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1. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Køber, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gøtze, Edi Prifti, Philippe Froguel, The MetaCardis Consortium, Jean-Daniel Zucker, Fredrik Bäckhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Blüher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clément, and Marc-Emmanuel Dumas

Subjects
Science
Abstract

Abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Published
2023
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2. Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients

Author

Etienne Charpentier, Alban Redheuil, Olivier Bourron, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Nadjia Kachenoura, Khaoula Bouazizi, Joe-Elie Salem, Guillaume Hekimian, Matthieu Kerneis, Zahir Amoura, Yves Allenbach, Stephane Hatem, Anne-Caroline Jeannin, Fabrizio Andreelli, Franck Phan, and COVID-19 APHP. SU Group

Subjects
Type 2 diabetes (T2D), Cardiac adipose tissue, Computed tomography, COVID-19, