Frontiers in Endocrinology最新文献

Background: Albuminuria is a recognized marker of renal injury in diabetic kidney disease (DKD), and growing evidence suggests it may also drive systemic inflammation and atherosclerosis. However, mechanisms linking albuminuria to vascular disease remain unclear.

Methods: We conducted a cross-sectional study including 362 subjects with type 2 diabetes and moderate chronic kidney disease (CKD) to evaluate the associations between albuminuria, circulating and leukocyte inflammatory markers, and measures of subclinical atherosclerosis (SA). SA was defined by carotid intima-media thickness (CIMT) ≥0.9 mm or ankle-brachial index (ABI) <0.9. Serum levels of hs-CRP, IL6, IL1β, IL10, and TNFα and gene expression in peripheral blood leukocyte cells for IL6, IL1β, TNF, IL10, TLR2, TLR4, CCL2, NFκB, and CD36 were measured.

Results: SA was present in 46% of patients. UACR correlated directly with CIMT (r=0.32, p<0.001) and inversely with ABI (r=-0.29, p<0.01). Higher UACR was associated with increased circulating IL6 and IL1β, and elevated expression of TNF, CD36, and TLR2 in leukocytes. In multivariable analysis, serum IL6and IL1β, and leukocyte IL6 and TLR2 were independently associated with SA. Mediation analysis showed that IL6 (serum and leukocyte expression) accounted for approximately 20% of the UACR-SA association, serum IL1β mediated 17%, and leukocyte TLR2 mediated 7%.

Conclusions: Albuminuria was positively associated with heightened systemic and cellular inflammation, and several inflammatory markers were also associated with greater CIMT and the presence of early atherosclerosis. Exploratory mediation analyses suggested that inflammatory pathways may partly account for the association between albuminuria and SA, with IL6, IL1β, and TLR2 as key mediators; however, these findings should be interpreted cautiously due to the cross-sectional design.

Background: To investigate whether the severity of diabetic retinopathy (DR) and the presence of hard exudates (HEs) are associated with renal function deterioration in patients with diabetic kidney disease (DKD).

Methods: This is a retrospective cohort study including 140 patients with DKD. The outcome was the progression of DKD (an estimated glomerular filtration (eGFR) decline (%)>15%) over a 5-year follow-up period. A total of 101 patients had eGFR parameters during the follow-up. DR was categorized into nonproliferative DR (NPDR) and proliferative DR (PDR). HEs were identified via optical coherence tomography (OCT). Clinical and laboratory data were acquired from medical records. The influence of the severity of DR and the presence of HEs were assessed via Cox regression.

Results: The mean follow-up time was 34.31 (± 16.36) months. A significant difference was found in eGFR decline (%) (P = 0.024) between the absent DR, NPDR and PDR groups. eGFR decline (%) was more severe in patients with HEs than in those without HEs (P = 0.011). After adjustment for age, body mass index (BMI), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, eGFR at baseline, urine albumin creatine ratio (UACR) stage at baseline, use of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors, as well as potential confounders such as duration of Diabetic mellitus (DM), use of Renin-Angiotensin System Inhibitors (RAS) inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), Cox regression revealed that PDR (p=0.035) and NPDR (p=0.049) were independently associated with renal function deterioration. Compared with the participants in the absent DR group, participants with PDR, as well as NPDR presented a nearly threefold greater risk (adjusted HR = 2.88; 95% CI: 1.08-7.71; adjusted HR = 2.78; 95% CI: 1.004-7.70, respectively). However, the presence of HEs was not independently associated with renal function deterioration in the adjusted Cox model (P = 0.567).

Conclusions: DR severity was independently associated with the progression of DKD, whereas HEs were not. DKD patients with PDR as well as NPDR should undergo kidney function testing more frequently and receive early intervention to prevent renal function deterioration.

Background: Receptor activator of nuclear factor-κB ligand (RANKL) plays a central role in regulating osteoclast formation and bone resorption, while its inhibition by the monoclonal antibody denosumab serves as an effective antiresorptive treatment for postmenopausal osteoporosis. However, denosumab discontinuation triggers a severe rebound effect involving rapid bone mineral density (BMD) loss, accompanied by an overshooting of bone turnover markers (BTMs), and increased risk of multiple fractures. Preclinical studies investigating this rebound phenomenon after denosumab discontinuation have been limited, mainly because denosumab does not cross-react with murine RANKL. This study explores the rebound phenomenon in a transgenic mouse model of osteoporosis expressing human RANKL (TgRANKL) and evaluates the impact of sequential zoledronate therapy.

