BACKGROUND:The hypothalamus (HT) plays a crucial role in regulating eating behaviors. Disruptions in its function have been linked to the development of weight-related disorders. Nevertheless, its characterization remains a challenge. OBJECTIVES:We assessed the structural alterations of individual HT nuclei related to eating behaviors in patients with weight-related disorders, and their association with body mass index (BMI) and severity of eating disorders. METHODS:Forty-four young females with normal weight (HC, n = 21), restrictive anorexia nervosa (AN, n = 13), and living with obesity (OB, n = 10) were explored in vivo using 7-T high-resolution (0.6 mm isotropic voxel) T1 quantitative magnetic resonance imaging (MRI). Volumes and quantitative T1 values of individual HT nuclei were compared after whole-brain normalization using nonparametric tests (corrected for multiple comparisons for groups and regions). We investigated the parameters associated with BMI and eating disorders, such as MRI parameters of HT nuclei, ghrelin and leptin levels, depression, and anxiety using multivariate nonlinear partial least square (NIPALS). RESULTS:Both AN and OB showed higher volumes of HT relative to HC (Zscores: 0.78 ± 1.06; 1.43 ± 1.51). AN showed significantly higher volumes and T1 values of the right paraventricular nucleus (PaVN) (volume Zscore: 1.82 ± 1.45; T1 Zscore: 3.76 ± 4.67), and higher T1 values of the left PaVN (Zscore: 2.25 ± 2.37) and right periventricular nuclei (Zscore: 3.73 ± 4.81). NIPALS models showed that lower BMI in AN was associated with structural alterations of the bilateral PaVN, right anterior commissure, and left fornix (FX). Higher BMI in OB was associated with structural alterations within the right PaVN, bilateral FX, left posterior hypothalamic nucleus, right lateral HT, and right anterior hypothalamic area. Finally, the severity of eating disorders was associated with larger structural alterations within the bilateral PaVN, bilateral arcuate hypothalamic nuclei, right bed nucleus of stria terminalis, left medial preoptic nucleus, and right tubero-mammillary hypothalamic nucleus. CONCLUSIONS:Weight-related disorders are associated with significant micro and macrostructural alterations in HT nuclei involved in eating behaviors.

IntroductionCurrently, gastroesophageal reflux disease (GERD) is the main side effect after sleeve gastrectomy (SG), causing discomfort and potential long-term risks. Surgical techniques combining fundoplication with SG are being evaluated to limit postoperative GERD.MethodsThis single-center retrospective study evaluated patients who underwent SG with posterior fundoplication in the context of GERD between 2018 and 2021, with postoperative follow-up up to 24 months. The results were compared to a control group (ratio 1 to 4) who had SG without fundoplication. Observed total weight loss (TWL) was compared to predicted TWL using the Sophia multinational study's machine learning-based calculator.ResultsThe series included 22 patients (mean body mass index 44.4 kg/m2) with GERD conditions: GERD symptoms (n = 15), hiatal hernia (n = 6), esophagitis (n = 7), and Barrett's esophagus (n = 5). Two patients required reoperation, including one for valve perforation. At 2 years, GERD was present in three patients (13.6%), including two who regularly took proton pump inhibitors. Compared to the control group (n=88), the frequency of GERD persisting at 2 years was significantly reduced in the SG with fundoplication group (p=0.05). The TWL at 12 and 24 months was 27.7% and 26.1%, respectively, with no significant difference compared to the weight predicted by the model, nor compared to the control group.ConclusionThe combination of posterior fundoplication with SG can be proposed in patients with GERD who have a contraindication to Roux-en-Y gastric bypass. Specific morbidity may exist at the beginning of the experience.

The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D). EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification. Median age of the study population was 61 [54;67], with a majority of men (57

En mars 2020, la maladie à coronavirus 2019 (COVID-19) causée par le SARS-CoV-2 a été déclarée par l'OMS comme pandémie mondiale. L'obésité a rapidement été identifiée comme un facteur de risque indépendant de mauvais pronostic avec plus de risques de survenue de syndrome de détresse respiratoire aigüe, d'évènements cardio-vasculaires et thrombo-emboliques, de passage en réanimation et de mortalité. Le rôle du tissu adipeux viscéral blanc, qui augmente chez les personnes souffrant d'obésité, semble important dans cette pathogenèse, car il constitue un réservoir viral pour le SARS-CoV-2, par l'intermédiaire des récepteurs de l'enzyme de conversion de l'angiotensine 2. Après l'infection des cellules hôtes, l'activation des cytokines pro-inflammatoires crée un environnement propice à « l'orage cytokinique », et au syndrome d'activation macrophagique, associés à la progression vers le syndrome de détresse respiratoire aiguë. Dans l'obésité, la propagation systémique du virus, son entrée et son excrétion prolongée dans le tissu adipeux déjà inflammé peuvent stimuler les réponses immunitaires et l'amplification subséquente d'une cascade de cytokines, ce qui aggrave l'évolution de la maladie. L'hyperactivation endothéliale induite par le SARS-CoV-2 combinée à l'état d'hypofibrinolyse et de dysfonction endothéliale présents dans l'obésité augmente le risque d'événements thrombo-emboliques. Le volume de tissu adipeux viscéral et épicardique mesuré par scanner semble être un bon marqueur pronostique de ces évolutions défavorables. De plus, les réponses vaccinales semblent être moindres chez ces patients par une réponse humorale précoce plus faible nécessitant de continuer de diffuser des messages de prévention, et d'encourager les rappels vaccinaux dans cette population. L'objectif de cette revue est de déterminer le rôle du tissu adipeux dans le pronostic défavorable des patients infectés par le SARS-CoV-2 atteints d'obésité. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Publié par Elsevier Masson SAS. Tous droits réservés. In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the WHO. Obesity was rapidly identified as an independent risk factor for poor prognosis, with an increased risk of acute respiratory distress syndrome, cardiovascular and thrombo-embolic events, admission to intensive care and mortality. The white visceral adipose tissue, which increases in people suffering from obesity, appears to have a key role in this pathogenesis, as it constitutes a viral reservoir for SARS-CoV-2 through angiotensin 2-converting enzyme receptors. Following infection of host cells, activation of pro-inflammatory cytokines creates an environment suitable to the 'cytokine storm' and macrophage activation syndrome, associated with a risk of progression to acute respiratory distress syndrome. In obesity, the systemic spread of the virus, its entry and prolonged excretion into already inflamed adipose tissue can stimulate immune responses and the subsequent amplification of a cytokine cascade, worsening the course of the disease. The endothelial hyperactivation induced by SARS-CoV-2 combined with the state of hypofibrinolysis and endothelial dysfunction present in obesity increases the risk of thrombo-embolic events. The volume of visceral and epicardial adipose tissue measured by CT scan appears to be a good prognostic marker for these unfavorable outcomes. In addition, vaccine responses appear to be lower in these patients due to a weaker early humoral response, which means that prevention messages need to continue to be disseminated and booster vaccinations encouraged in this population. The aim of this review is to determine the role of adipose tissue in the poor prognosis of obese patients infected with SARS-CoV-2. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

L’obésité représente aujourd’hui un problème de santé mondial en constante augmentation. Comprendre les mécanismes qui sous-tendent la formation, la croissance et le fonctionnement du tissu adipeux semble crucial pour lutter contre cette maladie et ses complications, telles que le diabète de type 2 et les maladies cardiovasculaires. En France, l’obésité est en hausse, en particulier chez les jeunes adultes et les enfants. Dans cette revue, nous discutons de la composition cellulaire du tissu adipeux blanc, en mettant en lumière les avancées récentes dans la caractérisation des différentes populations cellulaires qui le composent. Nous explicitons également les conséquences métaboliques de la répartition des graisses corporelles, en soulignant l’importance des tissus adipeux brun et beige dans la régulation du métabolisme. Ces tissus thermogéniques offrent des avantages métaboliques notables, ouvrant ainsi la voie à des opportunités pour la recherche et le développement de stratégies thérapeutiques visant à lutter contre les affections métaboliques. De plus, nous abordons la relation entre sénescence cellulaire et dysfonctionnement métabolique lié à l’obésité, ainsi que les nouvelles perspectives de recherche dans le domaine de la communication intercellulaire et de la fonction mitochondriale. En définitive, cette revue propose une vue d’ensemble des avancées récentes dans la compréhension de l’obésité à l’échelle du tissu adipeux.

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS- CoV- 2 was declared a global pandemic by the WHO. Obesity was rapidly identified as an independent risk factor for poor prognosis, with an increased risk of acute respiratory distress syndrome, cardiovascular and thrombo-embolic events, admission to intensive care and mortality. The white visceral adipose tissue, which increases in people suffering from obesity, appears to have a key role in this pathogenesis, as it constitutes a viral reservoir for SARS-CoV-2 through angiotensin 2-converting enzyme receptors. Following infection of host cells, activation of pro-inflammatory cytokines creates an environment suitable to the 'cytokine storm' and macrophage activation syndrome, associated with a risk of progression to acute respiratory distress syndrome. In obesity, the systemic spread of the virus, its entry and prolonged excretion into already inflamed adipose tissue can stimulate immune responses and the subsequent amplification of a cytokine cascade, worsening the course of the disease. The endothelial hyperactivation induced by SARS-CoV-2 combined with the state of hypofibrinolysis and endothelial dysfunction present in obesity increases the risk of thrombo-embolic events. The volume of visceral and epicardial adipose tissue measured by CT scan appears to be a good prognostic marker for these unfavorable outcomes. In addition, vaccine responses appear to be lower in these patients due to a weaker early humoral response, which means that prevention messages need to continue to be disseminated and booster vaccinations encouraged in this population. The aim of this review is to determine the role of adipose tissue in the poor prognosis of obese patients infected with SARS-CoV-2. (c) 2023 Societe francophone nutrition clinique et metabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

L'obésité représente aujourd'hui un problème de santé mondial en constante augmentation. Comprendre les mécanismes qui sous-tendent la formation, la croissance et le fonctionnement du tissu adipeux semble crucial pour lutter contre cette maladie et ses complications, telles que le diabète de type 2 et les maladies cardiovasculaires. En France, l'obésité est en hausse, en particulier chez les jeunes adultes et les enfants. Dans cette revue, nous discutons de la composition cellulaire du tissu adipeux blanc, en mettant en lumière les avancées récentes dans la caractérisation des différentes populations cellulaires qui le composent. Nous explicitons également les conséquences métaboliques de la répartition des graisses corporelles, en soulignant l'importance des tissus adipeux brun et beige dans la régulation du métabolisme. Ces tissus thermogéniques offrent des avantages métaboliques notables, ouvrant ainsi la voie à des opportunités pour la recherche et le développement de stratégies thérapeutiques visant à lutter contre les affections métaboliques. De plus, nous abordons la relation entre sénescence cellulaire et dysfonctionnement métabolique lié à l'obésité, ainsi que les nouvelles perspectives de recherche dans le domaine de la communication intercellulaire et de la fonction mitochondriale. En définitive, cette revue propose une vue d'ensemble des avancées récentes dans la compréhension de l'obésité à l'échelle du tissu adipeux. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Publié par Elsevier Masson SAS. Tous droits réservés. Obesity represents a growing global health issue today. Understanding the mechanisms underlying the formation, growth, and function of adipose tissue is crucial in combating this disease and its associated complications, such as type 2 diabetes and cardiovascular diseases. In France, obesity is on the rise, particularly among young adults and children. In this review, we discuss the cellular composition of white adipose tissue, highlighting recent advances in the characterisation of various cell populations. We also explore the metabolic implications of body fat distribution, emphasizing the importance of brown and beige adipose tissues in metabolism regulation. These thermogenic tissues offer significant metabolic benefits, opening up promising opportunities in research and development of therapeutic strategies to address obesity-related metabolic disorders. Furthermore, we discuss the relationship between cellular senescence and obesity-related metabolic dysfunction, along with new research in the field of intercellular communication and mitochondrial recycling. Finally, this review provides a comprehensive overview of recent developments in the understanding of obesity at adipose cells level. © 2023 Société francophone nutrition clinique et métabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

Obesity represents a growing global health issue today. Understanding the mechanisms underlying the formation, growth, and function of adipose tissue is crucial in combating this disease and its associated complications, such as type 2 diabetes and cardiovascular diseases. In France, obesity is on the rise, particularly among young adults and children. In this review, we discuss the cellular composition of white adipose tissue, highlighting recent advances in the characterisation of various cell populations. We also explore the metabolic implications of body fat distribution, emphasizing the importance of brown and beige adipose tissues in metabolism regulation. These thermogenic tissues offer significant metabolic benefits, opening up promising opportunities in research and development of therapeutic strategies to address obesity-related metabolic disorders. Furthermore, we discuss the relationship between cellular senescence and obesity-related metabolic dysfunction, along with new research in the field of intercellular communication and mitochondrial recycling. Finally, this review provides a comprehensive overview of recent developments in the understanding of obesity at adipose cells level. (c) 2023 Societe francophone nutrition clinique et metabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

Background:Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved.Objectives:This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function.Methods:A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain.Results:MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58).Conclusions:Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

BENEFITS OF BARIATRIC SURGERY ON WEIGHT LOSS, DEVELOPMENT OF COMORBIDITIES AND MORTALITY Bariatric surgery, mainly sleeve gastrectomy (SG) and gastric bypass (GBP) in France, induces a greater and more durable weight loss than current treatments in cases of morbid or severe obesity with co-morbidity. Bariatric surgery can also improve, or even put into remission, most of the pathologies associated with obesity, such as type 2 diabetes, sleep apnea, arterial hypertension, dyslipidemia... An improvement in the quality of life and life expectancy of patients after bariatric surgery has been observed, even considering the operative risk and the discomfort generated by these procedures. The differences in efficacy, risk and discomfort at short and long term between SG and GPB do not allow to define a procedure of choice at the present time. The great effectiveness of bariatric surgery on diabetes associated with obesity, corresponding to the metabolic surgery concept, will probably lead to an extension of the operative indications.

Hypothalamus (HT), this small structure often perceived through the prism of neuroimaging as morphologically and functionally homogeneous, plays a key role in the primitive act of feeding. The current paper aims at reviewing the contribution of magnetic resonance imaging (MRI) in the study of the role of the HT in food intake regulation. It focuses on the different MRI techniques that have been used to describe structurally and functionally the Human HT. The latest advances in HT parcellation as well as perspectives in this field are presented. The value of MRI in the study of eating disorders such as anorexia nervosa (AN) and obesity are also highlighted.

Background: To develop a deep-learning (DL) pipeline that allowed an automated segmentation of epicardial adipose tissue (EAT) from low-dose computed tomography (LDCT) and investigate the link between EAT and COVID-19 clinical outcomes. Methods: This monocentric retrospective study included 353 patients: 95 for training, 20 for testing, and 238 for prognosis evaluation. EAT segmentation was obtained after thresholding on a manually segmented pericardial volume. The model was evaluated with Dice coefficient (DSC), inter-and intraobserver reproducibility, and clinical measures. Uni-and multi-variate analyzes were conducted to assess the prognosis value of the EAT volume, EAT extent, and lung lesion extent on clinical outcomes, including hospitalization, oxygen therapy, intensive care unit admission and death. Results: The mean DSC for EAT volumes was 0.85 ± 0.05. For EAT volume, the mean absolute error was 11.7 ± 8.1 cm3 with a non-significant bias of −4.0 ± 13.9 cm3 and a correlation of 0.963 with the manual measures (p < 0.01). The multivariate model providing the higher AUC to predict adverse outcome include both EAT extent and lung lesion extent (AUC = 0.805). Conclusions: A DL algorithm was developed and evaluated to obtain reproducible and precise EAT segmentation on LDCT. EAT extent in association with lung lesion extent was associated with adverse clinical outcomes with an AUC = 0.805.

Abstract Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant genetic disorder classically characterized by lifelong mild-to-moderate asymptomatic hypercalcemia with inappropriately normal to elevated serum parathyroid hormone (PTH) concentrations and hypocalciuria, best expressed by a urine calcium-to-creatinine clearance ratio (CCCR)<0.01[1,2]. FHH prevalence is estimated between 1:10 000 to 1:100 000[3,4]. In 60% of cases, FHH is due to CASR inactivating mutation[5]. More rarely FHH is due to AP2S1 or GNA11 inactivating mutation, both genes encoding for proteins involved downstream of CASR activation[6]. These molecular alterations are found in all parathyroid cells, explaining disease persistence following partial parathyroidectomy and the ineffective surgical management of these patients. FHH phenotypes could however overlap with primary hyperparathyroidism (PHPT). Indeed, even if patients with FHH are currently asymptomatic, some of them present chondrocalcinosis, kidney stones or bone fracture and very high level of PTH or calcemia[7]. Nonetheless, the distinction has to be adressed since the therapeutic approach significantly differs between these two conditions. Surgery is usually recommended for PHPT[8] while follow-up is preferred in the latter case[9,10]. We report and discuss 7 cases, 6 out 7 being operated for a presumed PHPT.

