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Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. Methods 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. Results SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. Conclusions Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

Abstract Backgrounds Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. Methods This study was undertaken as a case–control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and

Diabetes is a disease of great and rising prevalence, with the obesity epidemic being a significant contributing risk factor. Duodenal–jejunal bypass liner (DJBL) is a reversible implant that mimics the effects of more aggressive surgical procedures, such as gastric bypass, to induce weight loss. We hypothesized that DJBL also influences the glucose dynamics in type II diabetes, based on the induced changes already demonstrated in other physiological characteristics and parameters. In order to assess the validity of this assumption, we conducted a quantitative analysis based on several nonlinear algorithms (Lempel–Ziv Complexity, Sample Entropy, Permutation Entropy, and modified Permutation Entropy), well suited to the characterization of biomedical time series. We applied them to glucose records drawn from two extreme cases available of DJBL implantation: before and after 10 months. The results confirmed the hypothesis and an accuracy of 86.4% was achieved with modified Permutation Entropy. Other metrics also yielded significant classification accuracy results, all above 70%, provided a suitable parameter configuration was chosen. With the Leave–One–Out method, the results were very similar, between 72% and 82% classification accuracy. There was also a decrease in entropy of glycaemia records during the time interval studied. These findings provide a solid foundation to assess how glucose metabolism may be influenced by DJBL implantation and opens a new line of research in this field.

This paper analyses the performance of SampEn and one of its derivatives, Fuzzy Entropy (FuzzyEn), in the context of artifacted blood glucose time series classification. This is a difficult and practically unexplored framework, where the availability of more sensitive and reliable measures could be of great clinical impact. Although the advent of new blood glucose monitoring technologies may reduce the incidence of the problems stated above, incorrect device or sensor manipulation, patient adherence, sensor detachment, time constraints, adoption barriers or affordability can still result in relatively short and artifacted records, as the ones analyzed in this paper or in other similar works. This study is aimed at characterizing the changes induced by such artifacts, enabling the arrangement of countermeasures in advance when possible. Despite the presence of these disturbances, results demonstrate that SampEn and FuzzyEn are sufficiently robust to achieve a significant classification performance, using records obtained from patients with duodenal-jejunal exclusion. The classification results, in terms of area under the ROC of up to 0.9, with several tests yielding AUC values also greater than 0.8, and in terms of a leave-one-out average classification accuracy of 80%, confirm the potential of these measures in this context despite the presence of artifacts, with SampEn having slightly better performance than FuzzyEn.

Abstract Background Maternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls. Methods In this prospective, longitudinal case-control study — including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women — fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors — including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) — were analyzed across three time periods: the last menstrual period to 13 (V1), 14–22 (V2), and 23–32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed. Results At 28–32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18–22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28–32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester. Conclusion In women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

BackgroundThis paper describes the development of a mobile app for diabetes mellitus (DM) control and self-management and presents the results of long-term usage of this system in the Czech Republic. DM is a chronic disease affecting large numbers of people worldwide, and this number is continuously increasing. There is massive potential to increase adherence to self-management of DM with the use of smartphones and digital therapeutics interventions. ObjectiveThis study aims to describe the process of development of a mobile app, called Mobiab, for DM management and to investigate how individual features are used and how the whole system benefits its long-term users. Using at least 1 year of daily records from users, we analyzed the impact of the app on self-management of DM. MethodsWe have developed a mobile app that serves as an alternative form to the classic paper-based protocol or diary. The development was based on cooperation with both clinicians and people with DM. The app consists of independent individual modules. Therefore, the user has the possibility to use only selected features that they find useful. Mobiab was available free of charge on Google Play Store from mid-2014 until 2019. No targeted recruitment was performed to attract users. ResultsMore than 500 users from the Czech Republic downloaded and signed up for the mobile app. Approximately 80% of the users used Mobiab for less than 1 week. The rest of the users used it for a longer time and 8 of the users produced data that were suitable for long-term analysis. Additionally, one of the 8 users provided their medical records, which were compared with the gathered data, and the improvements in their glucose levels and overall metabolic stability were consistent with the way in which the mobile app was used. ConclusionsThe results of this study showed that the usability of a DM-centered self-management smartphone mobile app and server-based systems could be satisfactory and promising. Nonetheless, some better ways of motivating people with diabetes toward participation in self-management are needed. Further studies involving a larger number of participants are warranted to assess the effect on long-term diabetes management.

Background: Brown adipose tissue (BAT) is a therapeutic target to combat obesity and related disorders. Pheochromocytoma and functional paraganglioma (PPGL) are associated with activated BAT due to catecholamine excess. Our aim was to evaluate BAT activity by gene profile and assess its relation to clinical characteristics and overproduced catecholamine. Methods: mRNA expression of 15 genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was measured via RT-PCR in 25 patients with PPGL and 14 controls undergoing cholecystectomy. Results: We found in VAT of PPGL higher expression of UCP1 (p < 0.001), CEBPB, PPARGC1A (both p < 0.001), PRDM16 (p = 0.069) and DIO2 (p = 0.005). UCP1 expression correlated only with norepinephrine levels and its metabolite. UCP1 expression, among others, correlated negatively with BMI, age and positively with HDLc levels. Dominance of BAT or BeAT markers was not assessed in PPGL. In SAT of PPGL, we found higher expression of ADRB3, CIDEA (both p < 0.05), and PPARGC1A (p = 0.001), but not UCP1. Conclusion: We demonstrate signs of UCP1-dependent norepinephrine-induced thermogenesis connected with higher expression of DIO2, PPARGC1A, CEBPB and PRDM16 in retroperitoneal VAT of PPGL and its relations to circulating HDLc and triglycerides levels. However, no direct relationship with increased basal energy metabolism measured by calorimetry was found.

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n=12) and without (non-T2DM, n=17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6±0.7 vs. 5.8±0.2 mmol/l, p

Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24±7.45 vs. 11.22±1.34%, p=0.025) with a similar trend observed in non-CAD subjects (29.68±7.61 vs. 10.13±2.01%, p=0.067). T (CD3+) cells were increased (75.33±2.18 vs. 65.24±4.49%, p=0.032) and CD3- cells decreased (21.17±2.26 vs. 31.64±4.40%, p=0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22±2.43 vs. 0.96±0.21%, p=0.039 for CAD and 12.49±5.83 vs. 1.16±0.19%, p=0.016 for non-CAD) and reduced natural killer (NK) cells (5.96±1.32 vs. 13.22±2.10%, p=0.012 for CAD and 5.32±1.97 vs. 13.81±2.72%, p=0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.

The relationship between Hashimoto’s thyroiditis (HT) and thyroid cancer (TC) is a controversial topic; it remains unclear if HT acts as a risk factor of TC. The aim of our study was to compare the presence of HT and thyroid function in patients with TC and benign nodules. We analyzed 2571 patients after fine needle aspiration biopsy of thyroid nodule. Totally, 91 patients with primary TC and 182 sex- and age-matched controls were included. Positive antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies were associated with TC (anti-TPO 44% in TC vs. 27% in controls, P=0.005, anti-TG 35% in TC group vs. 21% in controls, P=0.018), and the TC group had significantly higher TSH (median 1.88 mIU/l vs. 1.21 mIU/l, P