Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes.
words)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: In this retrospective cohort study we analyzed the relationship between clinical characteristics, including body mass index (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 kg/m2) and severe obesity (BMI >35 kg/m2) 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, Chi square test for trend), and it was greatest in patients with BMI >35 kg/m 2 (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 kg/m 2 vs patients with BMI <25 kg/m 2 was 7. 36 (1.63-33.14; p=0.02) Conclusion: 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.
Accepted Article
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