Delphi-Based Consensus on Treatment Intensification in Type 2 Diabetes Subjects Failing Basal Insulin Supported Oral Treatment: Focus on Basal Insulin + GLP-1 Receptor Agonist Combination Therapies

Introduction: The aim of this study was to elaborate a consensus on treatment intensification strategies in patients with type 2 diabetes failing basal insulin supported oral therapy (BOT). The panel focused on glucagon-like peptide-1 receptor agonists (GLP-1RA) and basal insulin (BI) combinations. Methods: The authors developed a Delphi questionnaire organized into ten statements and 77 items that focused on: the definition of BOT and BOT failure, intensification strategies, fixed-dose combinations in general and the BI/GLP-1RA fixed combination. The survey was administered in two rounds to a panel of 80 Italian diabetes specialists, who rated their level of agreement with each item on a 5-point Likert scale. Consensus was predefined as > 66% of the panel agreeing/disagreeing on any given item. Results: Consensus was achieved for 71 of the 77 items. The panel agreed that the use of sulfonylureas in the BOT regimen is inappropriate. BOT failure was defined as individualized targets not being met for glycated hemoglobin, fasting plasma glucose and/or postprandial plasma glucose. There was agreement that postprandial hyperglycaemia and/or presence of nocturnal hypoglycaemia or weight gain define BOT failure. Addition of a GLP-1RA to BI therapy was considered to be the best option for BOT intensification. There was consensus for the use of BI/GLP-1RA fixed combinations as valuable options to increase compliance and safely improve glycaemic control. The panel agreed in considering the fixed-ratio combination insulin degludec/liraglutide (IDegLira) to be preferable to the fixed-ratio combination insulin glargine/lixisenatide (iGlarLixi) in the control of glycaemia, body weight and cardiovascular risk. Conclusion: According to this Delphi consensus, the addition of a GLP-1RA may be the best option to intensify BOT. The BI/GLP-1RA fixed combinations may increase compliance and optimize the advantages of each of these molecules

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates

Use and effectiveness of dapagliflozin in routine clinical practice. An Italian multicenter retrospective study

In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination. At baseline, patients starting dapagliflozin were younger, had a longer disease duration, higher HbA1c, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin was changing during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLM were also within the expected range based on RCTs. This real-world study demonstrates an initial channelling of dapagliflozin to difficult-to-treat patients. Nonetheless, dapagliflozin provided significant benefits on glucose control, body weight, and blood pressure that were in line with findings from RCTs

Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

Within the complex pathological picture associated to diabetes, high glucose (HG) has ". per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG. © 2014 Elsevier Inc

Plasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control

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Policaptil Gel Retard® reduces body weight and improves insulin sensitivity in obese subjects

Policaptil Gel Retard® (PGR), a natural fiber-based molecule, has been shown to prevent weight gain and ameliorate insulin-resistance indices in obese children and adolescents. The aim of this study was to compare the effects of 12 weeks of low calories and low glycemic index (LC-LGI) diet associated or not with the intake of PGR on anthropometric, bioimpedance, and metabolic parameters. Data from 20 obese adult subjects (10 per group) were analyzed. An LC-LGI diet with or without PGR intake reduced weight, BMI, and waist circumference. PGR intake elicited a reduction in fasting plasma insulin and insulin resistance index together with an improvement in insulin sensitivity

TELERETINOGRAPHY INTO DIABETES INTEGRATED CARE: AN ITALIAN EXPERIENCE

Integrated care allows information exchange among health professionals. In diabetes, a better control of outcomes and a reduction of the need for hospital admission were noticed worldwide. Teleretinography, performed in Diabetology Units (DUs), graded by a remote ophthalmologist, and forwarded to general practitioners (GPs), can cost-effectively identify retinal microangiopathy. In our DU, participating in a national diabetes integrated care program (IGEA), in a ten-month period teleretinography was performed in 362 new patients not having undergone fundus examination in the last year or more. Retinal imaging allowed discovering stages of diabetic retinopathy (DR) to be referred to the hospital setting, and a series of comorbidities. The suggested care path and follow-up were rapidly forwarded to GPs for all patients, thus improving their adherence to guidelines. These advantages and other important ones, such as reducing fundus examinations in ophthalmic settings and conveying information into the patient's Electronic Health Record, make teleretinography worth becoming part of the integrated care process in diabetic patients.   

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Background: Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. Methods: We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. Results: At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. Conclusions: In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446.)Sin financiación72.406 JCR (2016) Q1, 1/155 Medicine, General & InternalUE

LDL-cholesterol control in the primary prevention of cardiovascular diseases. An expert opinion for clinicians and health professionals

Aims: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. Data synthesis: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. Conclusions: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk