Background Recent studies suggest that the development of prediabetes and its associated comorbidities may depend on sex and reproductive status. While the exact mechanism is unclear, differences in insulin sensitivity, body fat distribution, and glucose and lipid metabolism may play a role. In this study, we investigated how sex differences in metabolic and inflammatory parameters affect the development of prediabetic conditions in a non-obese rat model with severe dyslipidaemia. Methods Wistar Kyoto (WKY) rats served as the control group, while age-matched Hereditary Hypertriglyceridaemic (HHTg) rats were used as a non-obese, prediabetic model with genetically determined hypertriglyceridaemia, insulin resistance and impaired glucose tolerance. Results Compared to WKY controls, the HHTg strain exhibited increased serum triacylglyceroles (TAG) as well as ectopic TAG accumulation in the liver, heart and skeletal muscle which was more pronounced in HHTg females. However, this higher ectopic TAG accumulation in HHTg females was not associated with increased lipotoxic diacylglyceroles. The HHTg strain showed increased visceral adiposity, which was distributed differently: HHTg females had increased perimetrial adipose tissue, while HHTg males had increased perirenal adipose tissue. Impaired insulin sensitivity was observed in both sexes of the HHTg strain in skeletal muscle and adipose tissue. Insulin resistance in the HHTg strain may be due to elevated leptin and NEFA levels, as well as decreased GLUT4 in skeletal muscle. In addition, the HHTg strain showed impaired glucose tolerance, as well as hyperinsulinaemia, which was more pronounced in HHTg males. Increased lipogenesis ( mRNA Scd1 ), oxidative stress (decreased SOD activity) and inflammation ( mRNA Tnfα) in the liver may contribute to the development of hepatic steatosis and hepatic lipid accumulation. In visceral adipose tissue, increased mRNA Hif1 may contribute to adipose tissue hypoxia and impair insulin sensitivity, particularly in males. Conclusions Despite having more pronounced dyslipidaemia, ectopic lipid accumulation, and visceral adiposity, prediabetic females have better glucose tolerance and insulin sensitivity markers than prediabetic males. These sex differences may be due to variations in fat distribution, lipid metabolism and chronic inflammation. Our findings suggest that males are more susceptible to developing early prediabetic damage, such as insulin resistance and fatty liver, regardless of obesity.

Objective To investigate the role of early pregnancy thyroid function in gestational diabetes mellitus (GDM) development and its influencing factors. Methods This large-scale retrospective cohort study assessed the associations between early pregnancy thyroid hormones and GDM subtypes, as well as their non-linear relationship with oral glucose tolerance test (OGTT) glucose levels, using multivariate logistic regression and restricted cubic spline models. Subgroup analyses were conducted within the normal thyroid function range to evaluate the risk associated with low-normal FT4 levels. Results A total of 40,682 pregnant women were included and classified into four groups based on glucose levels: isolated fasting hyperglycemia (IFH), isolated post-load hyperglycemia (IPH), combined hyperglycemia (CH), and normal glucose tolerance (NGT). Free thyroxine (FT4) showed strong capability in differentiating among the subtypes, while thyroid-stimulating hormone (TSH) had limited effects. Multivariate and non-linear analyses showed a J-shaped association between FT4 and fasting/1-hour OGTT glucose, with strong protection below 15.4 pmol/L. In contrast, TSH showed weaker associations without a clear threshold effect. Importantly, low-normal FT4 (11.6–15.4 pmol/L), even within the normal range, independently increased GDM risk, especially in nulliparous and overweight/obese women. Conclusion FT4 is an independent risk factor for GDM, with parity and pre-pregnancy BMI serving as important effect modifiers. Even the low-normal FT4 levels are associated with a higher risk of developing GDM and macrosomia.

Objective The role of intrauterine PRP infusion in managing recurrent implantation failure (RIF) remains controversial despite its emerging clinical use. This systematic review aims to evaluate its therapeutic potential in RIF patients and further to investigate variations in outcomes based on transfer cycle type, embryo developmental stage, RIF diagnostic criteria, and endometrial thickness. Methods We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) investigating PRP treatment for RIF patients from the beginning of the database to May 2025. Results This meta-analysis showed that PRP administration significantly improved clinical pregnancy rate (CPR) [OR = 3.18, 95%CI (2.45, 4.14), I 2 = 3%], biochemical pregnancy rate (BPR) [OR = 2.84, 95%CI (2.22, 3.63), I 2 = 0%], ongoing pregnancy rate (OPR) [OR = 3.41, 95%CI (2.08, 5.60), I 2 = 30%] and live birth rate (LBR) [OR=5.10, 95%CI (1.95, 13.37), I 2 = 75%] in women with RIF. However, PRP intrauterine infusion did not reduce miscarriage rate (MR). Notably, the preterm birth rate was significantly higher in the PRP group compared to controls [OR = 8.24, 95%CI (2.09, 32.41), I 2 = 0%]. Subgroup analysis demonstrated that PRP improved CPR, BPR and LBR in both the fresh and frozen embryo transfer cycles. Additionally, while PRP increased CPR, LBR and reduced MR in blastocyst transfers [CPR OR = 3.84, 95%CI (2.82, 5.23), I 2 = 0%; LBR OR = 7.32, 95%CI (3.17, 16.90), I 2 = 63%; MR OR = 0.27, 95%CI (0.07, 0.96), I 2 = 54%], these effects were not observed in cleavage-stage embryo transfers. Moreover, PRP administration associated with a higher CPR [OR = 3.84, 95%CI (2.82, 5.23), I 2 = 0%], OPR[OR = 4.13, 95%CI (1.79, 9.56), I 2 = 48%], LBR [OR = 7.32, 95%CI (3.17, 16.90), I 2 = 63%] and a lower MR [OR = 0.27, 95%CI (0.07, 0.96), I 2 = 54%] in women with ≥3 prior implantation failure, it did not confer the same benefit to those with a history of ≥2 failed cycles. Conclusion These findings suggest a possible beneficial role for PRP on pregnancy outcomes to some extent in women with RIF, particularly in cases with ≥3 prior failed transfers, and blastocyst transfer may increase LBR and reduce miscarriage risk. However, further investigation is warranted to determine whether this treatment may pose an increased risk of preterm birth. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251061511.

Background The accumulation of visceral fat is a pivotal factor in the development and progression of Cardiovascular-Kidney-Metabolic (CKM) Syndrome. The early identification of high-risk individuals is crucial for delaying disease progression. The body roundness index (BRI) is a novel measures for assessing visceral fat, but its association with CKM-related outcomes lacks comprehensive evidence. Methods A comprehensive literature search was conducted to identify observational studies that examined the association between BRI and CKM-related outcomes. The search was performed in PubMed, Web of Science, and Embase, and updated to July 7, 2025. Effect sizes were pooled using a random-effects model, with heterogeneity and publication bias evaluated. Additionally, a diagnostic meta-analysis was performed to assess the discriminatory ability of BRI for specific metabolic risk factors. Results A total of 93 studies (involving 13 countries) were included. BRI was significantly associated with the risk of multiple CKM-related outcomes, but its strength varied by outcome and gender subgroup. For metabolic syndrome, BRI exhibited consistent risk associations in the overall population and gender subgroups, with good discriminatory ability in the diagnostic meta-analysis. However, its predictive ability for chronic kidney disease, cardiovascular disease, and mortality was relatively constrained. Conclusion Within the CKM framework, a significant association between BRI and the risk of multiple CKM-related outcomes has been identified, with favorable risk assessment and discriminatory performance of BRI observed, especially for metabolic abnormalities. As a complementary tool to conventional anthropometric indices, BRI can provide incremental information to optimize the identification and risk stratification of CKM-related risks. Further definition of the long-term predictive value and clinical utility of BRI across diverse global populations is warranted through high-quality prospective cohort studies. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/ , identifier CRD420251110973.

