International Journal of Endocrinology最新文献

Background: The association of vitamin D with metabolic dysfunction-associated fatty liver disease (MAFLD) remained unclear. This study aimed to examine the relationships of total 25-hydroxyvitamin D [25(OH)D, the sum of 25(OH)D₂ and 25(OH)D₃], 25(OH)D₃, and epi-25(OH)D₃ with MAFLD. Methods: We used the National Health and Nutrition Examination Survey of the 2017-2018 cycle for our present analysis. Binary logistic regression analyses were conducted to explore the associations of total 25(OH)D, 25(OH)D₃, and epi-25(OH)D₃ with MAFLD after adjusting for confounders. Interaction tests were conducted to compare the association between 25(OH)D and MAFLD in subgroups. Results: The final analysis included 4605 subjects. After adjustment for confounders, the odds of MAFLD decreased with increasing concentrations of total 25(OH)D (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.29-0.68; p for trend < 0.001). Serum 25(OH)D₃ showed a strong inverse association with MAFLD (OR, 0.39; 95% CI, 0.25-0.59; p for trend < 0.001). In addition, participants with lower epi-25(OH)D₃ levels had a higher likelihood of MAFLD, as demonstrated in both quartile and continuous models (OR, 0.77; 95% CI, 0.60-0.99; p=0.041). After stratification by lipid status, inverse associations of total 25(OH)D and 25(OH)D₃ with MAFLD were found only in dyslipidemic participants (p for interaction < 0.001). A sex-specific interaction was also noted for 25(OH)D₃, showing stronger effects in women than in men (p=0.036). Conclusions: Low serum total 25(OH)D, 25(OH)D₃, and epi-25(OH)D₃ were significantly associated with a higher prevalence of MAFLD. These associations showed nonlinear patterns and were particularly evident among participants with dyslipidemia, with 25(OH)D₃ demonstrating stronger protective effects in women than in men. Given the cross-sectional design, causality cannot be inferred, and further prospective studies are required to confirm these findings.

Purpose: To explore the flavin-containing monooxygenase 3 (FMO3) single-nucleotide polymorphisms (SNPs) and their connection to coronary heart disease (CHD) among Han Chinese with type 2 diabetes (T2D). Methods: The case-control research involved 781 individuals with T2D: 506 CHD cases and 275 controls. The tag-SNPs rs2266780, rs1736557, rs1800822, and rs909530 were selected according to the e!Ensembl database. The genotypes of all the research populations were analyzed via mass spectrometry. SPSS 25.0 software was used to analyze the associations between the selected SNPs and the risk of developing CHD. Results: The rs1800822 T allele frequency was lower in the CHD group than in the non-CHD group (p = 0.049), as was the rs909530 T allele frequency (p = 0.029). The carriers of rs909530 CX genotype had a greater risk of developing CHD than did the TT genotype carriers in the non-premature CHD group (p < 0.001). Conclusion: Our study revealed that rs1800822 and rs909530 in the FMO3 gene may be related to CHD risk among Han Chinese with T2D. We observed a significant gene-by-age interaction at rs909530 on CHD risk, indicating that aging modulates the effect of this locus. Young patients with T2D and the CX genotype may require more stringent management of cardiovascular risk factors.

Background: The selection of thyroid nodules ≤ 10 mm requiring characterization and treatment should be improved, as extensive detection, cytological assessment, and surgery of small and well-differentiated thyroid carcinoma are not cost-effective. Aim: To assess the accuracy of algorithms and ultrasonographic characteristics in selecting actual high-risk thyroid nodules ≤ 10 mm. Methods: A cross-sectional study was conducted on 38 of 112 outpatients who attended the University of Bari and underwent echo-assisted FNA for cytological characterization of thyroid nodules ≤ 10 mm (65 out of 118) and thyroid surgery from January 01 to December 31, 2016. Results: The median age of patients was 49.5 years [16; 69]. Thyroid cytology (SIAPeC-IAP 2014) was classified as TIR1 (one nodule), TIR2 (15), TIR3A (7), TIR3B (10), TIR4 (8), and TIR5 (24). Thirty-nine thyroid nodules were diagnosed as well-differentiated thyroid microcarcinoma. The clinical performance of 4 algorithms widely employed in clinical practice was low (AACE/ACE/AME, 38%; ACR-TIRADS, 45%; K-TIRADS, 60%; EU-TIRADS, 66%). Ultrasonographic features indicating high-risk nodules were hypoechogenicity (p=0.0047), irregular margins (p=0.004), and microcalcifications (p=0.0019). Multivariable analyses indicated that hypoechogenicity was the main ultrasonographic characteristic associated with high-risk nodules (OR = 5.48, p=0.0484). Discussion: Validated algorithms fail to select thyroid nodules ≤ 10 mm for which cytological characterization is needed. Our results are expected to improve the reliability of current algorithms by improving the weight of variables associated with a more consistent risk of thyroid malignancy in nodules ≤ 10 mm.

