Frontiers in Endocrinology最新文献

Background: The monocyte-to-lymphocyte ratio (MLR) has emerged as a novel marker of inflammation. Nevertheless, its potential utility in predicting the development of left ventricular aneurysm (LVA) remains unexplored. This study aims to investigate the association between MLR and the risk of LVA in patients presenting with acute ST segment elevation myocardial infarction (STEMI).

Methods: A total of 551 patients were enrolled in the first cohort, and 471 patients were included in the validation cohort. To evaluate the predictive value of MLR for LVA, multivariable logistic regression analysis, restricted cubic splines (RCS) analysis, and receiver operating characteristic (ROC) analysis were employed.

Results: The prevalence of LVA was 14.5% in the first cohort and 13.6% in the validation cohort. The multivariable logistic regression analysis revealed that individuals in the highest quartile of MLR (Q4) exhibited a significantly increased risk of LVA formation compared to those in the lowest quartile (Q1) in both cohorts (first cohort: OR = 3.07, 95% CI = 1.33-7.08, P = 0.009; validation cohort: OR = 3.55, 95% CI = 1.34-9.42, P = 0.011). The RCS analysis identified a positively nonlinear association in the first cohort and a positively linear association in the validation cohort between MLR and the risk of LVA (overall P < 0.05). Furthermore, the discriminative ability of MLR for LVA is 0.69 in the first cohort and 0.71 in the validation cohort, exceeding that of both monocyte and lymphocyte alone. The subgroup analyses further substantiated the robustness of our findings.

Conclusion: An elevated MLR was independently linked to an increased risk of LVA development in patients with STEMI who received primary PCI. This readily available inflammatory index may offer supplementary prognostic information and could be considered for inclusion in future risk stratification models.

Background: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to high cardiovascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors can offer glycemic and cardiorenal benefits. Most agents are available in low and high doses, with the assumption that higher doses improve glycemic control. However, previous evidence shows only marginal hemoglobin A1c (HbA1c) reduction (≈0.08-0.18%) with high doses, raising uncertainty about their clinical necessity. Patient factors such as baseline HbA1c and renal function influence SGLT2 efficacy, but whether these factors modify dose response remains unclear. This study evaluates dose-dependent effects across HbA1c and renal function strata.

Objective: To assess the glycemic impact of high- versus low-dose SGLT2 inhibitors in T2DM, stratified by HbA1c and renal function.

Methods: This analysis followed PRISMA guidelines (PROSPERO ID: CRD42024605351). PubMed, the Cochrane Library, and EMBASE were systematically searched for randomized controlled trials involving SGLT2 inhibitors in adults with T2DM through November 24, 2024. The primary outcome was change in glycated hemoglobin, stratified by hemoglobin A1c (HbA1c) and glomerular filtration rate (GFR) levels. Subgroup analyses were performed based on different SGLT2 inhibitors and dosages.

Results: A total of 23 studies were included for the meta-analysis. Seventeen studies (n = 7,021) were stratified by HbA1c, and eight (n = 7,998) by GFR. Overall, high-dose SGLT2 inhibitors showed a slightly better glycemic control than low-dose SGLT2 inhibitors, with an additional 0.08% (95%CI: -0.12, -0.04) reduction in HbA1c levels. High-dose vs. low-dose SGLT2 inhibitors showed a 0.06%-0.16% further HbA1c reduction across varying glycemia levels (with HbA1c under or over 8%, 8.5%, 9%) and a change in HbA1c levels ranging from -0.07% to 0.04% across varying GFR levels (with GFR under or over 45, 60, 90 ml/min/1.73m²).

Conclusion: Dose escalation had minimal effect on HbA1c across glycemic and renal strata; higher doses of SGLT2 inhibitors offer limited additional benefit for glycemic control in poorly controlled T2DM.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024605351.

Objective: Prolactin (PRL) is increasingly recognized as a pleiotropic hormone with potent immunoregulatory properties; however, its involvement in systemic inflammation among diabetic kidney disease (DKD) patients has not been defined. This study aimed to investigate the potential association between serum PRL levels and micro-inflammation in patients with DKD.

Methods: In this cross-sectional investigation, 994 patients with type 2 diabetes mellitus (T2DM)-associated DKD were enrolled. Multivariable linear mixed-effects models were used to quantify the relationship between serum PRL and the systemic immune-inflammation index (SII) and other clinical parameters. Restricted cubic spline (RCS) analyses were fitted to test for non-linearity and stratified and sensitivity analyses were performed to assess robustness.

Results: The median serum PRL level was 344.40 mIU/L (interquartile range: 258.80-463.10). After multivariable adjustment, serum PRL were positively associated with white blood cell count, neutrophil count, serum ferritin, serum phosphorus and intact parathyroid hormone (iPTH) levels, and inversely associated with serum albumin. For every 100 mIU/L increase in serum PRL, the SII increased by an average of 7.10 units (95% CI: 3.13 to 11.07; p = 5.12 × 10^-4). Stratified and sensitivity analyses confirmed the robustness of this association. RCS analysis revealed a significant nonlinear relationship between serum PRL and SII (p for nonlinearity = 0.002), with an inflection point at 282.85 mIU/L. PRL levels above this inflection point showed a significant positive association with SII, whereas levels below it showed a negative association.

Conclusion: In patients with DKD, serum PRL exhibits an independent, nonlinear association with SII, characterized by a threshold around 282.85 mIU/L. This finding suggests that PRL may be linked to the dysregulated immune-inflammation axis in DKD, warranting further mechanistic and longitudinal investigation.

Introduction: Increased androgen production in 46,XX individuals with congenital adrenal hyperplasia leads to a variable degree of external genital virilization, often complicating the decision regarding sex assignment after birth.

Methods: In this single tertiary center retrospective study, we analyzed individuals with 46,XX karyotype and 21-hydroxylase deficiency with Prader score V or EMS 8-9, who were assigned and reared as male in the last 40 years. In parallel, we conducted a comprehensive review of published case reports on 46,XX male CAH patients to gain insight into their gender identity outcomes, surgical interventions, and quality of life.

Results: We identified four severely virilized 46,XX CAH patients, who were assigned and reared as male and have maintained a stable male gender identity. In addition, we found 63 similar published cases in the literature between 1963 and 2025. Outcome data were available in 50 cases. Among them, 43/50 patients were satisfied with male gender identity, although 3/43 underwent male to female and back to male reassignment.

Conclusion: Our experience with four patients aligns with several published case reports showing that 46,XX CAH infants with severe genital virilization reared as male may develop and maintain a stable male gender identity throughout life. However, if male sex assignment is chosen for a 46,XX child, parents should be counseled about fertility implications, future surgical needs, potential height-related concerns and the possibility of testosterone treatment. Nevertheless, individualized care, shared decision-making, parental involvement and family support appear to be essential for a positive outcome.

Objectives: To evaluate the predictive value of surrogate indices of insulin resistance (IR)- specifically, the triglyceride-glucose (TyG) index, the triglyceride glucose-body mass (TyG-BMI) index, and the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) for metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM).

Methods: A single-center, retrospective study was conducted involving 2409 T2DM patients. Based on the presence of MetS, participants were divided into a T2DM-MetS group (n=1,787) and a T2DM-only group (n=622). Logistic regression was used to analyze the influencing factors for T2DM complicated with MetS, and to compare the predictive value of the TyG index, the TyG-BMI index, and the TG/HDL-C ratio. A nomogram prediction model was constructed. The model's discriminative ability, clinical utility, and calibration were evaluated using the receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and a calibration curve, respectively.