Objective This study aimed to evaluate the effect of a 50% reduction in preprandial bolus insulin (50%-B) on plasma glucose (PG) responses during postprandial exercise of continuous moderate intensity (CONT) and intermittent high intensity (INT) in individuals with type 1 diabetes (T1D). Methods Sixteen adults with T1D (31% male), treated with multiple daily insulin injections (MDI), participated in a randomized crossover study comprising four experimental conditions, separated by a washout period of at least 48 hours. Participants performed two 30-minute, preceded by a 3-minute warm-up without weights: • CONT: continuous cycling at 60% of maximal aerobic power (MAP). • INT: 2-minute intervals alternating between 40% and 80% of MAP, repeated for 7 intervals, with the last interval adjusted so that the total exercise time is exactly 30 minutes. Each exercise modality was performed under two insulin conditions: a full preprandial bolus (100%-B) and a 50% reduction (50%-B). Plasma glucose, insulin, and cortisol were measured before, during, and after exercise. Linear mixed models were used to analyze temporal changes and condition effects. Results Blood glucose decreased significantly over time for both exercise types (p < 0.001). During CONT, the decline in PG was similar between doses (Δ100%-B: –3.01 ± 2.96 vs. Δ50%-B: –2.82 ± 2.28 mmol/L; p = 0.18), However, the nadir PG was higher with 50%-B compared to 100%-B (8.59 ± 4.07 vs. 5.69 ± 3.06 mmol/L, respectively; β = +2.91 mmol/L; p = 0.026), and hypoglycemia was less frequent (2 vs. 18 episodes; p = 0.028). During INT, PG decreased less with 50%-B than with 100%-B (Δ: –2.03 ± 1.63 vs. –3.62 ± 2.76 mmol/L; p = 0.022), with no hypoglycemic episodes under 50%-B compared to six with 100%-B. Mean PG remained higher with 50%-B across both exercise types (p < 0.01). Plasma insulin decreased over time (p = 0.038) regardless of bolus condition, while cortisol increased more during INT with 100%-B than with 50%-B (p = 0.02). Conclusions Reducing the preprandial bolus insulin by 50% effectively attenuates exercise-induced declines in plasma glucose and substantially reduces hypoglycemia risk, particularly during intermittent high-intensity exercise. These results emphasize the clinical relevance of personalized insulin adjustments to enhance metabolic safety during exercise in individuals with T1D.

Introduction Obesity is increasingly recognized as a multifactorial disease influenced by environmental exposures, including endocrine-disrupting chemicals (EDCs). These substances interfere with hormonal signaling and may contribute to adipogenesis and metabolic dysfunction. Methods This narrative mini-review drew on epidemiological, experimental, and clinical research and examined the most recent literature on the role of EDCs in adipogenesis. It focuses on the mechanisms of action. Results Studies report that a wide variety of EDCs affect adipogenic differentiation through pathways mediated by nuclear receptors (PPARγ/RXR) and through broader endocrine disruptions involving estrogen-, glucocorticoid-, and thyroid-related pathways. Adiposity, including body weight, BMI, and abdominal obesity, is associated with chemical exposure, according to clinical data from human studies. Since they may differ based on the EDCs, the timing of exposure, and sex, the strength and consistency of the effects are still not entirely understood. Conclusions One important environmental factor in the development of obesity is EDCs. Public health interventions should prioritize identifying and regulating them.

Background With expanding applications of artificial intelligence (AI) within the research pipeline of endocrinology, it is essential that journals uphold explicit AI usage policies that maintain the rigor and integrity of published research. In this review, we aim to evaluate current AI policies of leading endocrinology journals to assess the current landscape of research and the implications of its progression. Methods We conducted a cross-sectional review of the top endocrinology journals using the SCImago Journal Ranking (SJR) database. From November 2024 to July 2025, we reviewed AI usage guidelines from publicly available Instructions for Authors, including authorship, manuscript writing, and content/image generation. We also assessed whether journals endorsed AI-specific reporting guidelines (e.g., CONSORT-AI, SPIRIT-AI). Data were extracted independently and in duplicate using a standardized form. Reproducibility was supported through protocol registration on Open Science Framework. Results Of the top 100 endocrinology journals, 84.0% (84/100) mentioned AI in their Instructions for Authors and 79.0% (79/100) required disclosure of AI use during submission. Although no journals (0/100) permitted AI tools for authorship, 64.0% (64/100) allowed its use in manuscript writing, 22.0% (22/100) for content generation, and 50.0% (50/100) for image generation. Despite these guidelines, only one (1.0%; 1/100) journal required a specific reporting guideline, and very few endorsed AI statements by the IMCJE (9/100), COPE (12/100), or WAME (0/100). No statistically significant correlations were identified between AI usage policies and SJR or impact factor. Conclusion Many leading endocrinology journals have addressed AI use; however, their policies remain incomprehensive. It is critical that publishers and their journals establish explicit guidelines regarding the use of AI tools to promote transparent, reproducible, and reliable research.

