Endocrine最新文献

Purpose: Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population.

Methods: This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals.

Results: Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders.

Conclusion: OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks.

Purpose: To perform a molecular profiling of the metastases from papillary thyroid carcinomas (PTCs) and poorly differentiated thyroid carcinomas (PDTCs).

Methods: We retrieved and analyzed the molecular and clinical features of 136 metastases from PTCs and 35 metastases from PDTCs subjected to targeted DNA sequencing, from cBioPortal. The clinicopathological data included the number and location of the metastases, and genomic data included mutations, translocations, copy number alterations and fraction of the genome altered (FGA).

Results: Bone metastases from PTCs had a lower frequency of BRAF mutations than the lymph node metastases (LNMs) (43% vs 88%, p < 0.01), and a higher frequency of RBM10 and NRAS mutations than the LNMs (21% vs 3% for both, p < 0.05). The FGA of the bone metastases was higher than the FGA of the lung metastases (5.6% vs 1.3%, p < 0.05). The frequency of RET translocations was higher in the lung metastases from PTCs than the LNMs (15% vs 3%, p < 0.05). The LNMs from PTC patients harboring 4 or more distant metastases (DMs) had a higher frequency of TERT promoter mutations than the LNMs from patients harboring less than 4 DMs (96% vs 65%, p < 0.001). SDHA gene amplifications were enriched in the bone metastases from PDTCs and absent in the LNMs (38% vs 0%, p < 0.05).

Conclusion: Metastases from PTCs and PDTCs harbor clinically relevant alterations affecting distinct body locations, such as NRAS and RBM10 mutations, RET translocations and SDHA amplifications that may be explored therapeutically.

Purpose: This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets.

Methods: Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS).

Results: Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25.

Conclusion: For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic β-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.

Objectives: This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity.

Methods: A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors.

Results: NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001).

Conclusions: In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity.

Introduction: Diabetes and neuronal loss in the hippocampus have been observed to be correlated in several studies; however, the exact causality of this association remains uncertain. This study aims to explore the potential causal relationship between diabetes and the hippocampal nervous system.

Methods: We utilized the two-sample Mendelian randomization (MR) analysis to investigate the potential causal connection between diabetes and the hippocampal nervous system. The summary statistics of Genome-wide association study (GWAS) for diabetes and hippocampus neuroimaging measurement were acquired from published GWASs, all of which were based on European ancestry. Several two-sample MR analyses were conducted in this study, utilizing inverse-variance weighted (IVW), MR Egger, and Weight-median methods. To ensure the reliability of the results and identify any horizontal pleiotropy, sensitivity analyses were undertaken using Cochran's Q test and the MR-PRESSO global test.

Results: Causal associations were found between diabetes and the nervous system in the hippocampus. Type 1 and type 2 diabetes were both identified as having adverse causal connections with the right hippocampal nervous system. This was supported by specific ranges of IVW-OR values (P < 0.05). The consistency of the sensitivity analyses further reinforced the main findings, revealing no significant heterogeneity or presence of horizontal pleiotropy.

Conclusions: This study delved into the causal associations between diabetes and the hippocampal nervous system, revealing that both type 1 and type 2 diabetes have detrimental effects on the right hippocampal nervous system. Our findings have significant clinical implications as they indicate that diabetes may play a role in the decline of neurons in the right hippocampus among European populations, often resulting in cognitive decline.

Purpose: To explore the relationship between glucose management indicator (GMI) and HbA1c and find the affecting factors in adult T2D patients with good glycemic control.

Methods: Adult T2D patients with both HbA1c < 7% and time in range (TIR) > 70% were retrospectively analyzed. A significant difference between GMI and HbA1c was defined as an absolute value of hemoglobin glycation index (|HGI|, HbA1c minus GMI) ≥ 0.5%. Factors associated with high |HGI| were determined by logistic regression analysis. The performance of possible factors in predicting high |HGI| was verified by ROC curve analysis. And the linear relationship between GMI and HbA1c was also investigated.

Results: Of all the 94 patients (median HbA1c 6.18%, mean GMI 6.34%) included, 28.72% had an |HGI | ≥ 0.5% and only 15.96% had an |HGI | < 0.1%. Standard deviation of blood glucose (SDBG), a glycemic variability index, affected |HGI| (OR = 3.980, P = 0.001), and showed the best performance in predicting high |HGI| (AUC = 0.712, cutoff value = 1.63 mmol/L, P = 0.001). HbA1c was linearly correlated with GMI (β = 0.295, P = 0.004). Their correlation weakened after further adjusting for SDBG (β = 0.232, P = 0.012). Linear correlation between them was closer in patients with smaller SDBG ( < 1.63 mmol/L) than those with larger SDBG (P = 0.004).

Conclusions: Even in adult T2D patients with good glycemic control, the discrepancy between GMI and HbA1c existed. Their relationship was affected by glycemic variability. SDBG mainly accounted for this consequence.

Trial registration: Chinese clinical trial registry ( www.chictr.org.cn ), ChiCTR2000034884, 2020-07-23.

Purpose: An improvement in iodine status in the Veneto region (Italy) in the last decade has been documented. Our aim was to estimate the incidence of autoimmune thyroiditis (AT) in this region over the period 2012-2022.

Methods: A retrospective population-based study conducted in Veneto using the population registry and administrative health databases. We documented incident hyperthyroidism from 2013 to 2022 to exclude prevalent cases and calculated standardised incidence rates (IR) per 10,000 person-years by age and sex.