Results: The multivariate logistic regression analysis model revealed that Sex, Wasit-to-hip ratio (WHR), fasting C-Peptide (FCP), 2-hour C-Peptide (2hCP), the TyG index, the TyG-BMI index, and the TG/HDL-C ratio were risk factors for T2DM complicated with MetS. The area under the curve (AUC) for the TyG index, the TyG-BMI index, and the TG/HDL-C ratio in predicting T2DM complicated with MetS were 0.809, 0.807, and 0.915, respectively. The prediction model was constructed using the TG/HDL-C ratio, Sex, WHR, and FCP. The model demonstrated that the C-index for predicting the presence of MetS in T2DM patients was 0.922 (95% CI: 0.909, 0.936). The DCA showed a maximum net benefit rate of 0.742.

Conclusions: The surrogate indices for IR (the TyG index, the TyG-BMI index, and the TG/HDL-C ratio) were risk factors for T2DM complicated with MetS, among which the TG/HDL-C ratio was the optimal predictor. The nomogram model constructed based on the TG/HDL-C ratio, Sex, WHR, and FCP demonstrated good predictive performance for T2DM complicated with MetS. This model shows good calibration and practicality, providing a valuable reference to aid in early identification and preventive strategies in clinical practice.

Objective: This network meta-analysis aimed to compare and rank the efficacy and safety of acupuncture-related therapies (ARTs) for polycystic ovary syndrome (PCOS) in improving insulin resistance (IR), reproductive endocrine outcomes, and ovarian morphology.

Methods: Randomized controlled trials (RCTs) in Chinese and English were retrieved up to September 2025 from eight databases (the Cochrane Library, Web of Science, PubMed, Embase, VIP, CNKI, Wanfang, and CBM). Eligible participants were women with PCOS diagnosed using established international or Chinese criteria. Interventions compared ARTs (e.g., acupuncture, moxibustion, electroacupuncture) versus conventional medication and/or placebo. The primary outcome was homeostatic model assessment of IR (HOMA-IR). Secondary outcomes included fasting insulin (FINS), fasting blood glucose (FBG), body mass index (BMI), waist-to-hip ratio (WHR), testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, antral follicle count (AFC), and ovarian volume (OV). Risk of bias was assessed using Review Manager 5.3, and network meta-analysis with surface under the cumulative ranking curve (SUCRA) rankings was conducted in Stata 17.0. All outcomes were summarized as mean differences (MDs) with 95% confidence intervals (CIs).

Results: 53 RCTs involving 4,406 participants and 12 ART regimens (including two combined regimens) were included. Acupoint injection therapy (AIT) and acupuncture plus moxibustion (Acu + Moxi) significantly reduced HOMA-IR (MD = 2.20, 95% CI 0.44-3.96; MD = 1.06, 95% CI 0.28-1.84). AIT, catgut implantation at acupoint (CIAA), and Acu reduced FINS (MD = 7.30, 95% CI 0.83-13.77; MD = 3.11, 95% CI 1.97-4.25; MD = 2.97, 95% CI 1.87-4.06). Acu + Moxi reduced BMI (MD = 5.80, 95% CI 3.38-8.22), and electroacupuncture (EA) reduced WHR (MD = 0.06, 95% CI 0.02-0.09). Laser acupuncture (LA) reduced T and LH (MD = 0.59, 95% CI 0.33-0.85; MD = 3.00, 95% CI 0.47-5.53). For ovarian morphology, warm needle therapy (WNT) and Acu reduced AFC (MD = 4.08, 95% CI 0.63-7.53; MD = 3.06, 95% CI 1.07-5.05), and Acu reduced ovarian volume (OV) (MD = 2.38, 95% CI 0.67-4.08). Overall, Acu ranked among the top interventions across multiple outcomes. Most reported adverse events were non-serious and transient. Adverse-event reporting was limited across trials.

Conclusion: ARTs may be safe and effective complementary therapies for improving IR, reproductive endocrine outcomes, and ovarian morphology in women with PCOS.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251151249, identifier CRD420251151249.

