The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.

BackgroundApelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery.MethodsWe recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay).ResultsPatients with T2D had significantly higher serum apelin levels compared to controls (1.23±1.1 ng/mL vs 0.91±0.7 ng/mL, P<0.001) and to T1D subjects (0.73±0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01).ConclusionsOur study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.

Aims/IntroductionMeasurement of glycated hemoglobin (HbA1c) has been recommended for the diagnosis of diabetes and prediabetes. However, epidemiological studies have shown significant discordance between HbA1c and glucose-based tests. Of the factors that could influence agreement between HbA1c and the oral glucose tolerance test (OGTT), bodyweight has not been fully evaluated. The aims of the present study were to evaluate the impact of HbA1c criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine HbA1c in relation to body mass index.Materials and MethodsTwo cohorts were studied, one from an obesity clinic (n = 592) and one from subjects undergoing screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement.ResultsIn the obese cohort, HbA1c ≥6.5% (≥48 mmol/mol) showed a sensitivity of 69.3% for diabetes, whereas HbA1c 5.7–6.4% (39–46 mmol/mol) did not identify prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c had low sensitivities for both diabetes (39.2%) and prediabetes (53.3%). When participants were stratified according to body mass index class I–III, HbA1c agreement with the OGTT for diabetes was much higher (80%, P < 0.005) in class I obesity compared with class II–III obesity; whereas for prediabetes, HbA1c had a low sensitivity in all obesity classes.ConclusionsThe agreement between HbA1c, fasting plasma glucose and 2-h glucose post-OGTT for the diagnosis of prediabetes was poor in our Italian population; whereas HbA1c ≥6.5% showed a relatively good agreement with OGTT for the diagnosis of diabetes. For the first time, we have shown that obesity class influences the diagnostic performance of HbA1c.

The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

Background:During the epidemic’s peak of COVID-19, scientific societies published recommendations on biotherapy and targeted synthetic treatment (B/TST) use in patients with chronic articular inflammatory diseases, inflammatory bowel diseases, and psoriasis.Objectives:The objective was to evaluate the impact of COVID-19 in France on initiation and renewal of B/TST.Methods:LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. The impact of B/TST initiation and renewal were studied using 2019 as reference and dispense deliveries data of pharmacies with regular flew in order to perform the comparison. B/TST considered were abatacept, anti-TNF, anti-IL6, anti-IL17, anti-IL12/23 or anti-IL23, JAK inhibitors (JAKi) and other classes such as aprelimast, aminosalicylates (AS), hydroxychloroquine (HCQ), and methotrexate (MTX). A treatment initiated was defined as a treatment not delivered in the past 12 months, and conversely for a treatment renewal. Results were presented as raw one and expressed in percentage of patients having at least one B/TST delivery in each therapeutic classes of interest in 2020 compared to 2019 used as reference year (period from week 12 to week 19 considered and corresponding to the lockdown period in France).Results:During the lockdown period, a decrease in initiation was observed for patients treated with: abatacept (405 in 2019 vs 227 in 2020: -44%, p<0.001), anti-TNF (1156 vs 1058, -31%, p<0.001), anti-IL17 (415 vs 206, -50%, p<0.001), anti-IL12-23 (395 vs 339, -12%, p=0.16), JAKi (289 vs 174, -39%, p=0.006), contrasting with an increase for Tociliumab (117 vs 445, +152%, p=0,01). We found a decrease of 7% (2171 vs 2015, p=0,35), 44% (405 vs 227, p<0.001), 30% (3430 vs 2390, p p<0.001) of AS, aprelimast and MTX initiation, respectively, and an increase of 173% (1708 vs 4671, p=0.11) of HCQ initiation. No decrease for the renewal of B/TST was observedConclusion:During the epidemic’s peak, initiation of AS, MTX, biotherapies (except for tocilizumab), and JAKi dramatically decreased without impacting their renewal. Two treatments were mainly initiated, tocilizumab probably due to a switch from intravenous to subcutaneous injection and HCQ in relation to its presumably effect on COVID-19. Overall, recommendations from scientific societies have been followed.Disclosure of Interests:None declared