Frontiers in Endocrinology最新文献

Introduction: Studies have shown a strong correlation between the cardiometabolic index (CMI) and health issues such as diabetes, atherosclerosis, and decreased renal function. Nevertheless, the correlation between CMI and diabetic kidney disease (DKD) remains ambiguous. The objective of this study is to evaluate the correlation between CMI and DKD in patients with diabetes in the United States.

Methods: The study involved individuals who were part of the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2018. A multivariable logistic regression analysis was employed for investigating the correlation between CMI and DKD. The study employed Generalized Additive Models (GAM) and smooth curve fitting methods for investigating the nonlinear relationship between CMI and DKD. Two-stage regression analysis was applied for investigating threshold effects in the connection between CMI and DKD. In addition, subgroup analysis and interaction tests were also carried out.

Results: This analysis included a total of 6,540 adults with diabetes. After adjusting for variables including age, sex, race, education level, smoking status, household income and poverty rate, body mass index, hypertension status, aspartate aminotransferase, alanine aminotransferase, serum albumin, and serum globulin, we discovered a significant connection between CMI levels and the risk of DKD (OR=1.11, 95% CI: 1.05, 1.17, p<0.0001). Individuals with varying smoking statuses showed variations in this connection according to subgroup analysis and interaction tests (p for interaction=0.0216). Conversely, this correlation appeared similar across different genders, ages, races, BMI categories, hypertension statuses, and insulin usage among people with diabetes (all p for interaction >0.05). A nonlinear relationship existed between CMI and DKD, with threshold analysis indicating a turning point at CMI=1.7. A positive correlation was observed between CMI levels in people with diabetes and the risk of DKD when CMI exceeded 1.7.

Conclusion: The risk of DKD was significantly positively correlated with the CMI levels of people with diabetes. Further larger prospective studies are required to confirm our results.

Background: Triglyceride-glucose (TyG) index has been found to be associated with female reproductive disorders, but its relationship with the risk of endometriosis is unknown. Therefore, the aim of this study was to investigate this relationship.

Methods: We performed a two-sample mendelian randomization(MR) analysis to examine the causal effect of TyG index on endometriosis, and inverse variance weighting(IVW) was the main method of analysis. Then, we selected 1484 participants with endometriosis from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Weighted multivariable-adjusted logistic regression and smoothed curve analysis were used to evaluate the correlation between the TyG index and endometriosis.

Results: The results of MR analysis confirmed that higher TyG index was causally associated with the risk of endometriosis (OR=1.27, 95%CI: 1.05-1.54, P=0.01). In the cross-sectional study, subjects in the highest quartile of TyG index had the highest risk of incident endometriosis after adjusting for covariates(OR = 2.41, 95% CI:1.31-4.44, P for trend <0.01). The smoothed curve analysis also revealed a positive linear correlation between TyG index and endometriosis.

Conclusion: Our study confirms that a higher TyG index is associated with an increased risk of endometriosis by MR analysis and cross-sectional study. These findings suggested that TyG index could serve as a biomarker in identifying individuals who may be at a higher risk for developing endometriosis. Further research is needed to explore the potential clinical implications of these findings and to elucidate the underlying mechanisms behind this observed relationship.

The article provides an overview of the current understanding of the interplay between metabolic pathways and immune function in the context of triple-negative breast cancer (TNBC). It highlights recent advancements in single-cell and spatial transcriptomics technologies, which have revolutionized the analysis of tumor heterogeneity and the immune microenvironment in TNBC. The review emphasizes the crucial role of metabolic reprogramming in modulating immune cell function, discussing how specific metabolic pathways, such as glycolysis, lipid metabolism, and amino acid metabolism, can directly impact the activity and phenotypes of various immune cell populations within the TNBC tumor microenvironment. Furthermore, the article explores the implications of these metabolic-immune interactions for the efficacy of immune checkpoint inhibitor (ICI) therapies in TNBC, suggesting that strategies targeting metabolic pathways may enhance the responsiveness to ICI treatments. Finally, the review outlines future directions and the potential for combination therapies that integrate metabolic modulation with immunotherapeutic approaches, offering promising avenues for improving clinical outcomes for TNBC patients.

Introduction: Polycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D). Obesity and PCOS exacerbate each other, with central obesity driving metabolic changes. Mitochondrial dysfunction, characterized by oxidative stress and reduced antioxidant capacity, plays a key role in PCOS pathology.

Methods: In our study, we investigated 81 women with PCOS, and 57 control women aged 16 to 46 years old. Relative mitochondrial DNA (mtDNA) content and its oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method real-time PCR.

Results: Our findings showed that patients with PCOS had decreased mtDNA content and increased oxidation damage. Stratifying these patients by metabolic profile, revealed a progressive decline in mtDNA content from the normal-weight control group to the MHO-PCOS and MUO-PCOS groups, suggesting that lower mtDNA content is linked to obesity and worse metabolic profile. However, mtDNA oxidation levels did not differ significantly among these groups. Additionally, the decline in mtDNA content and the increase in oxidation levels between controls and patients with PCOS lost significance when these relationships were adjusted for the HOMA index.

Discussion: This finding suggests that IR could be the main factor contributing to mitochondrial dysfunction in PCOS. Maintaining optimal mtDNA copies are crucial for mitochondrial and cell function, suggesting potential therapeutic targets for PCOS-associated metabolic disturbances.

Background: The global prevalence of diabetes has been rising rapidly in recent years, leading to an increase in patients experiencing hyperglycemic crises like diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Patients with impaired renal function experience a delay in insulin clearance, complicating the adjustment of insulin dosing and elevating hypoglycemia risk. Accordingly, this study aims to evaluate the impact of renal function on the safety and efficacy of insulin use in patients with isolated DKA or combined DKA/HHS.

Methods: A retrospective observational study was conducted at King Abdulaziz Medical City, Saudi Arabia, from January 2016 to December 2021. Eligible patients were ≥18 years, had a confirmed diagnosis of isolated DKA or combined DKA/HHS, presented with an anion gap (AG) of ≥ 16 mmol/L, and received insulin either via continuous infusion or as bolus doses. Patients were categorized into normal kidney function and patients with chronic kidney disease (CKD). The primary outcome was to determine the difference in time to close the AG between the two groups. Statistical analyses were performed using SAS® software.

Results: Out of 319 screened patients, 183 patients met the inclusion criteria. The patients were divided into normal kidney function (43.2%) and CKD (56.8%) groups. The average eGFR for patients with normal kidney function was 93.7 ± 32.5 mL/min/1.73m² compared to 33.4 ± 14.3 mL/min/1.73m² for patients with CKD. The time to close AG was similar between patients in the normal kidney function and CKD groups (22.6 ± 16.0 hours vs. 24.5 ± 17.5 hours, p=0.4475). However, the patients' length of stay in hospital (3.4 ± 2.5 days vs. 5.2 ± 4.0 days; p=0.0004) and ICU (2.5 ± 1.8 days vs. 4.0 ± 2.8 days; p=0.0453) were both significantly longer for patients with CKD. Hypoglycemic events were low in our study with only four documented cases among patients with CKD.

Conclusion: This study provides insights into DKA management and outcomes in patients with normal and impaired renal function. The time required to close AG was comparable between the two groups. Larger, multi-center studies are needed to validate these findings and explore additional factors that may impact the management of DKA in patients with CKD.

Cardiac hypertrophy is an adaptive response to pressure or volume overload such as hypertension and ischemic heart diseases. Sustained cardiac hypertrophy eventually leads to heart failure. The pathophysiological alterations of hypertrophy are complex, involving both cellular and molecular systems. Understanding the molecular events that inhibit or repress cardiac hypertrophy may help identify novel therapeutic strategies. Increasing evidence has indicated that extracellular vesicle (EV)-derived microRNAs (miRNAs) play a significant role in the development and progression of cardiac hypertrophy. In this review, we briefly review recent advancements in EV research, especially on biogenesis, cargoes and its role in cardiac hypertrophy. We then describe the latest findings regarding EV-derived miRNAs, highlighting their functions and regulatory mechanisms in cardiac hypertrophy. Finally, the potential role of EV-derived miRNAs as targets in the diagnosis and treatment of cardiac hypertrophy will be discussed.

Background: Continuous glucose monitoring (CGM) improves glycemic control and quality of life. Data on glycemic indices and fear of hypoglycemia (FoH) in newly diagnosed T1DM patients are limited.

Aim: To assess the impact of initiating intermittently scanned CGM (isCGM) within 1-6 months of diagnosis on glycemic control and FoH in adults with T1DM.

Subjects and methods: After wearing a blinded sensor for 14 days, participants were randomized (1:1) to either isCGM (intervention) or self-monitoring blood glucose (SMBG) with glucometers and blinded CGM (control). Primary outcomes were changes in time below 70 mg/dl (TB70) and FoH, assessed in the Hypoglycemia Fear Survey (HFS). Main secondary outcomes included changes in mean glucose and time in range (TIR) from baseline to 4 weeks after randomization.

Results: The full analysis set included 23 patients (12 from the intervention group and 11 from the control group), aged 25.6 ± 5.1 years (14 men, 9 women). All participants were on multiple daily insulin injections. TB70 changed from 2.42% to 2.25% in the intervention, and from 2.81% to 1.82% in the control group, and the between-therapy difference of 0.83% was insignificant. No difference between intervention and control groups in change in HFS-worry and HFS-behavior subscales between baseline and after 4 weeks was found (-1.6 ± 3.2 and 1.0 ± 2.2, respectively). The mean glucose levels changed from 7.03 mmol/l to 6.73 mmol/l and from 7.07 mmol/l to 7.43 mmol/l, in the intervention and control groups, respectively, which resulted in a between-therapy significant glucose difference of -0.66 mmol/l. The mean TIR changed from 88.0% to 90.0% in the intervention group and from 85.2 to 84.1% in the control group-the between-therapy difference was insignificant (3,1%). The study ended early due to CGM reimbursement policy changes, after which most patients eligible for the study could have isCGM reimbursed.

Conclusions: In newly diagnosed T1DM adults, TIR is high and hypoglycemia risk is low. The study group was small; however, the data suggest that the use of isCGM soon after T1DM diagnosis could result in mean glucose decrease, but not in change in TB70 and FoH.

Objective: Recent studies have underscored the metabolic and cardiovascular regulatory capacity of perirenal adipose tissue (PAT), implicating its potential involvement in the pathogenesis of left ventricular hypertrophy (LVH). This investigation aims to assess the relationship between increased PAT mass and LVH, while also examining the potential mediating role of insulin resistance in this relationship among individuals with type 2 diabetes mellitus (T2DM).

Method: 1112 individuals with T2DM were prospectively recruited for this study. Perirenal fat thickness (PrFT), measured using unenhanced abdominal CT, served as a measure of PAT mass. The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) was computed to assess insulin resistance. LVH was identified as left ventricular mass index (LVMI) >115 g/m² in men or LVMI >95 g/m² in women. The correlations of LVH risk with PrFT and TG/HDL-c were analyzed by weighted binomial logistic regression and restricted cubic splines (RCS) analyses. Furthermore, the mediating role of TG/HDL-c in this relationship was explored using the adjusted mediation analysis.

Results: Participants in the LVH group displayed significantly higher PrFT and TG/HDL-c than the non-LVH group (P < 0.001). Adjusting for confounding factors, the LVMI demonstrated a positive correlation with PrFT (β=0.262, P<0.001) and TG/HDL-c (β=0.206, P<0.001). PrFT and TG/HDL-c emerged as independent variables for LVH, with odds ratios of 1.33 (95%CI:1.24-1.43, P<0.001) and 1.20 (95%CI:1.05-1.36, P=0.006), respectively. Each standard deviation increases in PrFT and TG/HDL-c conferred an additional 240% (P<0.001) and 41% (P=0.006) risk for LVH. A linear correlation of LVH risk with PrFT and TG/HDL-c was observed from RCS analysis (P for nonlinear and overall< 0.001). Moreover, TG/HDL-c mediated 13.4% of the association between PrFT and LVMI, and 8.5% between PrFT and LVH.

Conclusion: Increased PAT accumulation contributes to an independent variable for LVH, with insulin resistance acting as a mediating variable in this relationship.

Recombinant human IGF-1 is used to treat severe primary IGF-1 deficiency, but this treatment requires twice-daily injection, often does not fully correct the growth deficit, and has important off-target effects. We therefore sought to target IGF-1 to growth plate cartilage by generating fusion proteins combining IGF-1 with single-chain human antibody fragments that target matrilin-3, a cartilage matrix protein. We previously showed that this cartilage-targeting IGF-1 fusion protein (CV1574-1) promoted growth plate function in a GH-deficient (lit) mouse model. Here, we studied CV1574-1 in a second mouse model, C57BL/6 wild-type mice treated with pegvisomant to induce GH resistance. In this model, once-daily injections of CV1574-1 for 5 days partially restored the pegvisomant-induced decrease in growth plate height without increasing kidney cell proliferation. Furthermore, we found that subcutaneous CV1574-1 showed significantly reduced hypoglycemic effect compared to injection of IGF-1 itself. Lastly, to gain mechanistic insights into the role of matrilin-3 targeting, we assessed the ability of CV1574-1 to activate AKT signaling in vitro and found that CV1574-1 caused a prolonged increase in AKT signaling compared to IGF-1 and that this effect was dependent on matrilin-3. Taken together, our findings provide further evidence that cartilage-targeted therapy could provide new pharmacological approaches for the treatment of childhood growth disorders, such as GH-insensitivity syndrome.

Oxidative stress (OS) is established as a key factor in the etiology of both male and female infertility, arising from an imbalance between reactive oxygen species (ROS) production and the endogenous antioxidant (AOX) defenses. In men, OS adversely affects sperm function by inducing DNA damage, reducing motility, significantly impairing sperm vitality through plasma membrane peroxidation and loss of membrane integrity, and ultimately compromising overall sperm quality. In women, OS is implicated in various reproductive disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure, leading to diminished oocyte quality, disrupted folliculogenesis, and poorer reproductive outcomes. Antioxidant therapy represents a promising intervention to mitigate the harmful effects of ROS on reproductive health in additions to its easy accessibility, safety, and low cost. Despite several findings suggesting improvements in fertility potential with AOX therapy, the data remains inconclusive regarding optimal dosage and combination, duration of treatment, and the specific patient populations most likely to benefit. In this review, we discuss the role of AOXs in the management of infertile couples, focusing on their biological mechanisms, potential adverse effects, therapeutic efficacy, and clinical applications in improving reproductive outcomes in both natural conception and medically assisted reproduction. Additionally, we highlight the current practice patterns and recommendations for AOX supplementation during the course of infertility treatment. Further, we provide an overview on the limitations of the current research on the topic and insights for future studies to establish standardized AOX regimens and to assess their long-term impact on key outcomes such as live birth rates and miscarriage rates.