Eruptive xanthoma (EX) is a rare but clinically important dermatologic manifestation of severe hypertriglyceridemia and often serves as a cutaneous indicator of profound disturbances in glucose metabolism. Here, we describe a 27-year-old man who presented with numerous yellowish papules that clustered into lobulated, cauliflower-like plaques on the trunk and limbs, serving as the first clinical indication of underlying metabolic dysregulation. Laboratory investigations revealed extreme hypertriglyceridemia (60.45 mmol/L) and newly diagnosed diabetes mellitus (HbA1c 14.1%). Skin biopsy demonstrated foamy histiocytes and Touton giant cells in the dermis. The patient received combination therapy with fenofibrate (200 mg/day), intensive insulin therapy, and a low-fat diabetic diet, leading to rapid normalization of triglyceride levels from 60.45 mmol/L to 2.47 mmol/L by Day 32. The cutaneous lesions flattened and progressively regressed in parallel with metabolic improvement, leaving only faint post-inflammatory hyperpigmentation at the final evaluation. This case emphasizes that uncommon lobulated morphology may serve as an early visual clue of eruptive xanthomas, reinforcing the diagnostic value of cutaneous signs as metabolic sentinels and highlighting that early dual-target treatment can prevent life-threatening complications.

Objective: To investigate the effects of digital health interventions (DHIs) for improving anthropometric and healthy behavior in women with polycystic ovarian syndrome (PCOS).

Methods: Five databases were searched from their inception to April 2025 with no date restrictions. Standardized mean differences (SMDs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models. The certainty of the evidence was assessed using the GRADE approach.

Results: Ten trials with 930 participants were included. In short-term (≤3 months), DHIs yielded significant reductions in BMI (MD -1.19; -1.84 to -0.55; I²=0%), waist circumference (MD -2.14; -3.11 to -1.17; I²=0%) and large improvements in total HPLP-II score (SMD 1.61; 1.20 to 2.01; I²=0%), physical activity (SMD 1.43; 1.04 to 1.83; I²=0%), health responsibility (SMD 1.02; 0.64 to 1.39; I²=0%), interpersonal relationships (SMD 0.96; 0.59 to 1.33; I²=0%), spiritual growth (SMD 1.25; 0.87 to 1.64; I²=0%) and stress management (SMD 1.17; 0.79 to 1.55; I²=0%); there was no significant change in body weight (SMD -0.04; -0.23 to 0.15; I²=0%) or HPLP-II nutrition (SMD 0.83; -0.11 to 1.78; I²=84%). In medium-term (3-6 months), DHIs continued to reduce BMI (MD -2.46; -3.04 to -1.88; I²=22%) and waist circumference (MD -4.65; -6.70 to -2.60; I²=0%), and yielded significant improvements in depressive symptoms (SMD -0.85; -1.17 to -0.53; I²=17%) and anxiety (SMD -0.95; -1.33 to -0.56; I²=42%).

Conclusion: Digital health interventions confer significant short- and medium-term improvements in anthropometric and healthy behavior measures among women with PCOS.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251030598.

Aim: To assess the efficacy of Sodium-glucose cotransporter inhibitors (SGLTis) in the primary prevention (PP) of chronic kidney disease (CKD) among patients with type 2 diabetes (T2D).

Method: Literature was retrieved from MEDLINE, Embase, and Cochrane databases up to January 1, 2025. Eligible studies included randomized controlled trials (RCTs) or their subgroups and observational studies involving T2D patients without CKD treated with SGLTis for ≥ 1 year, focusing on CKD-related composite outcomes. Seven articles meeting inclusion criteria were included. The hazard ratio (RR) was calculated, and the degree of heterogeneity was assessed. Subsequently, 95% confidence intervals (95% CI) were computed accordingly.

Result: In RCTs, 15,228 eligible participants received SGLTis and 12,736 received placebo. Meta-analysis using random-effects models showed that SGLTis reduced CKD-related composite outcomes by 53% (RR 0.47, 95% CI 0.39, 0.57; P < 0.0001) with low heterogeneity (I² = 6%). Observational data also indicated a lower CKD incidence (0.6-0.7%) with SGLTis versus other glucose-lowering therapies in individuals with CKD PP.

Conclusions: SGLTis significantly lower CKD incidence in T2D patients without baseline CKD. Further RCTs are necessary to validate our conclusions.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251168634.