Search

In the pandemic “Corona Virus Disease 2019” (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.

EDEN ISS is an H2020 project aimed at testing key technologies for plant cultivation in large-scale closed environments for a future implementation in space habitats. In this light, a Future Exploration Greenhouse has been designed, developed and deployed at the highly isolated German Neumayer III Antarctic Station to simulate the harsh conditions of an extra planetary outpost mission and test a typical space operation scenario. The greenhouse has been equipped with all the systems to control the environmental parameters (temperature, relative humidity, light intensity, etc.), and to accommodate and feed the plants during their lifecycle. A camera system has been implemented for plant status assessment via remote image analysis. A command and data handling system provides the capability to configure the experimental set points via software, and can be controlled by remote operators. A Mission Control Centre has been realized at DLR for remote monitoring and control of the facility. The MCC receives all the telemetry and the images and can make them available to other centres, which have been included in the operations loop to provide expert support to the on-site operator. This paper describes the facility and its capabilities as platform for fresh food production experiments in an extreme environment. It is an extended version of a paper presented at the AIDAA Congress 2019, in the Technical Session “Red Planet Exploration”.

People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2–infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.

The literature on ‘mountain mysticism’ includes a wide array of interpretations: Reductively, mystical states experienced on mountains may be viewed as neurological or psychological epiphenomena. A...

Additional file 1. Additional figures and tables.

Cardiovascular diabetology 21, 50 (2022). doi:10.1186/s12933-022-01481-0, Published by BioMed Central, London

MILD combustion has a wide potential in enhancing thermal efficiency with nearly zero emissions. It has no visible flame since the radiation from the reacting zones is attenuated due to both the intermediate species at reduced temperatures, induced by intensely burned gas recirculation, and the absence of particulate emitters. Beyond these main features, there are other characteristics such as temperature uniformity and distributed ignition that have to be addressed and analyzed looking at the peculiar role of the heat transfer for such reactors. First, the category of combustion systems object of the study is described. Afterwards an analysis on the heat transfer mechanisms under MILD combustion of gaseous fuels is carried out. Therefore, in this Mini-Review, several literature findings highlighting the role of the heat transfer on the combustion peculiarities of MILD reactors (i.e., temperature uniformity, distributed ignition, low pollutant emissions) are reported and discussed. Heat exchange modes, in fact, contribute to providing MILD macroscopic characteristics by means of the strong interplay between wall and gas heat transfer, instead of the reactive structure. In particular, the thermal behavior of these systems is analyzed in order to stress the distinctive role of the heat loss and the relative contributions of the convective and radiative terms. Heat transfer mechanisms between gas and walls and their interactions, in fact, favor the wide temperature distribution within the chamber. In order to better understand the different effects of the heat transfer under MILD regime, the mechanisms regarding walls and recirculating gas are separately investigated.

The aim of this meta-analysis was to investigate the impact of rapid-acting insulin analogues (RAIAs) and regular human insulin (RHI) on glycemic control, including long- and short-term glycemic variability as measured by glycated haemoglobin (HbA1c) and pre- and postprandial glucose (PPG).PubMed was searched for studies published between 1999 and 29 June 2016. Randomised controlled trials of patients with diabetes that assessed the effects of RAIAs or RHI on glycemic control, focusing on preprandial glucose, PPG and HbA1c, were included. Only studies that reported both means and standard deviations for those outcomes were analysed; from these data, weighted mean differences and 95% confidence intervals were generated to yield overall point estimates. The primary outcomes of the meta-analysis were the mean differences between RAIAs and RHI at the end of the study in PPG, preprandial glucose, and HbA1c.Twenty-seven studies (n = 7452) were included. The difference in PPG between RAIA- and RHI-treated patients was significant-in favour of RAIAs-in patients with type 1 diabetes (T1D) [- 22.2 mg/dL; 95% confidence interval (CI) - 27.4, - 17.0 mg/dL; P 0.0001] but not in those with type 2 diabetes (T2D). For preprandial glucose, there was a non-significant trend favouring RHIs in T1D; no data were available for patients with T2D. In patients with T1D, the between-group difference in end-of-treatment (EOT) HbA1c favoured RAIAs (- 0.13%; 95% CI - 0.18, - 0.08%; P 0.0001), but was not significant in patients with T2D. The main study limitations were the small number and heterogeneity of the included studies.These results demonstrate that RAIAs are more effective at reducing PPG and improving HbA1c than RHIs in T1D. More data are required to assess the effect of these agents on glucose control in T2D. In patients with diabetes, the risk of complications is increased by poor control of blood glucose levels and high blood glucose variability. Complications may include cardiovascular disease, eye problems and amputation. Control and variability of blood glucose levels can be evaluated using a range of measures, including (i) glycated haemoglobin (HbA1c) level at the end of the treatment period; (ii) change in HbA1c level during the treatment period; (iii) fasting plasma glucose level; (iv) postprandial glucose (PPG) level; (v) change in blood glucose level after a meal. PPG levels following a meal are an important measure of overall metabolic control in diabetes, and reduction of glycemic variability (GV) can be achieved via reductions in PPG. Both rapid-acting insulin analogues (RAIAs; aspart, glulisine and lispro) and regular human insulin (RHI) are widely used in the management of diabetes. Using data from 27 randomised controlled trials involving more than 7000 patients, we investigated the impact of RAIAs and RHI on measures of glycemic control and variability in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Our results show that, in patients with T1D, RAIAs are more effective than RHI at reducing PPG excursions and HbA1c. This indicates that glycemic control is better with RAIAs than with RHI. More data are required to assess the effects of RAIAs and RHI on glycemic control and variability in patients with T2D.In patients with diabetes, the risk of complications is increased by poor control of blood glucose levels and high blood glucose variability. Complications may include cardiovascular disease, eye problems and amputation. Control and variability of blood glucose levels can be evaluated using a range of measures, including (i) glycated haemoglobin (HbA1c) level at the end of the treatment period; (ii) change in HbA1c level during the treatment period; (iii) fasting plasma glucose level; (iv) postprandial glucose (PPG) level; (v) change in blood glucose level after a meal. PPG levels following a meal are an important measure of overall metabolic control in diabetes, and reduction of glycemic variability (GV) can be achieved via reductions in PPG. Both rapid-acting insulin analogues (RAIAs; aspart, glulisine and lispro) and regular human insulin (RHI) are widely used in the management of diabetes. Using data from 27 randomised controlled trials involving more than 7000 patients, we investigated the impact of RAIAs and RHI on measures of glycemic control and variability in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Our results show that, in patients with T1D, RAIAs are more effective than RHI at reducing PPG excursions and HbA1c. This indicates that glycemic control is better with RAIAs than with RHI. More data are required to assess the effects of RAIAs and RHI on glycemic control and variability in patients with T2D.

We evaluated the outcomes of revascularization in patients with chronic limb-threatening ischemia (CLTI) treated in real-world settings. This is a prospective multicenter cohort study with 12-month follow-up enrolling patients (n = 287) with CLTI undergoing open, endovascular, or hybrid lower extremity revascularization. The primary end point was amputation-free survival (AFS) at 12 months. Cox proportional analysis was used to determine independent predictors of amputation and restenosis. At 30 days, major adverse cardiovascular and major adverse limb events (MALE) rates were 3.1% and 2.1%, respectively. At 1 year, the overall survival rate was 88.8%, the AFS was 86.6%, and the primary patency was 70.5%. Freedom from MALE was 62.5%. After multivariate analysis, smoking (hazard ratio [HR] = 2.2, P = 0.04), renal failure (HR = 2.3, P = 0.03), Rutherford class (≥5) (HR = 3.2, P = 0.01), and below-the-knee disease (HR = 2.0, P = 0.05) were significant predictors of amputation; iloprost infusion (>10 vials) (HR = 0.64, P = 0.05) was a significant protective factor. Cilostazol administration (HR = 0.77, P = 0.05) was a significant protective factor for restenosis. Results from this prospective multicenter registry offer a consistent overview of clinical outcomes of CLTI patients at 1 year when adequately revascularized. Medical treatment, including statins, cilostazol and iloprost, were associated with improved 1-year freedom from restenosis and amputation.

Innovative biomarkers are needed to improve the management of patients with type 2 diabetes mellitus (T2DM). Blood circulating miRNAs have been proposed as a potential tool to detect T2DM complications, but the lack of tissue specificity, among other reasons, has hampered their translation to clinical settings. Extracellular vesicle (EV)-shuttled miRNAs have been proposed as an alternative approach. Here, we adapted an immunomagnetic bead–based method to isolate plasma CD31+ EVs to harvest vesicles deriving from tissues relevant for T2DM complications. Surface marker characterization showed that CD31+ EVs were also positive for a range of markers typical of both platelets and activated endothelial cells. After characterization, we quantified 11 candidate miRNAs associated with vascular performance and shuttled by CD31+ EVs in a large (n = 218) cross-sectional cohort of patients categorized as having T2DM without complications, having T2DM with complications, and control subjects. We found that 10 of the tested miRNAs are affected by T2DM, while the signature composed by miR-146a, -320a, -422a, and -451a efficiently identified T2DM patients with complications. Furthermore, another CD31+ EV-shuttled miRNA signature, i.e., miR-155, -320a, -342-3p, -376, and -422a, detected T2DM patients with a previous major adverse cardiovascular event. Many of these miRNAs significantly correlate with clinical variables held to play a key role in the development of complications. In addition, we show that CD31+ EVs from patients with T2DM are able to promote the expression of selected inflammatory mRNAs, i.e., CCL2, IL-1α, and TNFα, when administered to endothelial cells in vitro. Overall, these data suggest that the miRNA cargo of plasma CD31+ EVs is largely affected by T2DM and related complications, encouraging further research to explore the diagnostic potential and the functional role of these alterations.

Stress-induced hyperglycaemia (SIH) at hospital admission for acute coronary syndrome is associated with poor outcome, especially in patients without known diabetes. Nevertheless, insulin treatment in these subjects was not correlated with the reduction of mortality. This is likely due to the fact that SIH in the context of an acute coronary syndrome, compared to that in known diabetes, represents an epiphenomenon of other pathological conditions, such as adrenergic and renin-angiotensin system over-activity, hyperglucagonaemia, increase of circulating free fatty acids and pancreatic beta-cell dysfunction, which are not completely reversed by insulin therapy and so worsen the prognosis. Thus, SIH may be considered not only as a biomarker of organ damage, but also as an indicator of a more complex therapeutic strategy in these subjects. The aim of this review is to analyse the molecular mechanisms by which SIH may favour a worse prognosis in non-diabetic patients with acute coronary syndrome and identify new therapeutic strategies, in addition to insulin therapy, for a more appropriate treatment and improved outcomes.

Dataset related to: "Blood Co-Circulating Extracellular microRNAs and Immune Cell Subsets Associate with Type 1 Diabetes Severity" Abstract Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4+CD45RO+(miR-146a-5p and miR-223-3p) and CD4+CD25+cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity. Keywords: autoimmune; lymphocytes; microRNAs; biomarkers&nbsp

Dataset related to the article: "Plasma circulating miR-23~27~24 clusters correlate with the immunometabolic derangement and predict C-peptide loss in children with type 1 diabetes" Abstract Aims/hypothesis:We aimed to analyse the association between plasma circulating microRNAs (miRNAs) and the immunometabolic profile in children with type 1 diabetes and to identify a composite signature of miRNAs/immunometabolic factors able to predict type 1 diabetes progression. Methods:Plasma samples were obtained from children at diagnosis of type 1 diabetes (n = 88) and at 12 (n = 32) and 24 (n = 30) months after disease onset and from healthy control children with similar sex and age distribution (n = 47). We quantified 60 robustly expressed plasma circulating miRNAs by quantitative RT-PCR and nine plasma immunometabolic factors with a recognised role at the interface of metabolic and immune alterations in type 1 diabetes. Based on fasting C-peptide loss over time, children with type 1 diabetes were stratified into the following groups: those who had lost >90% of C-peptide compared with diagnosis level; those who had lost Results:Plasma circulating miR-23~27~24 clusters (miR-23a-3p, miR-23b-3p, miR-24-3p, miR-27a-3p and miR-27b-3p) were upmodulated upon type 1 diabetes progression, showed positive correlation with osteoprotegerin (OPG) and were negatively correlated with soluble CD40 ligand, resistin, myeloperoxidase and soluble TNF receptor in children with type 1 diabetes but not in healthy children. The combination of plasma circulating miR-23a-3p, miR-23b-3p, miR-24-3p, miR-27b-3p and OPG, quantified at disease onset, showed a significant capability to predict the decline in insulin secretion 12 months after disease diagnosis in two independent cohorts of children with type 1 diabetes. Conclusions/interpretations:We have pinpointed a novel miR-23a-3p/miR-23b-3p/miR-24-3p/miR-27b-3p/OPG plasma signature that may be developed into a novel blood-based method to better stratify patients with type 1 diabetes and predict C-peptide loss. Keywords:Biomarkers; Cardiovascular risk; Diabetic complications; Immunometabolism; Insulin secretion; Osteoprotegerin; microRNA.

A 27-years-old female with multiple autoimmune disorders presented to our cardiology unit for acute chest pain and worsening dyspnoea. Admission blood tests revealed increased serum levels of high-sensitive cardiac troponin, eosinophilic count and C-reactive protein. Laboratory findings, low QRS voltages by ECG, mildly reduced left ventricular systolic function in the context of pseudohypertrophy, mild and diffuse late gadolinium enhancement associated with markedly increased native T1 and T2 mapping levels assessed by echocardiography and cardiovascular magnetic resonance imaging, raised the suspicion of massive eosinophilic myocarditis, subsequently confirmed by histological examination of endomyocardial biopsy. Prompt initiation of immunosuppressive treatment allowed swift regression of myocardial inflammation and full recovery of left ventricular systolic function within one month. After ruling-out clonal myeloid disorder, lymphocyte-variant and reactive hypereosinophilia, the young lady was eventually diagnosed with idiopathic hypereosinophilic syndrome. This case report turns the spotlight on the role and importance of advanced multi-modality cardiovascular imaging for raising clinical suspicion of acute eosinophilic myocarditis, guiding diagnostic work-up and monitoring response to treatment.

Aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA) are common conditions affecting the elderly, and both carry high morbidity and mortality, particularly if left untreated. Dual AS-CA pathology is becoming increasingly recognized but with uncertain prognostic significance ([1][1],[2][2

Hydroxychloroquine has been proposed for the cure of the COVID-19 due to its anti-inflammatory and anti-viral action. People with diabetes are more prone to severe outcome if affected by COVID-19 and the use of Hydroxychloroquine might have some benefit in this setting. However, the use of Hydroxychloroquine in diabetes deserves particular attention for its documented hypoglycemic action.

Cardiovascular outcome trials (CVOTs) have demonstrated a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) treated by SGLT-2 inhibitors. This holds true in the presence of background therapy with statins in most patients. Noteworthy, this SGLT-2 inhibitors effect is unique because, at variance with other components of cardiorenal protection, MACE prevention does not appear to be a class effect. Here, we present meta-analysis of the four key CVOTs indicating a major role of renal function in determining the extent of MACE prevention, with the benefit increasing in more severe kidney disease, that is, a high-risk condition where effectiveness of the traditional approach with statins is reduced.

Plant cultivation systems for Bioregenerative Life-Support Systems in Space developed on Earth need to be tested in space, where reduced gravity alters the liquid and gas behavior both within the plant and between the plant and its surrounding environment, making the distribution of water and nutrients a critical issue. The ESA project "Precursor of Food Production Unit" (PFPU) aims to design a modular cultivation system for edible tuberous plants (such as potato and sweet potato) in microgravity, to be preliminary tested in ground conditions in the view of successive space application. Among the different modules of the PFPU demonstrator, the Root Module (RM) is the component physically hosting the plant and accommodating tubers and roots. This paper describes the step-by-step procedure adopted to realize the RM, including the design, the building, and the ground testing of its prototype. Specifically, the hydrological characterization of possible cultivation substrates, the set-up of the water distribution system, and the validation test of the assembled prototype in a tuber-to-tuber growing cycle of potato plants are described. Among six substrates tested, including three organic materials and three synthetic materials, cellulosic sponge was selected as the best one, based on the hydrological behavior in terms of air and water transport and water retention capacity. The water sensor WaterScout was successfully calibrated to monitor the water status in cellulosic sponge and to drive irrigation and fertigation management. The designed porous tubes-based distribution system, integrated with water sensors, was able to provide water or nutrient solution in a timely and uniform way in cellulosic sponge.

Insuline-Naaïve type 2 diabetic patients: a multidimensional evaluation on the role of glycated albumin Introduction: glycated Albumin (GA) is an innovative glycemic marker, that could be used in the clinical practice, as an add-on strategy, to the traditional glycemic monitoring systems, such as glycated haemoglobin (Hb1Ac) and fasting plasma glucose (FPG). The study aims at presenting the results of a multidimensional analysis conducted in Italy, exploring the main clinical, economic, ethical, social and organizational implications, related to the introduction of GA. Methods: an Health Technology Assessment (HTA) approach was implemented. The analysis considered the Italian National Healthcare Service (NHS) perspective, and assumed a 12-month time horizon, focusing on type 2 diabetes patients insulin-naïve, assuming oral therapy. The 9 HTA dimensions (derived from the Core Model developed by the European Network of HTA – EUnetHTA) were deployed, considering scientific evidence, health economics tools and qualitative approaches, through the administration of specific questionnaires to 15 diabetes experts. Results: literature reported better GA safety and efficacy profiles, thus being a predictor of the relative risk for diabetes complications development, and increasing the therapeutic success after 3 months of therapy (97.0% versus 71.6%). From an economic point of view, GA introduction resulted in an economic advantage of 1.06% and in a better tradeoff between costs sustained and efficacy gained. Considering a 7-item Likert Scale (ranging from -3 to +3), negative perceptions emerged with regard to equity aspects (0.13 versus 0.72) due to GA limited accessibility, whereas it would improve both patients (2.17 versus 1.33) and care givers (1.50 versus 0.83) quality of life. In the short term, GA required training courses and equipment update, whereas, in the long term, it could be considered the preferable solution from an organizational perspective (0.30 Conclusions: the results of this study demonstrated GA strategic relevance, its economic sustainability and feasibility, versus 0.01). as well as the potential clinical pathway improvement.

Residual inflammatory risk (RIR) is defined as persistent circulating levels of high sensitivity C-reactive protein (hs-CRP) >2 mg/L despite an optimal (

Background: Early and intensive glycaemic control provides long-term protection against the development of microvascular complications, a phenomenon defined legacy effect. Whether a legacy effect of high glucose exists also on macrovascular endpoints is uncertain. Methods and findings: We performed a systematic review of both randomized clinical trials (RCT)s and observational studies pertinent to the research question. We searched PubMed, Embase, Scopus and the Cochrane database up to January 31th 2020. Eligibility criteria for RCTs were: 1 - efficacy assessment of intensive glucose lowering treatment vs a less-stringent/conventional treatment; 2 - the inclusion of a post-active phase, observational follow-up; 3 - enrolment of patients with T1DM, pre-diabetes, and T2DM; and 4 - data report on major adverse cardiovascular events (MACE) incidence, which was the primary endpoint of this meta-analysis. We performed multiple meta-analyses of the available RCTs according to different scenarios considering the type of diabetes, diabetes duration, the presence of previous cardiovascular events, follow-up extension, and the incidence of MACE recorded only during the observational, post-active phase of the trials. Results from observational studies reporting the association between HbA1c levels during the first year after diabetes diagnosis and subsequent MACE incidence were also collected and are reported narratively. We included data from 7 RCTs and 40,346 patients. The intensive glucose-lowering approach significantly decrease the incidence of MACE compared with conventional treatment (OR 0.86, CI 0.77–0.96; p = 0.007) when considering all the available studies, with a more consistent effect (OR 0.73, CI 0.56–0.94; p = 0.01) in the case of RCTs enrolling patients with diabetes duration 10 years also yielded a relevant beneficial effect of the intensive approach (OR 0.71, CI 0.57, 0.88; p = 0.002). On the other hand, no effect was observed (OR 0.99, CI 0.92, 1.06; p = 0.81) when considering only the events recorded during the post-active, observational phases of the trials. Observational studies showed that HbA1c values >6.5% or 7% during the first year of diabetes diagnosis are associated with a higher incidence of late MACE with increased risk ranging from 19 up to 64%, according to the different study design and HbA1c stratification. Conclusions: These results support the recommendation regarding glucose-lowering treatment intensification in order to decrease the probability of having a macrovascular event in patients with short diabetes duration, no prevalent cardiovascular diseases, and long life-expectancy. On the other side, data from RCTs do not support the existence of a protective legacy effect on the macrovasculature beyond the period of intensive glycaemic treatment.

MILD combustion regime emerged as one of the most promising technology to ensure low pollutant emissions and large fuel flexibility. Large-scale use of such technology requires important developments of its numerical modelling. The difficulty of this task lies in the recirculation of mass and heat that results in coupling chemistry and turbulence phenomena. In this work, the effect of the internal exhaust gas recirculation on the performances of a tabulated chemistry model was investigated by carrying out an experimental and numerical study on a cyclonic burner. FGM (Flamelet Generated Manifold) model was adopted. It makes two main assumptions: a turbulent flame can be considered as an ensemble of 1D laminar flames (Flamelets), and the space of compositions can be represented by a lower-dimensional manifold by defining few controlling variables. In this work, two different 1D flame configurations and two controlling variables (a mixture fraction and a progress variable) were used. The comparisons between model and experiments were reported for different dilution conditions at inlet and two diluent species. Results showed that the role of the internal EGR is crucial in the establishment of MILD regimes. In fact, for air conditions the model is not able to predict the low and more distributed reactivity of the system. On the other hand, inlet diluted conditions show a good agreement with the experiments due to burned product effects. CO2-dilution instead of N2, improves the model results due to the lower reaction rates. Finally, the Flamelet configuration does not strongly affect the simulation results.

Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4+CD45RO+ (miR-146a-5p and miR-223-3p) and CD4+CD25+ cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity.

IntroductionThe major challenge for diabetes prevention is early identification of individuals at risk to allow for implementation of measures to delay the onset of future disease. Measures such as fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), and glycosylated hemoglobin (HbA1c) are equally appropriate for identifying pre-diabetes and diabetes, but do not all identify the disease in the same individual. We tested the utility of a diagnostic method combining FPG, 2hPG and HbA1c for early evaluation and easy identification of pre-diabetes.Research design and methods531 subjects underwent skin autofluorescence (SAF) and glycemia analyses. We created two classification groups based on the American Diabetes Association diagnosis guidelines: (1) based on 2hPG and (2) based on a new combination of three glycemia parameters (the three-criteria strategy (3-c)). Logistic regression modeling was used to estimate the associations.ResultsSAF showed high associations for both 3-c definition and 2hPG definition alone. These associations appeared stronger in 3-c than those in 2hPG. The non-invasive SAF measurement outperformed 2hPG in the detection of dysglycemia or pre-diabetes. Stepwise selections identified 1-hour postload glucose (1hPG) as variable identifying pre-diabetes using the 2hPG criterion, and the model based on 1hPG plus SAF appeared to be the best association using the 3-c strategy.Conclusions1hPG coupled with SAF showed a strong association in the evaluation of pre-diabetes using the 3-c method.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Aims/hypothesis: We aimed to analyse the association between plasma circulating microRNAs (miRNAs) and the immunometabolic profile in children with type 1 diabetes and to identify a composite signature of miRNAs/immunometabolic factors able to predict type 1 diabetes progression. Methods: Plasma samples were obtained from children at diagnosis of type 1 diabetes (n = 88) and at 12 (n = 32) and 24 (n = 30) months after disease onset and from healthy control children with similar sex and age distribution (n = 47). We quantified 60 robustly expressed plasma circulating miRNAs by quantitative RT-PCR and nine plasma immunometabolic factors with a recognised role at the interface of metabolic and immune alterations in type 1 diabetes. Based on fasting C-peptide loss over time, children with type 1 diabetes were stratified into the following groups: those who had lost >90% of C-peptide compared with diagnosis level; those who had lost

In the context of the COVID-19 continuous spreading, this paper focuses on the increased risk of diabetic patients regarding the metabolic control and the uncertainties related to SARS-CoV-2 infection. Chronic hyperglycaemia negatively affects the immune system, which triggers an increase of morbidity and mortality for viral infections. A key aspect of COVID-19 resides in the involvement of renin-angiotensin-aldosterone (RAAS) system that causes a cascade of reactions mediated by vasoactive peptides with implications in vasoconstriction, vascular permeability, oxidative stress remodelling and tissue injuries. Activation of RAAS at pulmonary level, is responsible for the local damage. Many questions regarding the treatment with ACE inhibitors and angiotensin receptor blockers were raised considering the correlation between RAAS and viral infection in diabetic patients.

Innovative solutions in terms of energy efficiency and pollutant emission abatement require the development of new combustion technologies. In particular, several solutions imply a process based on mixture dilution and preheating that can lead to very peculiar combustion regimes. New combustion concepts, such as moderate or intense low-oxygen dilution (MILD) combustion, rely on a local self-ignition mechanism as a result of the obtainment of burned gas/fresh reactant mixtures that lead to a process mainly stabilized by means of a distributed autoignition. Despite the very interesting features related to such a concept, several modeling issues have to be properly investigated, to permit the development of MILD combustion concepts through a computationally driven design. The evaluation of characteristic times, on both micro- and macroscales, is strongly influenced by the emerging characteristics related to a strong coupling between mixing and kinetic times as a result of the high dilution levels of such technologies. To include detailed chemistry in computational fluid dynamics simulations, the flamelet-generated manifold seems to be a promising choice. Specifically, the aim of this work is to prove the reliability of the tabulated chemistry method with respect to a cyclonic burner that was used as a test case for validation purposes. Reynolds-averaged Navier-Stokes simulations were realized, and a chemistry tabulation approach was used to take into account detailed chemistry effects. Finally, an assessment of the heat transfer mode was carried out by including both convection and radiation heat exchange in the modeling and comparing experimental and numerical results to temperature and gas concentration measurements obtained in several locations of the experimental apparatus. The computational tool was able to catch in a satisfactory manner the main features of the combustion regime in the cyclonic burner, and the validation was strongly improved when radiative heat transfer is included in the numerical model.

Aims To investigate the relationship between single therapeutic interventions and indicators of glycemic control in the PRISMA trial, a large study comparing the effects of intensive structured SMBG (ISM) vs. active control (AC) in non-insulin-treated type 2 diabetes (T2D). Methods Information was collected at four time points, corresponding to months 3, 6, 9, and 12 and visits 2, 3, 4, and 5, respectively. Data on therapeutic interventions, HbA1c levels and the number of hypoglycemic episodes at each visit were analyzed. Results Intensification of drug therapy occurred in 20.3% vs. 15.6%, and no change in 71.8% vs. 78.7% of visits for the ISM and AC groups, respectively. On the other hand, de-intensification and redistribution of drugs and/or drug dose occurred in a similar proportion of visits. Intensification of drug therapy in both groups was associated with significant reductions in HbA1c vs. the previous visit, while de-intensification of therapy led to a significant increase in HbA1c in the AC group only. Conclusions. Our data strongly support that structured SMBG has clinical value in reducing HbA1c in non-insulin-treated T2D and suggest that this clinical benefit may be mediated by more appropriate and timely changes in drug therapy.

Emerging evidence is showing a range of beneficial effects for GLP-1 receptor agonists and especially SGLT-2 inhibitors on the cardio-renal axis in patients with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Preliminary findings suggest that: 1- such benefit extends also to patients with T2D without pre-existing CVD; and 2- background therapies do not modify the effect of these drugs. Given these considerations, some authors advanced the hypothesis that these novel agents might undermine the first-line position of metformin in the treatment algorithm of T2D. Here, we briefly discuss some pros and cons of such scenario, proposing a "starting" combination therapy with metformin plus one novel agent with trial-proven benefit as the best option to make use of the available knowledge and minimize the risk of complications in patients with newly diagnosed T2D.

BackgroundThere is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes.MethodsUsing data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability.ResultsAfter adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39–1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality).ConclusionsHigh body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.