Results: We identified 65,379 incident cases (IR: 13.38), 5.44-fold higher in females than in males. IR decreased from 15.86 (95% CI: 15.50, 16.21) in 2013 to 12.35 (95% CI: 12.04, 12.67) in 2022. The decline was evident only in females, with a documented reduction in IR from 27.26 (95% CI: 26.61, 27.91) in 2013 to 20.49 (95% CI: 19.92, 21.07) in 2022 (P = 0.002). The decrease was sharper in females aged 15-54 years (IR from 37.86 (95%CI: 36.79, 38.94) in 2013 to 27.40 (95% CI: 26.44, 28.36) in 2022; P < 0.001) than in those aged ≥55 years (IR from 20.06 (95% CI: 19.13, 20.99) in 2013 to 16.56 (95% CI: 15.78, 17.35) in 2022; P = 0.034). In 2020, an out-of-trend decrease in AT incidence was documented, corresponding with the SARS-CoV-2 pandemic, with a realignment to the trend in the subsequent years.

Conclusions: A decline in AT was documented in the Veneto region in the last decade, paralleling improvement in the iodine status. The reduction was significant only among females, particularly in reproductive age.

Objective: This study aims to investigate the role of TRAb in the angiogenesis associated with Graves' disease (GD) and to elucidate its underlying mechanisms.

Methods: Human thyroid follicular epithelial cells (Nthy-ori 3-1) and human umbilical vein endothelial cells (HUVECs) were treated with the monoclonal thyroid-stimulating antibody M22 and thyroid-stimulating hormone (TSH) at various concentrations. Cell viability, migration, and tube formation were evaluated using CCK-8, wound healing, and tube formation assays, respectively. Protein expressions of TSHR receptor (TSHR) and phosphorylated AKT (p-AKT) in M22-induced HUVECs were quantified via Western blotting. Proteomic analysis was employed to identify changes in protein expression profiles and relevant signaling pathways in GD specimens. Immunofluorescence assays were conducted to detect and localize the expressions of CD34 and PROX1 in GD specimens and normal thyroid tissues.

Results: M22 stimulated the proliferation of Nthy-ori 3-1 cells and HUVECs in a dose-dependent manner, while TSH exhibited an inverted U-shaped dose-response effect. M22 also dose-dependently promoted angiogenesis, and more effectively induced tube formation in HUVECs compared to TSH, although the difference was not statistically significant. A total of 16 proteins were significantly upregulated and 24 were downregulated in M22-induced HUVECs. Notably, PROX1, the most significantly upregulated protein, is closely associated with angiogenesis. Immunofluorescence confirmed that PROX1 was significantly more expressed in thyroid tissues from GD patients compared to normal tissues adjacent to papillary thyroid cancer (PTC), and it co-localized with CD34.

Conclusion: TRAb enhances angiogenesis and upregulates PROX1 expression in HUVECs, suggesting a novel possible mechanism for goiter formation in GD.

Hypothyroidism is typically treated with levothyroxine monotherapy. However, despite normalized serum thyroid-stimulating hormone levels, 5-10% of patients continue to experience persistent symptoms, raising concerns about the adequacy of thyroxine monotherapy. Combination therapy with levothyroxine and liothyronine has been proposed as an alternative, but it presents practical challenges, including dosing complexity, the short half-life of triiodothyronine, increased monitoring requirements, and potential adverse effects. Moreover, there is no clear consensus within the medical community regarding the superiority of combination therapy over levothyroxine monotherapy, although some studies indicate potential benefits in specific patient populations. Genetic factors, such as polymorphisms in the DIO2 gene, may influence individual responses to therapy, further complicating treatment. To address the limitations of combination therapy, we propose a novel approach: TTCombo. This digital health technology delivers personalized doses of levothyroxine and liothyronine, improving treatment adherence and optimizing outcomes. By providing individualized, physiologically tailored hormone replacement, TTCombo has the potential to revolutionize hypothyroidism management and enhance patient quality of life.

Background: The types of growth hormone-secreting pituitary adenomas are diverse, we have found that there are significant differences in clinical features and prognosis between PIT-1 single-cell spectrum growth hormone adenomas and growth hormone phenotypic polyhormonal adenomas.

Methods: This study examined a cohort of 193 patients with growth hormone-secreting pituitary adenoma (GHPA), stratifying them into two groups: PIT-1 single transcription factor positive growth hormone adenoma (STF-GHPA) and Multiple transcription factor-positive growth hormone-secreting adenomas (MTF-GHPA). The objective was to compare these two groups' clinical characteristics. Within the MTF-GHPA group, we further subtyped them based on transcription factors to evaluate potential variations in clinical manifestations. Logistic regression analyses were employed to develop a risk factor model for investigating factors influencing hormone remission.

Results: There were no statistically significant differences in terms of age, gender, serum GH, and IGF-1 levels between patients diagnosed with MTF-GHPA and STF-GHPA. However, patients with MTF-GHPA exhibited a higher proportion of hypopituitarism compared to those with STF-GHPA. Furthermore, MTF-GHPA were characterized by smaller tumor size and less invasiveness, as indicated by lower Knosp classes. However, patients with MTF-GHPA have a lower rate of hormonal remission (30.8%) and more postoperative complications (31.0%), which means that STF-GHPA (hormonal remission:71.6%; postoperative complications:13.4%) has a better endocrine outcome than MTF-GHPA patients. Between the PIT-1 + SF-1+ and PIT-1 + TPIT+ subtypes within MTF-GHPA, significant differences were also observed in tumor size, endocrine outcomes, and postoperative complications. Risk factors influencing hormonal remission for GHPA included preoperative GH level, primary/recurrent, extent of resection, and transcription factor expression.

Conclusion: Co-expression of multiple transcription factors is an important factor associated with clinical behavior and endocrine outcomes in patients with GHPA.