Purpose: Dietary and exercise interventions have the potential to modify thyroid hormone levels in individuals with obesity. This study investigates the specific mechanisms through which these interventions influence thyroid function, employing a multiomics approach. Methods: 16 volunteers with obesity participated in a two-week regimen of aerobic exercise combined with dietary control. Fasting blood samples and anthropometric measurements were taken before and after the intervention. Serum untargeted lipidomics and metabolomics analyses were performed, alongside evaluations of serum thyroid hormone levels. Additionally, an RNA sequencing dataset was obtained which included gene expression data for skeletal muscle and subcutaneous fat both prior to and following weight loss. Results: Following the intervention, significant alterations were observed in serum levels of thyroid hormones, lipid molecules, and metabolites among participants. Notably, there was a substantial reduction in the levels of tyrosine and phenylalanine (p < 0.001). Furthermore, this intervention had a pronounced effect on the activity of thyroid hormone signaling pathways. Conclusion: Dietary modifications along with exercise facilitate the restoration of thyroid function by enhancing the consumption of tyrosine and phenylalanine while concurrently altering the activity within thyroid hormone signaling pathways. These findings provide valuable insights into potential treatments for obesity-related thyroid dysfunction. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2000040981.

Background: Diabetes mellitus (DM) is a growing concern globally. DM control is indicated by hemoglobin A1c, measuring glucose levels within two to 3 months. Patients with DM who have surgery may experience postoperative hyperglycemia (POHG) which is associated with many complications. This study aimed to investigate POHG incidence among patients with DM based on their level of glycemic control. Methods: This was a retrospective cohort study of patients with DM ≥ 18 years who had orthopedic, intra-abdominal, cardiothoracic, or vascular surgery at King Abdulaziz Medical City, Jeddah, between October 2016 and October 2023. Patients with DM were considered controlled if the hemoglobin A1c was < 7%. Results: The study included 306 patients, and the majority (69.28%) experienced POHG. There was a significant association between POHG and the level of glycemic control. POHG was experienced by 32.55% of patients with controlled DM vs 67.45% of patients with uncontrolled DM. Furthermore, patients with preoperative random glucose readings (RBG) of ≥ 9.2 mmol/L had a significantly higher risk of developing POHG. Moreover, older age and male sex were associated with higher POHG risk. Conclusion: Our data indicate that the incidence of POHG was significantly greater among patients with uncontrolled DM. Patients with DM with a preoperative RBG of ≥ 9.2 mmol/L had a higher likelihood of developing POHG. Future research should include a larger sample and investigate associations between POHG, other complications, and the influence of varying levels of DM control.

Objective: Primary hyperparathyroidism can be cured by the successful removal of the culpable parathyroid adenoma. Successful localisation allows the specialist surgeon to perform safer and more cost-effective focused excisions rather than exploratory surgery. This study aims to identify possible factors that predict successful adenoma localisation using technetium99m-sestamibi. Design, Patients and Measurements: Retrospective analysis of 159 patients undergoing parathyroid localisation with technetium99m-sestamibi SPECT/CT. Patients were classified as successful or unsuccessful localisation when compared to the surgical site of a proven adenoma following successful parathyroidectomy. Preoperative and postoperative serum parathyroid hormone (PTH), calcium and 25-hydroxyvitamin D levels and pathological size of the parathyroid adenoma were recorded. Results: Larger specimen volume, weight and higher preoperative PTHs were strongly associated with successful localisation. The percentage change in serum calcium (calculated as the difference between pre- and post-op calcium) was also strongly associated with successful localisation. Higher preoperative serum calcium (> 2.85 mmol/L) was also associated with successful localisation although with a reduced statistical significance. Seventy percent of patients in our cohort underwent parathyroidectomy with a serum calcium < 2.85 mmol/L, of which 92% had pathologically confirmed adenomas and 67% had successful localisation with sestamibi. Conclusion: The serum PTH and change in serum calcium were most strongly associated with successful localisation. The degree of hypercalcaemia was also associated with successful localisation but without as strong an association when compared to the change in calcium. Several factors influence the degree of hypercalcaemia in patients with primary hyperparathyroidism including parathyroid adenoma size, 25-hydroxyvitamin D status and the individual's baseline calcium set point. Historic information (if available) on the patient's individual baseline set point prior to developing primary hyperparathyroidism, and subsequent elevation when primary hyperparathyroidism has developed, could aid decision-making for clinicians when deciding on parathyroidectomy.

Background: Few parameters are available for diagnosing renal potassium loss in emergency patients or patients receiving treatment. This study aimed to investigate the ratio of random urine potassium‒creatinine to the synchronous serum potassium concentration squared ([UK/UCr]/SK²) and compare it with other parameters in the diagnostic ability of renal potassium loss. Methods: This single-center study enrolled 380 subjects, including 218 hypokalemia patients (91 with nonrenal potassium loss and 127 with renal potassium loss) and 162 normal potassium controls. The values of serum and urine were based on laboratory data. Groups were compared in pairs, and the ROC curve analysis was used to evaluate the predictive ability of parameters related to renal potassium loss. Results: (UK/UCr)/SK² was significantly elevated in potassium loss patients, especially in females. Moreover, a greater (UK/UCr)/SK² ratio was observed in those with nonrenal potassium loss, which demonstrated a trend toward increases in the normal potassium, nonrenal potassium loss, and renal potassium loss groups among males and females. Ultimately, the AUC of (UK/UCr)/SK² was the highest at 0.880 (95% CI: 0.822-0.938) in males and 0.878 (95% CI: 0.831-0.924) in females for potassium loss diagnosis. Conclusion: Random (UK/UCr)/SK² has good diagnostic value for renal potassium loss in patients with hypokalemia. Given that these serum and random urine parameters are easily obtainable from patients during treatment, regularly observing (UK/UCr)/SK² may prove to be an effective indicator.

Background: Socioeconomic status (SES) influences a wide range of health outcomes, including hepatic steatosis and liver fibrosis, which are increasingly concerning. The aim of the study was to investigate the association between SES and hepatic steatosis and liver fibrosis and examine the potential mediating effects of body mass index (BMI) in this association. Methods: We used the National Health and Nutrition Examination Survey (NHANES) 2021-2023 data to conduct a cross-sectional study. Occupation, insurance, family income level, and education level were employed as indicators of SES. Hepatic steatosis and liver fibrosis were quantified by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Mediation analysis was used to estimate the direct and indirect associations of SES with hepatic steatosis and liver fibrosis through BMI after adjustment for potential confounders. Results: The study included 4455 participants. Compared to individuals with low SES, those with high SES had a lower risk of hepatic steatosis (odds ratios [OR] = 0.80, 95% CI: 0.69-0.94, p < 0.01) and liver fibrosis (OR = 0.77, 95% CI: 0.61-0.97, p=0.03). However, after adjusting for confounding factors, the associations were no longer statistically significant (hepatic steatosis: OR = 0.90, 95% CI: 0.75-1.08, p=0.25; liver fibrosis: OR = 0.87, 95% CI: 0.67-1.15, p=0.32). BMI differed significantly across SES grades (p=0.04). Restricted cubic spline analysis revealed a significant nonlinear positive association between BMI and hepatic steatosis (p < 0.01), and a linear positive association with liver fibrosis (p=0.11). Moreover, BMI accounted for 32.8% of the mediation effect between SES and hepatic steatosis and 18.2% of the mediation effect between SES and liver fibrosis. Conclusion: People with higher SES are less likely to develop hepatic steatosis and liver fibrosis, although the associations were attenuated after adjustment for confounding factors. SES might contribute to hepatic steatosis and liver fibrosis through the involvement of BMI.

