Frontiers in Endocrinology最新文献

Objective: To explore the differential gene expression in peripheral blood immune cells of individuals with type 2 diabetes mellitus (DM), comparing those with and without non-proliferative diabetic retinopathy (NPDR).

Methods: From a pool of 126 potential participants, 60 were selected for detailed analysis. This group included 12 healthy donors (HDs), 22 individuals with DM, and 26 with NPDR. We analyzed peripheral blood mononuclear cells (PBMCs) using RNA sequencing and quantitative PCR (qPCR) to pinpoint differentially expressed genes (DEGs). Western blot and flow cytometry were also employed to evaluate the protein expression of specific genes.

Results: In patients with NPDR compared to those with DM alone, MerTK-a gene implicated in inherited retinal dystrophies due to its mutations-was notably downregulated in PBMCs. Through flow cytometry, we assessed the protein levels and cellular distribution of MerTK, finding a predominant expression in monocytes and myeloid-derived suppressor cells (MDSCs), with a marked reduction in CD4+ and CD8+ T cells, as well as in natural killer T (NKT) cells. Patients with DM demonstrated a significant deviation in the PBMCs composition, particularly in B cells, CD4+ T cells, and NK cells, when compared to HDs.

Conclusions: The study indicates that MerTK expression in T cells within PBMCs could act as a viable blood biomarker for NPDR risk in patients with DM. Furthermore, the regulation of T cells by MerTK might represent a critical pathway through which DM evolves into NPDR.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.

[This corrects the article DOI: 10.3389/fendo.2024.1392418.].

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which has poor prognosis with a short median overall survival of 6-12 months and a low 5-year survival rate of approximately 3%. It is crucial to remove PanIN lesions to prevent the development of invasive PDAC, as PDAC spreads rapidly outside the pancreas. This review aims to provide the latest knowledge on PanIN risk, pathology, cellular origin, genetic susceptibility, and diagnosis, while identifying research gaps that require further investigation in this understudied area of precancerous lesions. PanINs are classified into PanIN 1, PanIN 2, and PanIN 3, with PanIN 3 having the highest likelihood of developing into invasive PDAC. Differentiating between PanIN 2 and PanIN 3 is clinically significant. Genetic alterations found in PDAC are also present in PanIN and increase with the grade of PanIN. Imaging methods alone are insufficient for distinguishing PanIN, necessitating the use of genetic and molecular tests for identification. In addition, metabolomics technologies and miRNAs are playing an increasingly important role in the field of cancer diagnosis, offering more possibilities for efficient identification of PanIN. Although detecting and stratifying the risk of PanIN poses challenges, the combined utilization of imaging, genetics, and metabolomics holds promise for improving patient survival in this field.

Background: The triglyceride-glucose (TyG) index and related indices, including the triglyceride-glucose body mass index (TyG-BMI), triglyceride-glucose waist circumference (TyG-WC), and triglyceride-glucose waist-to-height ratio (TyG-WHtR), are increasingly recognized as valuable markers of insulin resistance (IR). This study aimed to assess the associations between these TyG-related indices and kidney stones.

Methods: This cross-sectional study analyzed data from 10,824 participants obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2020. Weighted logistic regression models were employed to evaluate the associations between TyG-related indices and kidney stones, with adjustments for potential confounding factors. Subgroup analyses and smooth curve fittings were performed to further examine these associations, while receiver operating characteristic (ROC) curves were used to compare the predictive performance of each index.

Results: All TyG-related indices demonstrated significant positive associations with kidney stones when analyzed as continuous variables. The odds ratios (OR) with 95% confidence intervals (CI) were 1.0040 (1.0028, 1.0052) for TyG-BMI, 1.0015 (1.0011, 1.0020) for TyG-WC, and 1.3305 (1.2277, 1.4419) for TyG-WHtR. Similar trends were observed in subgroup and smooth curve analyses. When stratified into tertiles, higher tertiles of each TyG-related index were associated with increased odds of kidney stones. TyG-WC demonstrated the strongest predictive capability for kidney stones (AUC = 0.6158), followed closely by TyG-WHtR (AUC = 0.6156) and TyG-BMI (AUC = 0.5949), with TyG showing the lowest AUC (0.5815).

Conclusion: This study identified significant positive associations between TyG-related indices and kidney stone formation. Among these indices, TyG-WHtR exhibited the highest predictive power for identifying kidney stone risk.

Background: Amputation confers disabilities upon patients and is linked to cardiometabolic morbidity and mortality. We aimed to compare the incidence of type 2 diabetes (T2DM) between individuals following amputation with those of the general population.

Methods: We performed a population-based retrospective cohort study using the Nationwide Health Insurance Service database. A total of 21,343 individuals with amputation during 2010-2018 and their 1:3 age- and sex-matched controls was included. We conducted Cox proportional hazard analysis to calculate the risk of T2DM among individuals with amputation.

Results: During the 4.2 ± 2.5 year mean follow-up period, there were 912 incident T2DM cases (10.7 per 1,000 person-years) among individuals with amputation. Individuals with amputation had a higher risk for T2DM (adjusted hazard ratio [aHR] 1.11, 95% confidence interval [CI] 1.03-1.20) compared with matched controls. The risks were increased further when accompanied with disability; those with severe disability had a higher risk of T2DM (aHR 1.77, 95% CI 1.20-2.60) than matched controls. Individuals with proximal upper limb amputation (aHR 1.10, 95% CI 1.02-1.18) and proximal lower limb amputation (aHR 3.60, 95% CI 1.50-8.64) had a higher risk of T2DM compared with matched controls.

