Endocrine最新文献

Purpose: Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk.

Methods: We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide.

Results: In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05).

Conclusions: In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

Objectives: Recurrence or tumor metastasis and drug resistance remain the major challenge in the treatment of thyroid cancer. It is needed to identify novel drug targets for thyroid cancer.

Methods: Summary data-based Mendelian randomization (SMR) and colocalization analysis were performed to evaluate the associations between gene methylation, expression, protein levels with thyroid cancer. We additionally performed protein-protein interaction (PPI) network, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to further explore the potential roles of identified genes in thyroid cancer.

Results: SDCCAG8 and VCAM1 genes were associated with risk of thyroid cancer with tier 1 evidence, while TCN2 gene was with tier 3 evidence. SDCCAG8 gene was associated with risk of papillary thyroid cancer with tier 1 evidence. At the level of circulating proteins, genetically predicted higher levels of SDCCAG8 (OR = 0.46, 95% CI 0.34-0.64) and VCAM1 (OR = 0.21, 95% CI 0.10-0.45) were inversely associated with thyroid cancer risk; higher level of TCN2 was associated with an increased risk of thyroid cancer (OR = 1.30, 95% CI 1.15-1.47); and the higher level of SDCCAG8 (OR = 0.40, 95% CI 0.28-0.58) was associated with a decreased risk of papillary thyroid cancer. The bioinformatics analysis showed that SDCCAG8, VCAM1 and TCN2 might play roles in immune-related pathways.

Conclusion: SDCCAG8, VCAM1 and TCN2 genes were associated with thyroid cancer risk with evidence at multi-omics levels. There were potential roles of SDCCAG8, VCAM1 and TCN2 in immune-related pathways. Our findings might improve the understanding of the pathogenesis of thyroid cancer and discovery of novel potential drug targets for this disease.

Purpose: Owing to the absence of the most recent evidence on the efficacy and safety of luseogliflozin, our study aimed to conduct a systematic review and meta-analysis of luseogliflozin in patients with type 2 diabetes mellitus.

Methods: A comprehensive search of electronic databases like PubMed, Cochrane CENTRAL, and Google Scholar was performed from the inception to the 31^st of August 2023 to identify the randomized controlled trials (RCTs) that examined the glucose and body weight lowering efficacy and safety outcomes of luseogliflozin in comparison with control or other active treatments. The fixed or random-effect model was used based on the heterogeneity identified using the I² statistic and Cochran's Q test.

Results: Out of 50 non-duplicate articles identified through database searching, 8 RCTs (11 studies) with 1922 patients were included in this study. The efficacy outcomes like HbA1c (MD: -0.59%; 95% CI: -0.90, -0.29; P < 0.001), FPG (MD: -16.01 mg/dL; 95% CI: -19.46, -12.57; P < 0.001), PPG (MD: -36.63 mg/dL; 95% CI: -43.71, -29.55; P < 0.001) and body weight (MD: -1.66 kg; 95% CI: -2.23, -1.12; P < 0.001) were significantly reduced with luseogliflozin compared to the control group. Regarding the safety outcomes, there was no statistically significant difference between the two groups for hypoglycemia (OR: 1.14; 95% CI: 0.70, 1.84; P = 0.60). However, pollakiuria (OR: 4.08; 95% CI: 1.71, 9.69; P < 0.001) and any ADRs (OR: 2.04; 95% CI: 1.33, 3.14; P < 0.001) were significantly higher in the luseogliflozin group compared to the control.

Conclusion: The current study identified a significant improvement in efficacy outcomes of HbA1c, FPG, PPG, and body weight in the luseogliflozin group. Non-significant safety results may be due to a smaller population size and fewer studies. Hence, long-term multicentric RCTs are needed to identify the safety and efficacy in a diversified population.

Purpose: ANGPTL8, commonly referred to as betatrophin, has demonstrated promise as a dependable marker for the onset of complications associated with diabetes mellitus, such as dyslipidemia. The objective of this study is to evaluate the lipid profile and ANGPTL8 levels in people diagnosed with Type 1 Diabetes Mellitus (T1DM).

Methods: A retrospective case-control study was performed on a group of 100 adolescent females, aged 13-17 years. This group consisted of individuals diagnosed with T1DM from the Diabetes and Endocrine Department at Medina's King Fahad Hospital in Saudi Arabia. Additionally, 100 healthy adolescent females of the same age range were included as controls. The hospital conducted laboratory studies to evaluate glucose, HbA1c, insulin, and lipid profiles. The ANGPTL8 levels were quantified using Enzyme-Linked Immunosorbent Assay (ELISA).

Results: Patients with T1DM had ANGPTL8 levels that were twice as high as those observed in individuals without any health conditions. The two groups had contrasting levels of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptides, triacylglycerol (TG), and cholesterol, along with elevated Atherogenic Index of Plasma readings. Diabetes mellitus patients had considerably elevated values compared to the control group. There was a significant correlation between ANGPTL8 concentrations and lipid abnormalities, with P-values less than 0.05. 56% of the 100 patients exhibited dyslipidemia. The research found a correlation between dyslipidemia and elevated levels of ANGPTL8 in diabetic patients. The concentration of ANGPTL8 had a positive correlation with glucose, HbA1c, TG, and C-peptides while displaying a negative correlation with high-density lipoprotein cholesterol (HDL-C).

Conclusion: ANGPTL8 levels were found to be elevated in Saudi young women who were diagnosed with TIDM. ANGPTL8 may potentially contribute to dyslipidemia in individuals with T1DM, hence increasing the susceptibility to cardiovascular disease (CVD). Therefore, ANGPTL8 has the potential to impact lipid metabolism, namely Triglycerides, as a biological route. The results highlight the need to analyze lipid profiles and do ANGPTL8 testing in young females diagnosed with T1DM at an early stage to prevent complications.

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications.

Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]).

Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712]).

Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria.

Purpose: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness.

Methods: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews.

Results: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis.

Conclusion: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

Background: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture.

Aims: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA).

Methods: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture.

Results: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76).

Conclusions: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

Purpose: Ethylene oxide (EO) is a prevalent industrial contaminant found in the environment and is related to various diseases such as cancers and hypertension. To the best of our knowledge, the association between EO and testosterone has not been explored. The aim of this article was to evaluate the relationship between EO and total testosterone (TT) in the United States population.

Methods: In this study, hemoglobin ethylene oxide (HbEO) levels were utilized to evaluate the exposure to EO. The data of this study were collected from National Health and Nutrition Examination Survey (NHANES) 2013-2016. A total of 3300 participants were enrolled in this study and were separated into 5 groups based on the quintile of HbEO. Weighted multivariable logistic regression was used to assess the association between HbEO and TT. Subgroup analysis was conducted to investigate the connection between HbEO and TT in different stratifications.

Results: In the results, there was a positive relationship between log₁₀-transformed HbEO and TT in the fully adjusted model [β = 37.08, 95% confidence interval (CI): 18.15-56.01, p = 0.004]. After log₁₀-transformed HbEO transferred into a categorical variable based on the quintiles (Q1-Q5), the positive association remained in the highest group (Q5) compared to the lowest group (Q1) [β = 46.09, 95%CI: 12.29-79.90, p = 0.013]. Moreover, subgroup analysis demonstrated that the positive connection between log₁₀-transformed HbEO and TT was stronger in males than females.

Conclusion: The level of HbEO was positively related to TT in the U.S. population and the relation was more obvious in men compared to women.

Purpose: This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto's thyroiditis (HT) patients.

Methods: A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT.

Results: Among these 272 patients, 40 (14.7%) were diagnosed with IgG4 HT. Patients with IgG4 HT were younger than those with non-IgG4 HT (P < 0.05). Serum levels of TgAb IgG4 and TPOAb IgG4 in IgG4 HT group were significantly higher than those in non-IgG4 HT group (P < 0.05). There were no significant differences in gender, disease duration, goiter, preoperative thyroid function status, preoperative TgAb or TPOAb levels, and thyroid ultrasound characteristics between the two groups (all P > 0.05). The accuracy, sensitivity, and specificity were 57%, 78%, and 79% for logistic regression model of IgG4 HT, 80 ± 7%, 84.7% ± 2.6%, and 75.4% ± 9.6% for the RF model and 78 ± 5%, 89.8% ± 5.7%, and 64.7% ± 5.7% for the SVM model. The RF model works better than SVM. The area under the ROC curve of RF ranged 0.87 to 0.92.

Conclusion: A clinical diagnosis model for IgG4 HT established by RF model might help the early recognition of the high-risk patients of IgG4 HT.