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Open access

Sahar Hossam El Hini, Yehia Zakaria Mahmoud, Ahmed Abdelfadel Saedii, Sayed Shehata Mahmoud, Mohamed Ahmed Amin, Shereen Riad Mahmoud, and Ragaa Abdelshaheed Matta

Objective

Angiopoietin-like proteins (ANGPTL) 3, 4 and 8 are upcoming cardiovascular biomarkers. Experimental studies showed that thyroid hormones altered their levels. We assessed ANGPTL3, 4 and 8 as predictors of cardiovascular functions among naïve subclinical and naïve overt hypothyroidism (SCH and OH) and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function.

Design and methods

The study was a prospective follow-up study that assessed ANGPTL3, 4 and 8 levels, vascular status (flow-mediated dilation% of brachial artery (FMD%), carotid intima-media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), and LV mass), well-known cardiovascular risk factors and homeostatic model for the assessment of insulin resistance, at two time points, that is, among naïve SCH, naïve OH, and healthy subjects groups; and at 6 months after achieving the euthyroid state with LT4 by calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4-hypothyroid groups.

Results

Significantly elevated levels of ANGPTL3, 4 and 8 among hypothyroid groups than the healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL level included ANGPTL3 and 4 for impaired FMD%, and ANGPTL8 for LV mass among naïve SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve OH; ∆↓ANGPTL3 for ∆↓ASI meanwhile ∆↑freeT4 for ∆↓ANGPTL3, ∆↓fasting glucose, ∆↓triglyceride, and ∆↓thyroid peroxidase antibody for ∆↓ANGPTL4 among LT4-SCH. ∆↓ANGPTL4 for ∆↓MPI and ∆↓LV mass, meanwhile ∆↓TSH and ∆↓triglyceride for ∆↓ANGPTL3, ∆↑free T3 and ∆↓HOMA-IR for ∆↓ANGPTL4, and systolic blood pressure and waist circumference for ∆↓ANGPTL8 among LT4-OH.

Conclusion

Elevated ANGPTL3, 4 and 8 levels are differentially independent predictors of endothelial and cardiac function and are reduced with LT4 in SCH and OH.

Open access

Mahmoud Al-Masri, Tawfiq Al-Shobaki, Hani Al-Najjar, Rafal Iskanderian, Enas Younis, Niveen Abdallah, Abdelghani Tbakhi, Hussam Haddad, Mohammad Al-Masri, Zeinab Obeid, and Awad Jarrar

Purpose

This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center.

Methods

Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected.

Results

A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940).

Conclusion

BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Open access

Jan Kvasnička, Ondřej Petrák, Tomáš Zelinka, Judita Klímová, Barbora Kološov, Květoslav Novák, David Michalský, Jiří Widimský Jr, and Robert Holaj

Background

Pheochromocytomas (PHEO) are tumours with the ability to produce, metabolize and secrete catecholamines. Catecholamines overproduction leads to the decrease of longitudinal function of the left ventricle (LV) measured by speckle-tracking echocardiography. Patients with PHEO have a lower magnitude of global longitudinal strain (GLS) than patients with essential hypertension. GLS normalization is expected after resolution of catecholamine overproduction.

Methods

Twenty-four patients (14 females and 10 males) with a recent diagnosis of PHEO have been examined before and 1 year after adrenalectomy. An echocardiographic examination including speckle-tracking analysis with the evaluation of GLS and regional longitudinal strain (LS) in defined groups of LV segments (basal, mid-ventricular and apical) was performed.

Results

One year after adrenalectomy, the magnitude of GLS increased (−14.3 ± 1.8 to −17.7 ± 1.6%; P < 0.001). When evaluating the regional LS, the most significant increase in the differences was evident in the apical segment compared to mid-ventricular and basal segments of LV (−5.4 ± 5.0 vs −1.9 ± 2.7 vs −1.6 ± 3.8; P < 0.01).