Background: Osteoporosis is a progressive bone disease characterized by reduced bone density and deterioration of bone microarchitecture, predominantly affecting the elderly population. The ongoing COVID-19 pandemic has introduced additional challenges in osteoporosis management, potentially due to systemic inflammation and direct viral impacts on bone metabolism. This study aims to identify common differentially expressed genes (DEGs) and key molecular pathways shared between osteoporosis and COVID-19, with the goal of uncovering potential therapeutic targets through bioinformatics analysis. Methods: Publicly available gene expression datasets GSE164805 (osteoporosis) and GSE230665 (COVID-19) were analyzed to identify overlapping DEGs. Functional enrichment analysis using Gene Ontology (GO), pathway analysis, protein-protein interaction (PPI) network construction, and transcription factor (TF)-hub gene regulatory network analysis were performed to explore the biological significance and regulatory mechanisms of these DEGs. Results: A total of 325 common DEGs were identified between osteoporosis and COVID-19. GO enrichment analysis revealed significant involvement in signal transduction and plasma membrane components. Pathway analysis highlighted the "cytokine-cytokine receptor interaction" pathway as a central player. PPI network analysis identified a module of 193 genes with 397 interactions, from which 10 key hub genes were prioritized: ACTB, CDH1, RPS8, IFNG, RPL17, UBC, RPL36, RPS4Y1, GSK3B, and FGF13. Furthermore, 76 TFs were found to regulate these hub genes, and 15 existing drugs targeting four of these hub genes were identified. Conclusion: This integrative bioinformatics study reveals 15 candidate therapeutic agents that target key regulatory genes shared between osteoporosis and COVID-19, offering promising treatment strategies for osteoporotic patients, especially those impacted by or at risk of SARS-CoV-2 infection.

Aims: Dipeptidyl peptidase-4 (DPP4) inhibitors are commonly used to treat type 2 diabetes. However, the causality of it on cardiovascular diseases (CVDs) is controversial. This study aimed (1) to investigate the causal mechanisms of DPP4 gene expression at the mRNA level on CVDs, including all-cause heart failure (HF), atrial fibrillation (AF), myocardial infarction (MI), and stroke in a European population; (2) to assess the direct effect of DPP4 at the mRNA level on CVD, which is independent of type-2 diabetes; and (3) to explore the causality of DPP4 inhibition on CVDs and type-2 diabetes. Methods: Utilizing DPP4 and CVD summary statistics from eQTLGen Consortium, GTEx Portal, and UK Biobank, we applied weak IV and pleiotropy robust Mendelian randomization methods (MR-RAPS, GRAPPLE, BESIDE-MR, debiased IVW) and mediation analysis to assess the causal impact of DPP4 at the mRNA level on CVD and the direct effect of DPP4 at the mRNA level on CVD, not mediated by diabetes. The causality of DPP4 inhibition on CVD was also evaluated. Results: MR-RAPS suggested a potential causal relationship between increased DPP4 at the mRNA levels and HF (0.031 [95% CI, 0.06-0.56; p=0.014]). However, there was limited evidence that increased DPP4 levels affect AF, MI, or stroke. Other analyses corroborated these findings. Mediation analysis indicated a direct effect of DPP4 at the mRNA level on HF, while debiased IVW showed limited evidence for a causal effect of DPP4 inhibition on CVDs, possibly due to low statistical power. Conclusions: Mendelian randomization analyses support the cardiovascular safety of DPP4 inhibitors in managing type 2 diabetes, with little evidence for DPP4-mediated cardiovascular harm, reinforcing their appropriateness for clinical use in European populations. Additionally, if DPP4 inhibition affects cardiovascular outcomes, it may not do so through glycemic control, such as HbA1c reduction.