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

Abstract Objective Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. Methods We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). Results The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49–0.88)), death (OR: 0.49 (0.30–0.79)) and ICU admission (OR: 0.57 (0.43–0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43–0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. Conclusions In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Diabetes mellitus (DM) has been identified as a risk factor for severe COVID-19. DM is highly prevalent in the general population. Defining strategies to reduce the health care system burden and the late arrival of some patients thus seems crucial. The study aim was to compare phenotypic characteristics between in and outpatients with diabetes and infected by COVID-19, and to build an easy-to-use hospitalization prediction risk score. This was a retrospective observational study. Patients with DM and laboratory- or CT-confirmed COVID-19, who did (n = 185) and did not (n = 159) require hospitalization between 10 March and 10 April 2020, were compared. Data on diabetes duration, treatments, glycemic control, complications, anthropometrics and peripheral oxygen saturation (SpO2) were collected from medical records. Stepwise multivariate logistic regressions and ROC analyses were performed to build the DIAB score, a score using no more than five easy-to-collect clinical parameters predicting the risk of hospitalization. The DIAB score was then validated in two external cohorts (n = 132 and n = 2036). Hospitalized patients were older (68.0 ± 12.6 vs. 55.2 ± 12.6 years, p < 0.001), with more class III obesity (BMI ≥ 40 kg/m2, 9.7 vs. 3.5%, p = 0.03), hypertension (81.6 vs. 44.3%, p < 0.0001), insulin therapy (37% vs. 23.7%, p = 0.009), and lower SpO2 (91.6 vs. 97.3%, p < 0.0001) than outpatients. Type 2 DM (T2D) was found in 94% of all patients, with 10 times more type 1 DM in the outpatient group (11.3 vs. 1.1%, p < 0.0001). A DIAB score > 27 points predicted hospitalization (sensitivity 77.7%, specificity 89.2%, AUC = 0.895), and death within 28 days. Its performance was validated in the two external cohorts. Outpatients with diabetes were found to be younger, with fewer diabetic complications and less severe obesity than inpatients. DIAB score is an easy-to-use score integrating five variables to help clinicians better manage patients with DM and avert the saturation of emergency care units.

This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in LMNA, c.1745G > T p.(Arg582Leu), and c.1892G> A p.(Gly631Asp), in two patients with early onset of diabetes mellitus, hypertriglyceridemia and non-alcoholic fatty liver disease. In these two patients, subcutaneous adipose tissue was persistent, at least on the abdomen, and the serum leptin level remained in the normal range. Cellular studies showed elevated nuclear anomalies, an accelerated senescence rate and a decrease of replication capacity in patient cells. In cellular models, the overexpression of mutated prelamin A phenocopied misshapen nuclei, while the partial reduction of lamin A expression in patient cells significantly improved nuclear morphology. Altogether, these results suggest a link between lamin A mutant expression and senescence associated phenotypes. Transcriptome analysis of the whole subcutaneous adipose tissue from the two patients and three controls, paired for age and sex using RNA sequencing, showed the up regulation of genes implicated in immunity and the down regulation of genes involved in development and cell differentiation in patient adipose tissue. Therefore, our results suggest that some mutations in LMNA are associated with severe metabolic phenotypes without subcutaneous lipoatrophy, and are associated with nuclear misshaping.

Motivation: The key structure for maintaining energy balance is the hypothalamus (HT), a small structure organized in multiple nuclei difficult to individualize with MR imaging. Goal(s): To study in vivo the modulation in Obesity and Anorexia Nervosa of morphometry and microstructure of HT nuclei involved in food networks. Approach: Characterization of T1 and volumes of HT nuclei (Neudorfer atlas) of 28 young women (13 Controls, 7 AN, 8O) using 3D-MP2RAGE 7T MRI. Results: Differences in T1 values and volumes were observed in Obese and AN in HT nuclei involved in food networks (bilateral AN, left PVN)Impact: Quantitative high resolution T1 MRI at 7T allows to characterize the morpho-structural modulation of HT nuclei involved in food networks in obesity and AN. These biomarkers may have a crucial role to monitor adaptation of food networks during therapeutic interventions.