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

A critical evaluation of Kenyon’s Shag (Phalacrocorax [Stictocarbo] kenyoni)

We examine the validity of Phalacrocorax [Stictocarbo] kenyoni, which was described by Siegel-Causey (1991) from the Aleutian Islands using midden remains and existing skeletal specimens. We emphasize a morphometric evaluation of the taxon using 224 skeletal specimens of North Pacific cormorants, but we also evaluate the qualitative characters originally used to characterize P. kenyoni. Principal components and discriminant function analyses of 14 skeletal characters failed to support the validity of the species. Similarly, all seven of the character states that Seigel-Causey described as unique to P. kenyoni also were found in P. pelagicus and P. urile. Thus, the three type specimens of P. kenyoni appear to be P. pelagicus. Although we could not confirm the validity of P. kenyoni, our morphometric analyses revealed that P. pelagicus individuals from the central Aleutians are smaller than those from surrounding populations

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

Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions

Cardiomyopathy associated with diabetes. the central role of the cardiomyocyte

The term diabetic cardiomyopathy (DCM) labels an abnormal cardiac structure and performance due to intrinsic heart muscle malfunction, independently of other vascular co-morbidity. DCM, accounting for 50%-80% of deaths in diabetic patients, represents a worldwide problem for human health and related economics. Optimal glycemic control is not sufficient to prevent DCM, which derives from heart remodeling and geometrical changes, with both consequences of critical events initially occurring at the cardiomyocyte level. Cardiac cells, under hyperglycemia, very early undergo metabolic abnormalities and contribute to T helper (Th)-driven inflammatory perturbation, behaving as immunoactive units capable of releasing critical biomediators, such as cytokines and chemokines. This paper aims to focus onto the role of cardiomyocytes, no longer considered as "passive" targets but as "active" units participating in the inflammatory dialogue between local and systemic counterparts underlying DCM development and maintenance. Some of the main biomolecular/metabolic/inflammatory processes triggered within cardiac cells by high glucose are overviewed; particular attention is addressed to early inflammatory cytokines and chemokines, representing potential therapeutic targets for a prompt early intervention when no signs or symptoms of DCM are manifesting yet. DCM clinical management still represents a challenge and further translational investigations, including studies at female/male cell level, are warranted

MicroRNA modulation by dietary supplements in obesity

The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities, contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity