Endocrine最新文献

Objective: To analyze the degree of control based on classical glucometric parameters and Glycemia Risk Index (GRI) in real-life conditions in a cohort of patients with type 1 Diabetes Mellitus (DM) and Latent Autoimmune Diabetes in Adults (LADA) and to assess the factors that are associated with GRI.

Patients and methods: Cross-sectional study. 447 adult patients with type 1 DM and LADA users of Intermittent Continuous Glucose Monitoring (iCGM) with an adherence ≥ 70% were included. GRI was calculated with its Hypoglycemia (CHypo) and Hyperglycemia (CHyper) Components. Multivariate linear regression analysis was performed to evaluate the factors associated with GRI.

Results: Mean age 44.6 years (SD 13.7); 57.7% men; 83.9% type 1 DM; 16.1% LADA; time of evolution 20.6 years (SD 12.3). In patients with type 1 DM vs. LADA, differences were observed in relation to age [-11.1 years (SD 1.7)], age of onset [-21.9 years (DE 1.5)], time of evolution [11.7 years (DE 1.5)], treatment modality (p < 0.001), Time in Range (TIR) [-6.3% (SD 2.2)], Time Below Range (TBR) [1.9% (SD 0.6)], TBR level 1 (TBR1) [1.4% (SD 0.5)], Time Above Range (TAR) level 2 (TAR2) [4.7% (SD 1.3)], Coefficient of Variation (CV) [4.6% (SD 0.9)], GRI [11.3% (SD 2.8)], CHypo [1.3% (SD 0.5)] and CHyper [4.8% (SD 1.7)]. The variables that were independently associated with GRI were TIR (β = -1.34; CI 95% -1.43 to -1.25; p < 0.001), Glucose Management Indicator (GMI) (β = -5.82; CI 95% -7.59 to -4.05; p < 0.001), CV (β = 0.67; CI 95% 0.57 to 0.77; p < 0.001) and adherence to sensor usage (β = -0.16; CI 95% -1.27 to -0.06; p < 0.002).

Conclusions: LADA present better control according to some glucometric parameters and a low GRI. However, the type of DM is not a factor that is independently associated with GRI.

Purpose: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs).

Methods: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis.

Results: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49).

Conclusions: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Purpose: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults.

Methods: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted.

Results: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed.

Conclusions: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.

Purpose: To evaluate comprehensive bone health among young Indian women, including bone mass, microarchitecture, and turnover, in relation to their non-alcoholic fatty liver disease (NAFLD) status.

Methods: This cross-sectional study (May 2018-November 2019) recruited women with a history of gestational diabetes mellitus (GDM) and normoglycemia in their index pregnancy, who were at least 6 months postpartum. All participants underwent abdominal ultrasonography for determination of NAFLD status (grades 2 and 3: severe NAFLD) and transient elastography (FibroScan) for hepatic fibrosis (LSM >6 kPa). Bone mass was assessed by DXA, bone microarchitecture with trabecular bone score {TBS} (low TBS ≤ 1.310) and bone turnover with markers of bone formation (osteocalcin and P1NP), and resorption (CTX).

Results: Bone mineral density (BMD) at femoral neck (p = 0.026) and total hip (p = 0.007) was significantly higher among women with NAFLD (n = 170) compared to those without (n = 124). There was no significant difference in bone turnover markers between the two groups. The presence of NAFLD [adjusted OR: 1.82 (1.07, 3.11)] was associated with low TBS, with a greater strength of association among women with severe NAFLD [adjusted OR: 2.97 (1.12, 7.88)]. However, these associations were attenuated and no longer significant after additionally adjusting for BMI. Women with NAFLD and hepatic fibrosis manifested significantly higher BMD at lumbar spine, femoral neck, and total hip (p < 0.001 for all) and significantly lower bone turnover markers (osteocalcin, p = 0.009 and CTX, p = 0.029), however, the association with low TBS was not observed.

Conclusion: Among young Indian women, NAFLD is associated with increased bone mass and impaired bone microarchitecture, and hepatic fibrosis with increased bone mass and reduced bone turnover.

Purpose: Due to overdiagnosis, the incidence of thyroid cancer (TC) has increased in high-income countries, including Italy. Efforts have been made to address this issue since the mid-2010s, but more information is needed about how TC incidence has changed. We aim to examine the trend in TC incidence in the Lazio Region (central Italy) and assess the impact of the 2014 Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) to identify potential changes in TC diagnosis.

Methods: To identify TC cases, we conducted a population-based study (period 2007-2019) using the data from the Lazio Region Cancer Registry (5.8 million residents). We calculated the annual age-standardized incidence rates of TC for both sexes and analyzed the impact of ICCRTC on monthly incidence rates using segmented linear regression applied to interrupted time-series (ITS).

Results: Throughout the 13 years, there was a significant decline in TC annual incidence rates, more pronounced in females. Our results are consistent with reports from outside Europe (United States and South Korea). Following ICCRTC implementation in 2014, a step-change reduction in both sexes was revealed.

Conclusions: Our study indicates a significant decrease in the incidence of TC, particularly among females. The ITS analysis highlights the possible role of ICCRTC in reducing overdiagnosis. As the Lazio Region reflects the Italian population in terms of various demographic, health, and lifestyle indicators, our findings can be applicable at the national level.

Purpose: To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion.

Methods: The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed.

Results: In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3.

Conclusion: Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

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.

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.

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.

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.