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Open access

Olli Helminen, Tytti Pokka, Susanna Aspholm, Jorma Ilonen, Olli G Simell, Mikael Knip, and Riitta Veijola


Subtypes in type 1 diabetes pathogenesis have been implicated based on the first-appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.

Design and methods

Dysglycemic markers are defined as a 10% increase in HbA1c in a 3–12 months interval or HbA1c ≥5.9% (41 mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8 mmol/L. A primary autoantibody could be detected in 295 children who later developed at least 1 additional biochemical autoantibody. These children were divided into three groups: insulin autoantibody (IAA) multiple (n  = 143), GAD antibody (GADA) multiple (n  = 126) and islet antigen 2 antibody (IA-2A) multiple (n  = 26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped as IAA only (n  = 87), GADA only (n  = 114) and IA-2A only (n  = 28).


No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P < 0.001 between groups) and the highest random plasma glucose (P = 0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P = 0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P < 0.001) and 7% vs 43% (P < 0.001)), respectively.


The phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.

Open access

Zhiyan Yu, Yueyue Wu, Rui Zhang, Yue Li, Shufei Zang, and Jun Liu

Background: This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM)

Methods: 1243 patients with T2DM (NAFLD with coexistent T2DM, n = 760; T2DM with no NAFLD, n = 483) were analysed Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on 4 factors (FIB-4), were applied to evaluate NAFLD fibrosis risk.

Results: There was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group, or between males and females after adjusting for age, BMI, and gender. In postmenopausal women, there was an increased risk of osteoporosis (OR: 4.41, 95% confidence interval:1.04-18.70, P=0.039) in the FIB-4 high risk group compared with the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% confidence interval:1.40-25.60, P = 0.043) compared with the low risk group. Among men over 50, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group, and no significant difference in BMD and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk.

Conclusion: There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.

Open access

Ya Zhang, Xiaoqiu Chu, Yuling Liu, Yueting Zhao, Xue Han, Xin Hu, Pingping Xiang, Guofang Chen, Chao Liu, and Shuhang Xu

Objective: To compare the efficacy and safety of ethanol ablation (EA) and microwave ablation (MWA) in the treatment of cystic or predominantly cystic thyroid nodules.

Methods: Patients with cystic or predominantly cystic thyroid nodules intervened with EA or MWA were retrospectively enrolled and divided into EA group (n=30) and MWA group (n=31). The volume and volume reduction rate (VRR) of thyroid nodules before ablation, and at 3 months and 12 months after ablation were compared between the two groups. The effective rate (ER) and incidence of adverse events in both groups were recorded.

Results: The median VRR and ER at 3 months after ablation were significantly higher in EA group than in MWA group (81.30% vs. 75.76%, P=0.011; 76.67% [23/30] vs. 51.61% [16/31], P=0.040), while no significant difference was detected at 12 months (93.39% vs. 88.78%, P=0.141; 86.67% [26/30] vs. 87.10% [27/31], P=0.960). The median VRR of small nodules in EA group was significantly higher than that in MWA group (81.30% vs. 71.18%, P=0.006; 93.40% vs. 83.14%, P=0.032). There was no significant difference of median VRR of medium nodules at final follow-up between MWA and EA group (93.01% vs. 89.68%, P=0.482). Serious adverse events were not reported in both groups.

Conclusion: EA and MWA are both effective and safe in the treatment of cystic or predominantly cystic thyroid nodules. EA is more cost-effective and effective than MWA for small nodules, but it requires more cycles of treatment and may pose a higher risk of postoperative pain compared with MWA.

Open access

Yuntao Song, Jiaxin Wang, Yanli Zhu, Guohui Xu, Tianxiao Wang, and Bin Zhang

Objective: The central neck lymph node (LN) status is important for the treatment strategy of papillary thyroid cancer (PTC), while the diagnosis is difficult. This study aims to evaluate the diagnostic value of fine-needle aspiration (FNA) and its washout thyroglobulin (FNA-Tg) detection in central neck LN metastasis.

Methods: Central neck LNs with FNA cytology (FNA-C) and FNA-Tg measurements from a tertiary hospital were included. Tg levels were correlated with histopathological or follow-up results. The diagnostic performance of FNA-C, FNA-Tg, and combining FNA-C and FNA-Tg for detecting LN metastasis was assessed.

Results: A total of 132 LNs in the central neck from 129 patients were studied. The median FNA-Tg concentration of 74 metastatic LNs was 552.5 ng/mL. Whereas, in 58 benign LNs, the median Tg concentration was 0.1 ng/mL (P<0.001). Receiver operating characteristic (ROC) analysis (area under the curve, 0.861) was used, and a cutoff value of 14.6 ng/mL was obtained. There was no significant increase in the diagnostic accuracy when FNA-Tg was used or combined with FNA-C, compared with FNA-C alone. The size, location of LNs, the presence of the ipsilateral thyroid gland, and Hashimoto's thyroiditis (HT) did not affect the incidence of misdiagnosis.

Conclusions: FNA-C is the gold standard for evaluating central neck metastasis in PTC patients. Measurement of Tg levels in FNA washout does not improve the diagnostic accuracy any further.

Open access

Philippe Jean-Luc Gradidge, Nicole G Jaff, Shane A. Norris, Marketa Toman, and Nigel J Crowther

Gluteofemoral fat correlates negatively with a number of cardiometabolic disease risk factors but the mechanisms involved in these relationships are unknown. The aim of this study was to test the hypothesis that gluteofemoral fat attenuates the risk of cardiometabolic disease by increasing blood adiponectin levels. This was a cross sectional study in which arm, leg, gluteofemoral, abdominal subcutaneous and visceral fat levels were measured by dual-energy X-ray absorptiometry in 648 African females. Fasting serum adiponectin, lipid, insulin and plasma glucose levels and blood pressure were measured. Relationships between variables were analysed using multivariable linear regression and structural equation modelling. Adiponectin correlated positively (β=0.45, p<0.0001) with gluteofemoral fat in a multivariable regression model that included age, height and arm, subcutaneous and visceral fat levels. In further regression models, there was a negative correlation of gluteofemoral fat with fasting glucose (β=-0.28; p<0.0001) and triglyceride levels (β=-0.29; p<0.0001), and insulin resistance (HOMA; β=-0.26; p<0.0001). Structural equation modelling demonstrated that adiponectin mediated 20.7% (p<0.01) of the association of gluteofemoral fat with insulin resistance and 16.1% (p<0.01) of the association with triglyceride levels but only 6.67% (p=0.31) of the association with glucose levels. These results demonstrate that gluteofemoral and leg fat are positively associated with adiponectin levels, and that the negative association of lower body fat with insulin resistance and triglyceride levels may partially be mediated by this adipokine. Further studies are required to determine other factors that mediate the effect of lower body fat on cardiometabolic disease risk factors.

Open access

Wei Liu, Yunke Ma, Xiaoling Cai, Yu Zhu, Mingxia Zhang, Juan Li, Jing Chen, Dawei Shi, and Linong Ji

Objective: To explore the relationship between C-peptide secretion and time in range (TIR) in adult patients with type 1 diabetes.

Methods: From December 2018 to December 2020, 76 type 1 diabetes participants were enrolled from the Department of Endocrinology and Metabolism of Peking University People's Hospital. All participants wore intermittently scanned continuous glucose monitoring (isCGM), and insulin dosage were adjusted according to standardized clinical procedures. Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10-200 pmol/L) based on fasting serum C-peptide level. Differences of time in range (TIR), metrics related to glucose variability and hypoglycemic events were compared.

Results: A total of 94,846 isCGM values obtained from 39 male and 37 female participants were analyzed. Individuals with preserved C-peptide secretion had shorter diabetes duration [2.0 (0.5, 10.0) vs 10.0 (3.0, 18.3) years, P=0.002]. TIR was higher in the individuals with preserved C-peptide than those with decreased C-peptide [67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P<0.001], and time above range (TAR) was significantly lower in those with preserved C-peptide [28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P<0.001]. Preserved C-peptide was associated with lower glucose variability, as defined by standard deviation (SD) [3.0mmol/L (2.6, 3.4) vs 3.8mmol/L (3.2, 4.3), P<0.001] and interquartile range (IQR) [4.3mmol/L (3.1, 4.8) vs 5.3mmol/L (4.5, 6.3), P<0.001]. Metrics related to hypoglycemia were not different between the two groups.

Conclusion: Preserved C-peptide secretion was associated with higher TIR and lower glucose variability in Chinese type 1 diabetes adults.

