COVID-19: is there a link between the course of infection and pharmacological agents in diabetes?

The Coronavirus disease 2019 (COVID-19) and type 2 diabetes (T2D) are two pandemics that share the dramatic impact on global mortality and economic resources. COVID-19 largely exhibits mild to moderate clinical manifestations. However, severe pneumonia with high fatality rate may occur, especially in the elderly and in patients with underlying conditions, such as diabetes and cardiovascular disease. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) binds to the angiotensin-converting enzyme 2 (ACE2), a ubiquitous trans-membrane carboxypeptidase, to enter the cells

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level

Bisphenol A and phthalates in diet: an emerging link with pregnancy complications

Endocrine-disrupting chemicals (EDCs) are exogenous substances that are able to interfere with hormone action, likely contributing to the development of several endocrine and metabolic diseases. Among them, Bisphenol A (BPA) and phthalates contaminate food and water and have been largely studied as obesogenic agents. They might contribute to weight gain, insulin resistance and pancreatic β-cell dysfunction in pregnancy, potentially playing a role in the development of pregnancy complications, such as gestational diabetes mellitus (GDM), and adverse outcomes. Pregnancy and childhood are sensitive windows of susceptibility, and, although with not univocal results, preclinical and clinical studies have suggested that exposure to BPA and phthalates at these stages of life might have an impact on the development of metabolic diseases even many years later. The molecular mechanisms underlying this association are largely unknown, but adipocyte and pancreatic β-cell dysfunction are suspected to be involved. Remarkably, transgenerational damage has been observed, which might be explained by epigenetic changes. Further research is needed to address knowledge gaps and to provide preventive measure to limit health risks connected with exposure to EDCs

High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes

Purpose: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. Methods: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. Results: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9–31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. Conclusions: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile

Deep Multi-Segmentation Approach for the Joint Classification and Segmentation of the Retinal Arterial and Venous Trees in Color Fundus Images

Presented at the 4th XoveTIC Conference, A Coruña, Spain, 7–8 October 2021.[Abstract] The analysis of the retinal vasculature represents a crucial stage in the diagnosis of several diseases. An exhaustive analysis involves segmenting the retinal vessels and classifying them into veins and arteries. In this work, we present an accurate approach, based on deep neural networks, for the joint segmentation and classification of the retinal veins and arteries from color fundus images. The presented approach decomposes this joint task into three related subtasks: the segmentation of arteries, veins and the whole vascular tree. The experiments performed show that our method achieves competitive results in the discrimination of arteries and veins, while clearly enhancing the segmentation of the different structures. Moreover, unlike other approaches, our method allows for the straightforward detection of vessel crossings, and preserves the continuity of the arterial and venous vascular trees at these locations.This work was funded by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Axencia Galega de Innovación (GAIN), Xunta de Galicia, ref. IN845D 2020/38; Xunta de Galicia and European Social Fund (ESF) of the EU through the predoctoral grant contracts ED481A-2017/328 and ED481A 2021/140; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, is funded by Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; IN845D 2020/38Xunta de Galicia; ED481A-2017/328Xunta de Galicia; ED481A 2021/140Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Comparative Effectiveness of DPP-4 Inhibitors Versus Sulfonylurea for the Treatment of Type 2 Diabetes in Routine Clinical Practice: A Retrospective Multicenter Real-World Study

Introduction: DPP-4 inhibitors (DPP4i) and sulfonylureas are popular second-line therapies for type 2 diabetes (T2D), but there is a paucity of real-world studies comparing their effectiveness in routine clinical practice. Methods: This was a multicenter retrospective study on diabetes outpatient clinics comparing the effectiveness of DPP4i versus gliclazide extended release. The primary endpoint was change from baseline in HbA1c. Secondary endpoints were changes in fasting plasma glucose, body weight, and systolic blood pressure. Automated software extracted data from the same clinical electronic chart system at all centers. Propensity score matching (PSM) was used to generate comparable cohorts to perform outcome analysis. Results: We included data on 2410 patients starting DPP4i and 1590 patients starting gliclazide (mainly 30–60 mg/day). At baseline, the two groups differed in disease duration, body weight, blood pressure, HbA1c, fasting glucose, HDL cholesterol, triglycerides, liver enzymes, eGFR, prevalence of microangiopathy, and use of metformin. Among DPP4i molecules, no difference in glycemic effectiveness was detected. In matched cohorts (n = 1316/group), patients starting DPP4i, as compared with patients starting gliclazide, experienced greater reductions in HbA1c (− 0.6% versus − 0.4%; p < 0.001), fasting glucose (− 14.1 mg/dl versus − 8.8 mg/dl; p = 0.007), and body weight (− 0.4 kg versus − 0.1 kg; p = 0.006) after an average 6 months follow-up. DPP4i improved glucose control more than gliclazide, especially in patients who had failed with other glucose-lowering medications or were on basal insulin. Conclusions: This large retrospective real-world study shows that, in routine clinical practice, starting a DPP4i allows better glycemic control than starting low-dose gliclazide. Funding: The Italian Diabetes Society, with external support from AstraZeneca

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies

Background: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. Aim: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. Results: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. Conclusions: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity

Humanities in the undergraduate medical and midwifery curriculum: a descriptive Italian comparative study.

There is an increasing emphasis on humanized care in obstetric and midwifery practice. The goal of this paper is to investigate if and how medical humanities content was present in the undergraduate medical syllabus and how similar or different this is from the undergraduate midwifery program in Italy. A review of the 2017-18 curriculum for Italian Schools of Medicine and of Midwifery was carried out through institutional websites or mailing requests. The following details were collected for each program: the type of humanities content; the academic credits allocated, whether it was taught as a stand-alone (independent) topic or not, and the year(s) of the program when it was provided. Programs were included for 39 Schools of Medicine and 36 Schools of Midwifery. All midwifery schools included at least one subject with humanities content. Five medical schools (12.9) did not appear to have any subjects in this area. Psychology and ethics/bioethics were the most frequently found topics in both disciplines, but, apart from history of medicine, midwifery was much more likely than medicine to include other humanities topics, and especially pedagogy, anthropology, sociology and communication studies, philosophy and cross-cultural studies were rarely or never included in either discipline. A greater breadth of humanities studies was included in midwifery schools. However, their relative importance appears to be low, given the low level of academic credits and lack of presence as independent subjects