Conclusions: Individuals with amputation were at significantly greater risk for T2DM than the general population, particularly those with severe disability and proximal amputation. Innovative strategies that improve and support the long-term T2DM risk for severely injured individuals with proximal amputation are warranted.

Background: A novel and rapid cell-based bioassay, Turbo TSI, for measurement of thyroid-stimulating immunoglobulins (TSI) was recently reported. An assessment of the analytical performance of this TSI bioassay is described herein.

Methods: Thawed cells from Turbo TSI kits were treated with different concentrations of a World Health Organization (WHO) international standard (IS) TSI-positive serum. TSI was measured as a function of luciferase activity measured as relative light units (RLU) and converted into international units per liter (IU/L). Analytical performance studies were performed on numerous samples, over multiple days, by two users at two sites.

Results: The limit of blank, limit of detection and limit of quantitation were determined to be 0.007 IU/L, 0.014 IU/L, and 0.021 IU/L, respectively. Receiver operator characteristics (ROC) analysis determined the cut-off to be 0.0241 IU/L with an area under the curve of 0.984. The linear range was shown to be from 0.015 to 11.958 IU/L. The intra-laboratory precision was ≤15%CV. The overall reproducibility of the assay was ≤20%CV for five concentrations (0.06 to 5.16 IU/L). Interference and cross reactivity studies with a variety of substances showed that the assay was robust. The Turbo TSI bioassay demonstrated 95.2% (95% CI 83.3-98.1) positive percent agreement and 94.8% (95% CI 90.9-97.1) negative percent agreement with an FDA-cleared bioassay (Thyretain ^® TSI) using serum from 295 patients with autoimmune thyroid disease.

Conclusions: The Turbo TSI bioassay exhibits excellent analytical performance and a high level of reproducibility. The performance compared well with Thyretain ^® TSI, an FDA-cleared TSI bioassay.

Introduction: Pre-implantation testing (PGT) is often suggested by healthcare professionals (HCP) to parents of children with congenital adrenal hyperplasia (CAH) considering subsequent children. Despite this, some families choose to conceive naturally without genetic testing and intervention. The aims of this study were to explore fertility choices of couples with a child with CAH and the decision making process and perceptions behind these choices, and to explore the families' lived experiences with CAH and the couples' subsequent fertility journey. A better healthcare professional understanding of these experiences may subsequently help guide clinicians to better manage and support families of children with CAH and other autosomal recessive conditions.

Methods: All parents of current children of a tertiary service in 2020 with 21-hydroxylase deficient CAH who made an active decision regarding family planning after diagnosis of their index child were invited to participate in a semi-structured interview. Thematic analysis was performed using an inductive, semantic approach.

Results: Thirty families (34 children) were identified. Fourteen considered subsequent children and had directed genetic counselling. Eight decided to have additional children of whom seven agreed to participate. Thematic analysis identified six key domains. Psychological impact surrounding the CAH diagnosis was long-lasting, causing symptoms of trauma including depression and anxiety, and influencing a couple's choice to pursue PGT to avoid having another affected child. The perception of the index child having a mild phenotype, and fear of a more severe phenotype, often supported this decision. Conversely, lived experience of CAH and low day-to-day impact, along with a negative experience of PGT, with a greater than anticipated financial, physical, and emotional toll, led some families to subsequently consider natural conception. The role of the healthcare professional (HCP) was important in the CAH and family planning journeys. A perceived poor understanding of CAH, overstating its potential seriousness, contributed to distress. Parents reported feeling pressured to undergo PGT. Peer-support had a universally positive impact on family experience.

Discussion/conclusions: This study highlights the complex and dynamic nature of fertility decision-making, and the importance of HCP empathy and open-mindedness. Education of HCP and encouraging peer support may improve the CAH and fertility journey for families.

Introduction: Premature ovarian insufficiency (POI) is a condition characterized by ovarian dysfunction occurring before the age of 40, and its etiology is multifactorial, including genetic, immunological, infectious, environmental, and iatrogenic factors, with over half of the cases remaining unexplained. Whether the microbial communities and metabolites in follicular fluid, which is the direct microenvironment for oocyte survival, are related to POI has not been reported.

Methods: In this study, Follicular fluid samples of 26 patients with POI and 27 controls with a normal ovarian reserve were collected and analyzed using 16S rDNA sequencing and untargeted metabolomics. Conjoint analysis was performed to identify key microbial communities and metabolites that might be involved in POI.

Results: Patients with POI exhibited significant alterations in microbial richness and diversity and metabolic profile in their follicular fluid. The downregulation of ABC transporters and upregulation of the citrate cycle (TCA cycle) might be critical for the development and progression of POI. G-Rhodopseudomonas and g-Caulobacter were identified as key microbial genera, while L-aspartic acid, citrate, isoleucine, and cytidine were identified as key metabolites.

Discussion: These findings offer novel insights into the pathogenesis of POI and might pave the way for improved clinical outcomes for individuals with POI.