Conclusions

In patients with PHEO, adrenalectomy leads to an improvement of subclinical LV dysfunction represented by the increasing magnitude of GLS, which is the most noticeable in apical segments of LV.

Open access

Sneha Arya, Sandeep Kumar, Anurag R Lila, Vijaya Sarathi, Saba Samad Memon, Rohit Barnabas, Hemangini Thakkar, Virendra A Patil, Nalini S Shah, and Tushar R Bandgar

Objective

The literature regarding gonadoblastoma risk in exonic Wilms’ tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian–Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma.

Design

Combined retrospective–prospective analysis.

Methods

In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patients and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants.

Results

The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms’ tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing teratoma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases).

Conclusions

WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

Open access

Yuerong Yan, Lili You, Xiaoyi Wang, Zhuo Zhang, Feng Li, Hongshi Wu, Muchao Wu, Jin Zhang, Jiayun Wu, Caixia Chen, Xiaohui Li, Biwen Xia, Mingtong Xu, and Li Yan

Objectives

A variety of factors differed between rural and urban areas may further influence iodine status and thyroid structure. Hence, this study compared iodine nutrition, the prevalence of thyroid goiter, and nodules between rural and urban residents in Guangzhou, a southern coastal city of China.

Methods

A total of 1211 rural residents and 1305 urban residents were enrolled in this cross-sectional study. A questionnaire regarding personal characteristics was administered. Urinary iodine concentration (UIC) was examined. Ultrasonography of the thyroid was performed to evaluate thyroid goiter and nodules. Multiple logistic analysis was used to identify the potential associated factors.

Results

The median UIC was significantly lower in rural residents than in urban residents (120.80 μg/L vs 136.00 μg/L, P < 0.001). Although the coverage rate of iodized salt was much higher in rural residents than in urban residents (99.59% vs 97.29%, P < 0.001), the percentages of seafood intake (8.60% vs 29.29%, P < 0.001), iodine-containing drug consumption (0.33% vs 1.24%, P = 0.011), and iodine contrast medium injection (0.58% vs 1.87%, P = 0.004) were lower in rural residents than in urban residents. Both the prevalence of thyroid goiters and nodules was significantly higher in rural residents than in urban residents (goiter: 8.06% vs 1.20%, P < 0.001; nodules: 61.89% vs 55.04%, P = 0.023). Living in rural areas was associated with thyroid goiter (OR 5.114, 95% CI 2.893–9.040, P < 0.001).

Conclusions

There were differences in iodine nutrition and the prevalence of thyroid goiter and nodules in rural and urban residents in Guangzhou. Differentiated and specialized monitoring is recommended in our area.

Open access

Rui Zhang, Xinmei Huang, Yue Li, Zhiyan Yu, Yueyue Wu, Bingbing Zha, Heyuan Ding, Shufei Zang, and Jun Liu

Objective

The aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes.

Methods

A cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups (n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels.

Results

The mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140–352) vs 203.5 (130.5–312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03–1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels.

Conclusion

T2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.

Open access

Jun-Xin Yan, Bin-Jing Pan, Ping-Ping Zhao, Li-Ting Wang, Jing-Fang Liu, and Song-Bo Fu

Objective

Previous studies have shown the correlations between serum ferritin and non-alcoholic fatty liver disease (NAFLD) or diabetes. However, this relationship remains unclear in patients with type 2 diabetes (T2DM) with NAFLD. Therefore, this study aimed to elaborate the relationship between serum ferritin levels and NAFLD in middle-aged and older patients with T2DM and further explored the biomarkers for NAFLD in T2DM.

Methods

A total of 805 middle-aged and older patients with T2DM were divided into NAFLD and non-NAFLD groups, and their serum ferritin levels were compared. Next, NAFLD group were divided into five subgroups according to the quintile levels of serum ferritin, and the differences in the constituent ratios of NAFLD were analyzed. A logistic regression analysis was performed to determine the risk factors for NAFLD in patients with T2DM.

Results

The serum ferritin levels were significantly higher in T2DM patients with NAFLD (168.47 (103.78, 248.00) ng/mL) than in the non-NAFLD patients (121.19 (76.97, 208.39) ng/mL). The constituent ratios of NAFLD were significantly higher in the F5 and F4 groups than in the F2 or F1 groups (22.70 and 22.70% vs. 15.90 and 16.90%, respectively; P < 0.05). Binary logistic regression analysis showed that serum ferritin (P = 0.001) was an independent risk factor for NAFLD in patients with T2DM.

Conclusions

Serum ferritin levels were significantly increased in T2DM with NAFLD, and the constituent ratios of NAFLD increased gradually along with the increased levels of serum ferritin. Thus, serum ferritin is an independent risk factor for NAFLD in patients with T2DM.

Open access

Xiying Zeng, Yinxiang Huang, Mulin Zhang, Chen Yun, Ye Jiawen, Yan Han, Ma Danyan, Xin Zheng, Xiaohong Yan, and Changqin Liu

Objective: Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).

Methods: In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson's correlation and multivariable logistic regression analyses were performed to determine associations of AMH with central obesity and general obesity.

Results: Subjects with the increasing of body mass index (BMI) showed significantly lower values of AMH (median (IQR) 8.95 (6.03-13.60) ng/mL in normal weight group, 6.57 (4.18-8.77) ng/mL in overweight group, and 6.03 (4.34-9.44) ng/mL in obesity group, respectively, p=0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and obesity indices (WC, hip circumferences, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and Chinese visceral adiposity index (CVAI)) respectively. Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56(5.29-12.96) vs. 6.22(4.33-8.82) ng/mL; p=0.003). Pearson’s correlation analysis showed that AMH were significantly and negatively correlated with BMI (r=-0.280; p<0.001), WC (r=-0.263; p<0.001), WHtR (r=-0.273; p<0.001), and CVAI (r=-0.211; p=0.006) respectively. Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity, but was not significantly associated with general obesity.

Conclusions: AMH was independently and negatively associated with central obesity. Closely monitoring WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

Open access

Xue-Lian Zhang, Xinyi Zhao, Yong Wu, Wen-qing Huang, Jun-jiang Chen, Peijie Hu, Wei Liu, Yi-Wen Chen, Jin Hao, Rong-Rong Xie, Hsiao Chang Chan, Ye Chun Ruan, Hui Chen, and Jinghui Guo

Objective: The beneficial effect of angiotensin(1–7), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how angiotensin(1–7) or MAS-1 affects insulin secretion remains elusive and whether endogenous level of angiotensin(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of CFTR, a cAMP-activated Cl- channel, in regulation of insulin secretion. Here, we tested possible involvement of CFTR in mediating angiotensin(1–7)’s effect on insulin secretion and measured the level of angiotensin(1–7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes.

Methods: Angiotensin(1–7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, western blotting as well as insulin ELISA in a pancreatic β cell line, RINm5F. Human blood samples were collected from 333 individuals with (n=197) and without (n=136) type 2 diabetes. Angiotensin(1–7), MAS-1 and CFTR level in the human blood were determined by ELISA.

Results: In RINm5F cells, angiotensin(1–7) induced intracellular cAMP increase, CREB activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not angiotensin(1–7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2-diabetic but not non-diabetic subjects.

Conclusion: These results suggested MAS-1 and CFTR as key players in mediating angiotensin(1–7)-promoted insulin secretion in pancreatic β cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

Open access

Xun Gong, Lili You, Feng Li, Qingyu Chen, Chaogang Chen, Xiaoyun Zhang, Xiuwei Zhang, Wenting Xuan, Kan Sun, Guojuan Lao, Chuan Wang, Yan Li, Mingtong Xu, Meng Ren, and Li Yan

Objective

Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes.

Methods

A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose–lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis.

Results

Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20–0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02–0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761).

Conclusions

Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.