Mikaël Chetboun

Objective The COVID‐19 pandemic is rapidly spreading worldwide, notably in Europe and North America where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has not been fully documented. Methods This retrospective cohort study analyzed the relationship between clinical characteristics, including BMI, and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS‐CoV‐2 in a single French center. Results Obesity (BMI > 30) and severe obesity (BMI > 35) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories ( P < 0.01, χ 2 test for trend), and it was greatest in patients with BMI > 35 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex ( P < 0.05) and BMI ( P < 0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI > 35 versus patients with BMI < 25 was 7.36 (1.63‐33.14; P = 0.02). Conclusions The present study showed a high frequency of obesity among patients admitted in intensive care for SARS‐CoV‐2. Disease severity increased with BMI. Obesity is a risk factor for SARS‐CoV‐2 severity, requiring increased attention to preventive measures in susceptible individuals.

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies.

OBJECTIVE: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.

Abstract Objective Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID‐19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID‐19. Methods Patients admitted to intensive care units for COVID‐19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28‐day mortality, respectively. Results A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9‐72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m 2 (25.4‐32.3); a total of 1,080 patients (73.9%) required IMV; and the 28‐day mortality estimate was 36.1% (95% CI: 33.0‐39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12‐1.45) per 5 kg/m 2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06‐2.64]). Conclusions In critically ill COVID‐19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.