Frontiers in Endocrinology最新文献

Context/objectives: Hydroxychoroquine has hypoglycemic effects and may reduce the risk of diabetes mellitus (DM). We determined the association between hydroxychoroquine use and the incidence of DM in a population-based cohort of pations with Rheumatic disease.

Methods: A prospective cohort study among 502392 Potentially eligible participants in the context of UK Biobank, recruitment to the database began between 2006 and 2010. Patients diagnosed with diabetes and fasting glucose greater than or equal to 7 mmol/L at baseline (n=619) were excluded and patients diagnosed with either RA or SLE at baseline (n=6793) were followed up until 2022. Diagnosis was recorded using the International Classification of Diseases, tenth edition (ICD-10) code. The mean follow-up was 13.78 years and the primary outcome was newly recorded type 2 diabetes mellitus (T2DM), with the time of onset of diabetes as the follow-up endpoint date.

Results: During a median follow-up period of 13.78 (12.93, 14.49) years, diabetes developed in 537 participants, with an incidence of 7.9%. New diabetes cases not taking hydroxychloroquine and taking hydroxychloroquine was 504 (8.03%) and 33 (6.36%), respectively. In univariate models, the hazard ratio for diabetes was 0.89 (95% confidence interval, 0.81-0.98, P=0.014) for hydroxychloroquine users compared with those not taking hydroxychloroquine. After adjusting for age, sex, race, education level, and BMI the hazard ratio for incident diabetes among hydroxychloroquine users was 0.88 (95% confidence interval, 0.80-0.97, P=0.008). In complete multivariate model hazard ratio for hydroxychloroquine was 0.87 (95% confidence interval, 0.79- 0.96, P=0.005).

Conclusion: Hydroxychloroquine was associated with decreased risk of DM among rheumatoid arthritis patients, our data taken together with correlational studies, warrant further investigation of the potential preventive effect of hydroxychloroquine against T2DM.

Background: The comorbidity of chronic pancreatitis (CP) in patients with osteoarthritis (OA) is insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of CP in OA patients, as well as associated complications.

Methods: A cohort of 181 patients was categorized into four groups: a control group (n=30), patients with OA (n=68), patients with CP (n=31), and patients with OA and comorbid CP (n=52). All four groups had no statistical differences in age and gender. The study utilized the WOMAC index, Visual Analog Scale (VAS), Lequesne index, biochemical assays, and advanced statistical methods to assess joint status in OA patients with comorbid CP. It explored potential predictors of comorbidity development and associated complications.

Results: The study revealed that concurrent CP in OA exacerbates progression and contributes to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for CP comorbidity development in OA patients. Factors such as the WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxyvitamin D3, and BMI were found to influence the development of comorbidity of CP in OA. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation Syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency Domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors comorbidity CP with exocrine pancreatic insufficiency in OA patients.

Conclusion: The presence of CP in OA patients exacerbates disease progression and complications, necessitating further investigation.

A new diagnosis of type 1 diabetes (T1D) may be accompanied by numerous lifelong financial, emotional, and physical challenges, thus advancements in therapies that can delay the onset of clinical disease are crucial. T1D is an autoimmune condition involving destruction of pancreatic beta cells leading to insulin deficiency, hyperglycemia, and long-term insulin dependence. The pathogenesis of T1D is classified into stages, with the first signal being the detection of autoantibodies without any glycemic changes. In the second stage, dysglycemia develops without symptoms, and in stage 3, symptoms of hyperglycemia become apparent, and at this time a clinical diagnosis of T1D is made. As a greater understanding of these stages of T1D have evolved, research efforts have been devoted to delaying the onset of clinical disease. To date, only one medication, teplizumab, has been approved by the Food and Drug Administration (FDA) for the treatment of stage 2 T1D. This narrative review present published trials and ongoing research on disease modifying therapies (DMT) in T1D, the mechanisms of action for each therapy, and the stages of T1D that these interventions are being studied.

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Background: Informative biomarkers play a vital role in guiding clinical decisions regarding management of cancers. We have previously demonstrated the potential of a deep convolutional neural network (CNN) for predicting cancer driver gene mutations from expert-curated histopathologic images in papillary thyroid carcinomas (PTCs). Recognizing the importance of whole slide image (WSI) analysis for clinical application, we aimed to develop an automated image preprocessing workflow that uses WSI inputs to categorize PTCs based on driver mutations.

Methods: Histopathology slides from The Cancer Genome Atlas (TCGA) repository were utilized for diagnostic purposes. These slides underwent an automated tile extraction and preprocessing pipeline to ensure analysis-ready quality. Next, the extracted image tiles were utilized to train a deep learning CNN model, specifically Google's Inception v3, for the classification of PTCs. The model was trained to distinguish between different groups based on BRAF^V600E or RAS mutations.

Results: The newly developed pipeline performed equally well as the expert-curated image classifier. The best model achieved Area Under the Curve (AUC) values of 0.86 (ranging from 0.847 to 0.872) for validation and 0.865 (ranging from 0.854 to 0.876) for the final testing subsets. Notably, it accurately predicted 90% of tumors in the validation set and 84.2% in the final testing set. Furthermore, the performance of our new classifier showed a strong correlation with the expert-curated classifier (Spearman rho = 0.726, p = 5.28 e-08), and correlated with the molecular expression-based classifier, BRS (BRAF-RAS scores) (Spearman rho = 0.418, p = 1.92e-13).

Conclusions: Utilizing WSIs, we implemented an automated workflow with deep CNN model that accurately classifies driver mutations in PTCs.

Choline kinase alpha (ChoKα) is a therapeutic target being developed for a variety of diseases, from cancer to rheumatoid arthritis and from parasites to bacterial infections. Nevertheless, the therapeutic potential of this drug target seems not exhausted and may end up as a possible solution for a larger variety of conditions. Here we present our working model for how ChoKα could play a role in obesity and for how drugs being developed as therapeutics for other diseases using ChoKα as a target, could be repurposed as prophylactic treatments for obesity. We also present preliminary observations in support of our model.

Objective: To evaluate the association between Erectile dysfunction (ED) and peripheral arterial disease (PAD) in adult American males using a large database.

Methods: The relationship between ED and PAD prevalence among participants in the 2001-2004 National Health and Nutrition Examination Survey (NHANES) database was assessed using a series of statistical analyses. ED was evaluated based on a single-item measure of self-reported erection problems from the Massachusetts Male Aging Study. PAD was defined as ankle-brachial index (ABI) < 0.9 in at least one leg. Multifactorial logistic regression models were used to investigate the association between ED and PAD.

Results: A total of 2394 participants were enrolled, of whom 905 individuals (37.8%) were diagnosed with ED. After adjusting for confounding variables, the association between ED and PAD remained positive, with an odds ratio of 2.05 (95% confidence interval 1.24-3.39). Subgroup analysis revealed that the relationship between ED and PAD was significant in patients aged >50 years old, without hypertension, without diabetes, without cardiovascular disease, without high cholesterol, former smokers, low physical activity levels, and a body mass index of 25-30 (P < 0.05). In addition, all subgroups analyzed were evaluated for any potential interaction, and no statistically significant association was discovered.

Conclusions: In a sample of US adults aged ≥40, this cross-sectional study found that ED is related to a higher occurrence of PAD. ED may be an independent predictor of PAD, and thus it should be considered in the treatment of patients with ED.

Objective: This study seeks to elucidate the dynamic alterations in the multifidus, erector spinae, and psoas major muscles, along with their fatty infiltration, in patients diagnosed with lumbar disc herniation treated through acupuncture. Concurrently, the Visual Analogue Scale (VAS) and Japanese Orthopedic Association (JOA) scores are employed to evaluate modifications in lumbar and leg pain and the enhancement in lumbar functionality.

Methods: A retrospective multi-center cohort study enrolled 332 adult LDH patients. Participants were divided into acupuncture and rehabilitation therapy groups. The acupuncture cohort received targeted treatments at specific acupuncture points, while the rehabilitation group received traditional rehabilitative therapy. Magnetic Resonance Imaging (MRI) gauged muscle cross-sectional areas (Sm, Se, Sp) and their ratios to vertebral area (Sm/Sv, Se/Sv, Sp/Sv), and fatty infiltration areas (Sfm, Sfe, Sfp) and their ratios (Sfm/Sv, Sfe/Sv, Sfp/Sv). Pain and function were assessed using Visual Analogue Scale (VAS) and Japanese Orthopedic Association (JOA) scores pre-treatment, 2-weeks, and 3-months post-intervention.

Results: A total of 332 patients were enrolled for analysis. Post-treatment, the acupuncture group exhibited increased Sm, Se, Sp and their ratios and reduced fatty infiltration areas and their ratios (P<0.05) compared to rehabilitation. Both treatments decreased VAS scores and enhanced JOA scores at both intervals (P<0.05). Intriguingly, no significant disparities were observed between the acupuncture and rehabilitation groups concerning pain and JOA scores at the 2-week follow-up (p>0.05); however, 3 months post-treatment, the acupuncture group significantly outperformed the rehabilitation group in both pain and JOA scores (p<0.05).

Conclusion: This study demonstrates that acupuncture treatment is significantly more effective than traditional rehabilitation therapy in improving paraspinal muscle function, reducing muscle fat infiltration, and alleviating lumbar and leg pain in patients with lumbar disc herniation (LDH). Specifically, acupuncture significantly increases the cross-sectional areas (Sm, Se, Sp) of the paraspinal muscles and reduces muscle fat infiltration, showing superior long-term results in pain relief and functional improvement. Future research should further explore the long-term effects of acupuncture on the function and structure of paraspinal muscles, assess its potential in preventing the recurrence of LDH, and delve deeper into how acupuncture affects paraspinal muscles at the molecular level, to better understand its therapeutic mechanisms and enhance its clinical application.

Background: Graves' disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.

Methods: Single-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed.

Results: There were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025-1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870-1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D.

Conclusion: There was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D.