Background Achieving rapid glycemic stabilization is a critical goal in the inpatient management of type 2 diabetes mellitus(T2DM). This study aimed to develop and validate a nomogram incorporating the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and key clinical parameters to predict the time to glycemic stability in hospitalized T2DM patients. Methods We conducted a retrospective analysis of 356 hospitalized T2DM patients. Baseline demographic, clinical, and laboratory data, including the HALP score, were collected. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent predictors for the time to glycemic stability. The model’s discriminative ability was assessed using the concordance index, and its calibration was evaluated with calibration curves. Decision curve analysis (DCA) was used to estimate clinical utility. Results Multivariate Cox regression analysis identified older age, lower hemoglobin level, higher hemoglobin A1c (HbA1c), and a lower HALP score as independent risk factors associated with a longer time to glycemic stability. These four variables were integrated into a prognostic nomogram, which demonstrated good predictive accuracy, with a C-index of 0.81(95% CI:0.78 – 0.84) in the training cohort. The calibration curves showed satisfactory agreement between predicted and observed probabilities. Decision curve analysis (DCA) indicated favorable clinical net benefit across a reasonable range of threshold probabilities. Conclusions We developed and validated a practical nomogram that effectively predicts the time to glycemic stability in hospitalized T2DM patients, that may assist clinicians in early identification of patients at risk for delayed stabilization, thereby facilitating personalized management strategies and optimizing inpatient diabetes care.

Immune checkpoint inhibitors (ICIs) significantly improve prognosis and survival outcomes in cancer patients by enhancing immune function, thereby providing new therapeutic hope for cancer patients. However, with the widespread clinical application of ICIs, an increasing number of immune-related adverse events (irAEs) have been reported. Immune checkpoint inhibitor-induced type 1diabetes mellitus (ICI-T1DM) is a rare but potentially life-threatening irAE, usually presenting as acute onset and easily progressing to diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS), which poses a serious threat to patients’ safety. This study reports a case of DKA in an 81-year-old female patient diagnosed with cervical squamous cell carcinoma without history of diabetes mellitus, which developed after multiple cycles of Cadonilimab. The patient’s blood glucose levels were effectively controlled via insulin therapy and fluid resuscitation, and a definitive diagnosis of ICI-T1DM was confirmed. Taking this case as a starting point, this article reviews the epidemiology, clinical characteristics, pathogenesis, and clinical management strategies of ICI-T1DM, aiming to enhance clinicians’ awareness of ICI-T1DM, especially the endocrine toxicity of dual-target ICIs such as cadonilimab, and provide practical reference for ensuring the safety of ICI therapy in cancer patients.

Background Hemoglobin A1c (HbA1c) is a critical biomarker used for the diagnosis and management of diabetes. However, nonglycemic genetic variations may affect the accuracy of HbA1c measurements. Methods We presented a clinical evaluation of a type 2 diabetic patient with an SLC4A1 (solute carrier family 4 member 1) gene mutation, characterized by high blood glucose and low HbA1c, and estimated the carrier frequency of SLC4A1 variants in Chinese population. Results A 56-year-old patient with type 2 diabetes presented with a low HbA1c level, an elevated glycated albumin percentage (GA), normal hemoglobin and albumin levels, hemolysis, and increased red blood cell osmotic fragility. Exome sequencing revealed a heterozygous mutation in SLC4A1 gene (c.1239_1241del), which is associated with hereditary spherocytosis. Further research indicates that around 0.756% of individuals in China carry pathogenic or likely pathogenic SLC4A1 variants. Conclusions We report the SLC4A1 c.1239_1241del variant, which perturbs HbA1c via nonglycemic mechanisms, likely through a reduction in the erythrocyte lifespan, and similar variants may not be rare in Chinese population.