Methods: TgRANKL mice were divided into four experimental groups: vehicle control, continuous denosumab treatment, denosumab withdrawal, and sequential denosumab followed by zoledronate, including an additional follow-up phase after zoledronate discontinuation. Skeletal alterations were characterized using microCT, histomorphometric assessments, serum bone turnover markers (BTMs), and bone gene expression analyses.

Results: Denosumab therapy rescued the osteoporotic phenotype of TgRANKL mice, whereas its discontinuation resulted in a rebound bone loss accompanied by elevated bone turnover markers. Denosumab also inhibited bone marrow adipose tissue formation in TgRANKL mice, while its discontinuation led to moderate reformation of marrow adiposity. Sequential administration of zoledronate effectively prevented the rebound bone loss response. However, discontinued therapy after denosumab-zoledronate sequence, showed that the protective effects of zoledronate were not persistent.

Conclusions: Our findings establish TgRANKL mice as a unique osteoporotic model for investigating the mechanisms driving denosumab rebound and testing sequential antiresorptive strategies.

Introduction: Acupuncture has been explored as a potential intervention for POR; however, high-quality evidence is limited. This multicenter randomized trial evaluated the effect of acupuncture on the number of oocytes retrieved following controlled ovarian hyperstimulation (COH) in women with POR.

Methods: This multicenter, randomized, controlled study was conducted at nine tertiary hospitals in China between August 2018 and March 2023, with follow-up extended through March 2024. A total of 140 women aged ≤ 40 years, who met the Bologna criteria and were eligible for the antagonist ovulation induction protocol, were recruited and randomly assigned to either an acupuncture group or a control group. The acupuncture group received 36 acupuncture sessions prior to COH, while the control group received in vitro fertilization (IVF) only. The primary outcome was the number of oocytes retrieved. Secondary outcomes included embryological parameters, ovarian reserve markers, and clinical pregnancy and live birth rates.

Results: The intention-to-treat population included 140 participants. Following intervention, the number of oocytes retrieved did not differ significantly between the acupuncture group (median [IQR]: 2.00 [1.00-3.00]) and control group (median [IQR]: 2.00 [1.00-4.00]), median between-group difference: 0.00, 95% CI [-1.00, 0.00], p = 0.283). Among secondary outcomes, the cleavage rate was higher in the acupuncture group than in the control group (100% vs. 87.39%; between-group difference: 12.61%; 95% CI [6.64%, 18.57%]; p < 0.001). Basal follicle-stimulating hormone (FSH) levels were lower in the acupuncture group compared to the control group (median [IQR]: 9.08 [6.53-12.8] vs. 11.31 [8.23-16.53]; between-group difference: -2.40; 95% CI [-4.76, -0.37]; p = 0.019). There were no statistically significant differences between groups in clinical pregnancy rate (34.29% vs. 21.43%; p = 0.090), live birth rate (21.43% vs. 15.71%; p = 0.385) and other prespecified outcomes. Results from the per-protocol (PP) analysis were consistent with the ITT findings. No serious adverse events were observed.

Conclusions: This study did not find evidence that acupuncture significantly improves the number of oocytes retrieved in patients with POR. While it was associated with a significantly higher embryo cleavage rate and lower basal FSH levels, acupuncture did not significantly improve clinical pregnancy or live birth rates.

Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR1800017717.

Background: Diminished ovarian reserve (DOR) has emerged as a significant reproductive challenge and a broader societal concern. Most previous studies have focused on ovarian reserve markers, while limited research has examined DOR as a primary outcome, and the potential association between TORCH infections (toxoplasmosis, others, rubella, cytomegalovirus, herpes) and DOR risk remains unclear.

Methods: A matched case-control study was conducted among women aged 20-47 years who sought assisted reproductive technology at a maternity hospital in Sichuan, China, between January 2022 and August 2024. DOR was diagnosed according to the Consensus on clinical diagnosis and management of diminished ovarian reserve from China. Age-matched controls (1:1) with normal ovarian reserve were selected. Conditional logistic regression was used to identify factors associated with DOR, with multivariable models adjusting for confounders. Subgroup analyses by age and body mass index (BMI) were conducted to examine robustness and effect modification.

Results: A total of 3,751 DOR cases were matched to 3,751 controls (median age: 36 years). DOR group had significantly higher FSH, E2, and LH levels (P < 0.01), and lower AFC, AMH, PRL, and T levels (P < 0.001) compared to controls. Multivariable logistic regression showed that non-Han ethnicity (OR = 1.278, 95% CI: 1.115-1.466), manual labor (OR = 1.181, 95% CI: 1.002-1.392), obesity (OR = 1.316, 95% CI: 1.044-1.660), light menstrual flow (OR = 1.262, 95% CI: 1.111-1.435), and T. gondii infection (OR = 2.292, 95% CI: 1.683-3.122) were independently associated with DOR. In women aged 20-35 years, ≥2 pregnancies (OR = 0.712, 95% CI: 0.615-0.824), and infections with T. gondii (OR = 23.750, 95% CI: 13.330-42.316), CMV (OR = 8.189, 95% CI: 5.821-11.521), and RV (OR = 8.132, 95% CI: 5.806-11.390) were strongly associated with DOR, with no such associations observed in the 36-47 years group. Significant age interactions were detected (P < 0.05).

Conclusion: Ethnicity, obesity, menstrual flow, pregnancy history, and TORCH infections were significantly associated with DOR, with age-related effect modification observed for pregnancy history and infections. Prospective studies are needed to elucidate the underlying mechanisms, particularly the role of infections and immune response.

Objective: Copper overload has been implicated in impaired β-cell function and insulin resistance through oxidative stress and inflammatory pathways. As a major lipoprotein component involved in lipid oxidation, apolipoprotein B (apoB) may influence copper-related metabolic effects. This study aimed to examine the association between whole blood copper concentration and glycemic control in patients with type 2 diabetes mellitus (T2DM), and to assess whether apoB levels influence this association.

Methods: A total of 117 patients with T2DM (mean age 55.15 ± 10.70 years; 62.4% male) were included. Whole blood copper concentration was measured using inductively coupled plasma mass spectrometry. Associations between blood copper and glycemic indicators, including glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG), were evaluated using multivariable linear regression models. Stratified and interaction analyses were performed according to apoB and other lipid-related parameters.

Results: After adjustment for potential confounders, a significant interaction between blood copper and apoB was observed in relation to HbA1c (P for interaction< 0.001). Stratified analyses showed that higher blood copper concentration was significantly associated with higher HbA1c levels among patients with lower apoB levels below the study median, whereas no significant association was observed among those with higher apoB levels. Exploratory analyses further indicated that apoB also influenced the association between blood copper and FPG (P for interaction< 0.05), showing a consistent pattern.

Conclusion: In patients with T2DM, a significant association between blood copper concentration and glycemic control was observed among individuals with lower apoB levels, whereas no such association was found among those with higher apoB levels. These findings suggest that apoB status may influence the relationship between blood copper and glycemic control and merit further investigation in longitudinal studies.

Background: For patients with poor glycemic control of adult type 1 diabetes mellitus (T1DM), in addition to managing blood glucose levels, it is worth exploring further as an early warning indicator of blood glucose control.

Methods: 56 adults with T1DM, aged between 18 and 70 years, were included in the study. Data on body composition and laboratory indicators, including phase angle values and HbA1c levels, were collected. Statistical analysis was conducted to determine the correlation and the strength of association between the phase angle, and HbA1c levels.

Results: Pearson's correlation and linear regression models indicated a negative correlation between phase angle and HbA1c levels, even after controlling for age and weight in both males and females.

Conclusion: The results indicate a significant negative relationship between Phase angle and HbA1c levels. Beyond being a simple body composition parameter, Phase angle can be used as a clinical indicator of improved blood glucose control.

Background: Left ventricular diastolic dysfunction (LVDD) is a common complication of type 2 diabetes (T2DM), closely associated with obesity and visceral adiposity. The Body Roundness Index (BRI) is a novel anthropometric measure that may better reflect visceral fat distribution, yet its relationship with LVDD in T2DM remains unclear.

Objective: This study aims to investigate the association between BRI and LVDD risk in patients with T2DM, focusing on nonlinear relationships and potential threshold effects.

Methods: This cross-sectional study included 1,317 patients with T2DM. Multivariable logistic regression and generalized additive models (GAM) were used to assess associations, with adjustment for key confounders. Threshold effects were evaluated using a two-step recursive approach, and subgroup analyses were performed.

Results: After full adjustment, each one-unit increase in BRI was associated with a 30% higher risk of LVDD (OR: 1.30, 95% CI: 1.10-1.60, p < 0.001). A nonlinear relationship was identified with an inflection point at BRI = 8.1. Below this point, the association was stronger (OR: 1.50, 95% CI: 1.20-1.80, P < 0.001). Diabetic kidney disease significantly modified this association (P for interaction = 0.02).

Conclusion: BRI is nonlinearly associated with LVDD risk in T2DM, with a threshold effect at BRI = 8.1. The association is stronger in patients with diabetic kidney disease, suggesting that BRI could serve as a valuable marker for the stratification and prevention of LVDD in high-risk populations.