cross-sectional study, while incidence rates, Kaplan-Meier curves, log-rank tests, and Cox models estimated risk in the cohort. Subgroup and mediation analyses were performed, with METS-IR, WBC, and eGFR examined as mediators.

Results: In the cohort study, there were 94 incident kidney stone cases identified during a median follow-up of 34.62 months, with an incidence rate of 17.6 per 1,000 person-years. In the cross-sectional analysis, MASLD was positively associated with kidney stones, with an odds ratio (OR) of 1.466 (95% CI: 1.059-2.028) after adjustment for potential confounders. Kaplan-Meier analysis revealed significant differences in cumulative incidence between MASLD and non-MASLD groups (log-rank P < 0.001). Cox regression confirmed MASLD as an independent risk factor for kidney stones (HR = 2.04, 95% CI: 1.29-3.23). Subgroup analyses showed consistent associations in metabolically high-risk individuals. Mediation analyses further highlighted METS-IR as a key mediator linking MASLD to kidney stone formation.

Conclusions: MASLD was independently associated with increased kidney stone risk, particularly in metabolically high-risk individuals. METS-IR mediated this relationship, underscoring the critical role of insulin resistance.

Background: Severe hypocalcemia in children can precipitate life-threatening neurologic and cardiovascular events, including seizures and cardiac dysfunction. Etiologies range from nutritional deficiency to genetic syndromes, yet local epidemiologic and clinical data remain limited, particularly in Southeast Asia.

Methods: We retrospectively reviewed 246 children (newborns to 18 years) admitted with severe hypocalcemia at the Vietnam National Children's Hospital (2018 - 2024), the leading tertiary center in Northern Vietnam. Demographic, clinical, and comprehensive biochemical data were collected. Descriptive, bivariate, and multivariable logistic regression analyses identified independent predictors of major clinical outcomes.

Results: Among 246 children, infants and young children predominated (70.7%; median age 67 days). Seizures occurred in 79.2%, while vitamin D deficiency (67.1%) and hypoparathyroidism (28.0%) were the leading causes of severe hypocalcemia. The mean ionized calcium level was profoundly low (0.66 ± 0.13 mmol/L). Patients with vitamin D deficiency had markedly low 25(OH)D levels (mean 18.4 nmol/L) and high PTH (mean 261.7 pg/mL), consistent with secondary hyperparathyroidism. Conversely, those with hypoparathyroidism showed low PTH levels (22.2 pg/mL) despite significant hypocalcemia. Children with DiGeorge syndrome had even lower PTH levels (6.3 pg/mL) and preserved phosphate. In multivariate analyses, lower ionized calcium and lower 25-hydroxyvitamin D levels were independent predictors of seizures. Cardiac complications (cardiogenic shock and/or acute heart failure) occurred in 5.7% and were associated with more severe hypocalcemia.

Conclusion: Severe pediatric hypocalcemia in Vietnam predominantly affects infants and young children and is largely attributable to preventable vitamin D deficiency. While vitamin D deficiency is globally recognized, this study provides novel region-specific insight into the high frequency of symptomatic presentations, including seizures and cardiac events, in a tropical setting with presumed adequate sunlight exposure. It also emphasizes distinct biochemical phenotypes that allow early etiological stratification. These findings reinforce the urgency of proactive vitamin D supplementation policies and biochemical screening protocols tailored for high-risk populations, particularly in resource-limited settings.

Background: The temporal dynamics of sleep disturbances following radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC), along with their underlying mechanisms and associated factors, remain poorly understood. This gap underscores the need for longitudinal investigations.

Methods: We conducted a longitudinal study of 160 DTC patients from Guangdong Southern Teaching Hospital. Self-assessment scales were used to assess patients' knowledge of the purpose of ¹³¹I therapy, depression, anxiety symptom and sleep assessment scales were used to assess with the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). Assessments were conducted at three time points: pre-therapy, peri-therapy (during hospitalization), and post-therapy.

Results: Of the 160 patients, 148 completed the study (53 males [35.8%]; 95 females [64.2%]). Risk factors associated with sleep disorders included anxiety, snoring, educational level, and work/study-related stress. Longitudinal trajectory analysis revealed nonlinear trends: the incidence of sleep disorders (35.8% → 52.9% → 32.6%), anxiety symptoms (23.6% → 40.7% → 14.0%), and depressive symptoms (47.3% → 56.4% → 33.3%) all increased initially before declining.

Conclusion: With increasing treatment duration, the incidence of sleep disorders, anxiety, and depression initially rose and subsequently declined. Sleep quality reached its lowest point at the end of treatment, whereas anxiety and depression levels peaked one month post-therapy before decreasing to levels below the pre-treatment baseline.