Open access

Malgorzata Fuksiewicz, Maria Kowalska, Agnieszka Kolasinska-Cwikla, and Beata Kotowicz

The aim of this study was to assess the usefulness of neuron-specific enolase (NSE) concentrations as a prognostic factor in patients with neuroendocrine neoplasms and to determine the relationship between NSE and clinicopathological features. Serum NSE levels were measured in 179 NEN patients before treatment. It was found that NSE levels in patients with a primary pancreatic location were higher compared to patients with a small intestine lesion (P = 0.015). NSE levels were significantly higher in patients with primary pancreatic location with histological grade G2 compared with the group with low-grade G1 (P = 0.047). Patients with initial liver involvement showed significantly higher NSE levels compared to patients with tumour location in the pancreas (P = 0.009). Statistical analysis confirmed that higher NSE levels were associated with disease progression (P = 0.001) in both the overall study group and in patients with tumours in the pancreas and small intestine. During treatment monitoring, an increase in median NSE concentrations was observed in patients with persistent progression with subsequent blood draws, and a decrease in NSE concentrations was observed in patients with disease stabilisation. We showed that NSE concentrations have prognostic value for progression-free survival in addition to primary liver involvement. In conclusion, the most important results of the study include the demonstration of an association between NSE concentrations and clinical status, which confirms its usefulness in patient monitoring and as a potential predictive indicator for progression-free survival in patients with NENs.

Open access

Arnaud Lagarde, Gregory Mougel, Lucie Coppins, Magalie Haissaguerre, Lauriane Le Collen, Amira Mohamed, Marc Klein, Marie-Françoise Odou, Antoine Tabarin, Hedia Brixi, Thomas Cuny, Brigitte Delemer, Anne Barlier, and Pauline Romanet

Purpose: Mosaicism is a feature of several inherited tumor syndromes. Only few cases of mosaicism in Multiple Endocrine Neoplasia type 1 (MEN1) have been described. Next generation sequencing (NGS) offers new possibilities for detecting mosaicism. Here we report the first study to systematically look for MEN1 mosaicism, using blood DNA, in MEN1-suspected patients but without MEN1 pathogenic variants (PV) in a heterozygous state. Methods: digital targeted NGS, including unique molecular identifiers (UMIs), was performed in routine practice and the analytic performance of this method was verified. Results: Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allele frequencies ranged from 2.3 to 9.5%. The detection rate of MEN1 mosaicism in patients bearing at least 3 MEN1 lesions was 17% (3/18). No cases were detected in patients with 2 lesions. Conclusion: We report here 3 new cases with MEN1 mosaicism. This study examined the performance of UMI in the diagnosis of MEN1 mosaicism in routine practice and our results underline that the frequency of mosaicism is probably underestimated in patients with suspected MEN1.

Open access

Barbara J Boucher

High vitamin D deficiency rates, with rickets and osteomalacia, have been common in south Asians (SAs) arriving in Britain since the 1950s with preventable infant deaths from hypocalcaemic status-epilepticus and cardiomyopathy. Vitamin D deficiency increases common SA disorders (type 2 diabetes and cardiovascular disease), recent trials and non-linear Mendelian randomisation studies having shown deficiency to be causal for both disorders. Ethnic minority, obesity, diabetes and social deprivation are recognised COVID-19 risk factors but vitamin D deficiency isn’t, despite convincing mechanistic evidence of it. Adjusting analyses for obesity/ethnicity abolishes vitamin D deficiency in COVID-19 risk prediction but both factors lower serum 25(OH)D specifically. Social deprivation inadequately explains increased ethnic-minority COVID-19 risks. SA vitamin D deficiency remains uncorrected after 70 years, official bodies using ‘education’, ‘assimilation’ and ‘diet’ as ‘proxies’ for ethnic differences and increasing pressures to assimilate. Meanwhile, English rickets was abolished from ~1940 by free ‘welfare foods’ (meat, milk, eggs, cod-liver-oil), for all pregnant/nursing mothers and young children (<5 years old). Cod-liver-oil was withdrawn from antenatal clinics from 1994 (for excessive vitamin A teratogenicity), without alternative provision. The take-up of 2006 ‘Healthy-Start’ scheme food-vouchers for low-income families with young children (<3 years old) has been poor, being inaccessible and poorly publicized. COVID-19 pandemic advice for UK adults in ‘lockdown’ was ‘400 IU vitamin D/day’, inadequate for correcting the deficiency seen winter/summer at 17.5%/5.9% in White, 38.5%/30% in Black and 57.2%/50.8% in SA people in representative UK Biobank subjects when recruited ~14 years ago and remaining similar in 2018. Vitamin D inadequacy worsens many non-skeletal health risks. Not providing vitamin D for preventing SA rickets and osteomalacia continues to be unacceptable, as deficiency-related health risks increase ethnic health disparities, while abolishing vitamin D deficiency would be easier and more cost-effective than correcting any other factor worsening ethnic minority health in Britain