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Aims/hypothesisThis is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).MethodsThe CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days.ResultsWe included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors.Conclusions/interpretationIn patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period.Trial registrationClinicaltrials.gov identifier: NCT04324736

Background Rare syndromes of lipodystrophy and insulin-resistance display heterogeneous clinical expressions. Their early recognition, diagnosis and management are required to avoid long-term complications. Objective We aimed to evaluate the patients’ age at referral to our dedicated national reference center in France and their elapsed time from first symptoms to diagnosis and access to specialized care. Patients and methods We analyzed data from patients with rare lipodystrophy and insulin-resistance syndromes referred to the coordinating PRISIS reference center (Adult Endocrine Department, Saint-Antoine Hospital, AP-HP, Paris), prospectively recorded between 2018 and 2023 in the French National Rare Disease Database (BNDMR, Banque Nationale de Données Maladies Rares ). Results A cohort of 292 patients was analyzed, including 208 women, with the following diagnosis: Familial Partial LipoDystrophy (FPLD, n  = 124, including n  = 67 FPLD2/Dunnigan Syndrome); Acquired lipodystrophy syndromes ( n  = 98, with n  = 13 Acquired Generalized Lipodystrophy, AGL); Symmetric cervical adenolipomatosis ( n  = 27, Launois-Bensaude syndrome, LB), Congenital generalized lipodystrophy ( n  = 18, CGL) and other rare severe insulin-resistance syndromes ( n  = 25). The median age at referral was 47.6 years [IQR: 31–60], ranging from 25.2 (CGL) to 62.2 years old (LB). The median age at first symptoms of 27.6 years old [IQR: 16.8–42.0]) and the median diagnostic delay of 6.4 years [IQR: 1.3–19.5] varied among diagnostic groups. The gender-specific expression of lipodystrophy is well-illustrated in the FPLD2 group (91% of women), presenting with first signs at 19.3 years [IQR: 14.4–27.8] with a diagnostic delay of 10.5 years [IQR: 1.8–27.0]. Conclusion The national rare disease database provides an important tool for assessment of care pathways in patients with lipodystrophy and rare insulin-resistance syndromes in France. Improving knowledge to reduce diagnostic delay is an important objective of the PRISIS reference center.

Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2), unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. ClinicalTrials.gov NCT01530685.

Background Although metreleptin replacement therapy was shown to improve metabolic alterations in lipodystrophic syndromes, patients’ adherence and satisfaction with treatment have never been evaluated. The 20 patients with lipodystrophic syndromes participating in the French compassionate program of metreleptin therapy filled in a self-questionnaire including an Adherence Evaluation Test, the Treatment Satisfaction Questionnaire for Medication (TSQM®-vII), and items about physical appearance. Results 15 patients were women, median age was 32.5 years (IQT 25–75 (16.2;49.5), 18 had diabetes. Adherence with metreleptin (one daily subcutaneous injection) was poor in 25%, excellent in 25% and acceptable in 50% of patients. On a 0-to-100 scale, patients’ satisfaction scores reached 66.7 (52.1;81.2) for effectiveness, 55.6 (44.4;66.7) for ease/comfort of use, and 83.3 (52.1;83.3) for global satisfaction with metreleptin therapy. Self-reported side effects were frequent injection site reactions 100 (79.2;100). Satisfaction scores did not differ in patients with partial ( n  = 10) or generalized ( n  = 10) lipodystrophic syndromes, did not correlate with metabolic improvement, but were significantly higher in compliant patients with fewer side effects. Morphological appearance was reported improved under metreleptin therapy in 13 among 17 patients. Conclusions Metreleptin increases health self-perception and decreases morphotype-associated stigmatization in most patients with lipodystrophic syndromes, but poor comfort of use and local side effects weaken adherence.

Background Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered.

Objective To describe the bone imaging features of lipodystrophies in the largest cohort ever published. Materials and Methods We retrospectively examined bone imaging data in 24 patients with lipodystrophic syndromes. Twenty-two had genetic lipodystrophy: 12/22 familial partial lipodystrophy (FPLD) and 10/22 congenital generalized lipodystrophy (CGL), 8 with AGPAT2-linked CGL1 and 2 with seipin-linked CGL2. Two patients had acquired generalized lipodystrophy (AGL) in a context of non-specific autoimmune disorders. Skeletal radiographs were available for all patients, with radiographic follow-up for two. Four patients with CGL1 underwent MRI, and two of them also underwent CT. Results Patients with FPLD showed non-specific degenerative radiographic abnormalities. Conversely, CGL patients showed three types of specific radiographic alterations: diffuse osteosclerosis (in 7 patients, 6 with CGL1 and 1 with CGL2), well-defined osteolytic lesions sparing the axial skeleton (7 CGL1 and 1 CGL2), and pseudo-osteopoikilosis (4 CGL1). Pseudo-osteopoikilosis was the sole bone abnormality observed in one of the two patients with AGL. Osteolytic lesions showed homogeneous low signal intensity (SI) on T1-weighted and high SI on T2-weighted MR images. Most of them were asymptomatic, although one osteolytic lesion resulted in a spontaneous knee fracture and secondary osteoarthritis in a patient with CGL1. MRI also showed diffuse fatty bone marrow alterations in patients with CGL1, with intermediate T1 and high T2 SI, notably in radiographically normal areas. Conclusions The three types of peculiar imaging bone abnormalities observed in generalized lipodystrophic syndromes (diffuse osteosclerosis, lytic lesions and/or pseudo-osteopoikilosis) may help clinicians with an early diagnosis in pauci-symptomatic patients.

The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated with severe aortic valve stenosis. We further describe the cardiovascular involvement associated with the syndrome in her family. We identified seven members with a general presentation suggestive of progeroid syndrome. All of them presented heart conduction abnormalities: degenerative cardiac diseases such as coronary artery disease (two subjects) and aortic stenosis (three subjects) occurred in the 3rd–5th decade, and a young patient developed a severe dilated cardiomyopathy, leading to death at 15 years of age. The likely pathogenic variant was found in all the patients who consented to carry out the genetic test. This diverse family cardiologic phenotype emphasizes the complex molecular background at play in lamin-involved cardiac diseases, and the need for early and thorough cardiac evaluations in patients with laminopathic progeroid syndromes.

Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

Aims/hypothesisCoronavirus 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.MethodsWe 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.ResultsThe 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, HbA1c, 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/interpretationsIn 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 registrationclinicaltrials.gov NCT04324736.