Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m²; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA_1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. Trial registration: clinicaltrials.gov NCT04324736.

To investigate whether atherogenic dyslipidemia, a dyslipidemic profile combining elevated triglycerides and low high-density lipoprotein (HDL) cholesterol, is predictive of risk of silent myocardial ischemia (SMI) or angiographic coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes. Cohort study in 1080 asymptomatic patients with type 2 diabetes with a normal resting electrocardiogram, at least one additional cardiovascular risk factor and low density lipoprotein (LDL) cholesterol <3.35 mmol/L. Patients initially underwent screening for SMI by stress myocardial scintigraphy. Patients with SMI underwent coronary angiography. Overall, 60 (5.5 %) patients had atherogenic dyslipidemia (triglycerides ≥2.26 mmol/L and HDL cholesterol ≤0.88 mmol/L). In multivariate analyses taking into account the parameters associated in univariate analyses with SMI and then CAD, atherogenic dyslipidemia was associated with SMI (odds ratio 1.8[1.0–3.3]), as were male gender (OR 2.1[1.5–2.9]), BMI (OR 0.97[0.94–0.997]), retinopathy (OR 1.4[1.1–1.9]), peripheral occlusive arterial disease (POAD: OR 2.5[1.6–3.8]) and mean blood pressure (OR 1.01[1.00–1.03]); atherogenic dyslipidemia was associated with CAD (OR 4.0[1.7–9.2]), as were male gender (OR 3.0[1.6–5.6]), BMI (OR 0.94[0.90–0.995]), retinopathy (OR 1.7[1.0–2.9], POAD (OR 4.0[2.1–7.4]) and mean blood pressure (OR 1.03[1.01–1.05]). In the subgroup of 584 patients with LDL cholesterol <2.6 mmol/L, atherogenic dyslipidemia was also associated with CAD (OR 3.6[1.5–9.0]). Atherogenic dyslipidemia was associated with an increased risk of SMI and silent CAD in patients with type 2 diabetes and LDL cholesterol levels <3.35 mmol/L. Specific management of atherogenic dyslipidemia might help reducing the high residual burden of cardiovascular disease.

The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination coverage in at-risk patients and to examine factors associated with pneumococcal vaccination in France. In this annual cross-sectional study, at-risk patients were extracted between 2014 and 2018 from the National Health Insurance's (NHI) General scheme's claims database with their vaccine reimbursements. Descriptive analyses and a logistic model were performed to assess the influence of healthcare use and medical and demographic factors on pneumococcal vaccination. In 2018, 4.5% of 4,045,021 at-risk adults were up to date with their pneumococcal vaccination. During the study period, the number of patients with chronic medical conditions (86% of 4,045,021) increased by 10.1%, but vaccination coverage decreased from 12.9% to 2.9%. The population with immunocompromised status (14% of 4,045,021) increased by 16.2% and vaccination coverage from 10.3% to 18.8%. Influenza vaccination coverage was much higher and stable (around 45.0%). Factors associated with pneumococcal vaccination were: immunocompromised status vs. having a chronic medical condition (odds ratio [OR] 4.72), influenza vaccination (OR 2.36-3.42), hepatitis B vaccination (OR 2.82), DTPolio vaccination (OR 1.52), ≥5 specialist physicians' visits (OR 1.17), and age above 74 (OR 1.12). Pneumococcal vaccine dispensing was extremely low (median of 9per GP,1per specialist over 9 years) despite frequent healthcare visits. Pneumococcal and influenza vaccination coverage of adults at risk of pneumococcal disease fell well below public health expectations. Invitations for pneumococcal vaccination should be sent by the NHI to high-risk patients. Patient management protocols should include pneumococcal vaccination. Patients with multiple comorbidities are a high-priority population given the large potential health gains offered by pneumococcal vaccination. Commitment of both scientific societies and health authorities is urgently needed to increase vaccination coverage in at-risk populations.

Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity. We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development. 30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression. Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR. Our results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.

Objective: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m²) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI.Methods: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m², including 39 with (BS+) and 90 without (BS−) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference.Results: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS− groups.Conclusions: This study is the first, to the authors’ knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m² and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.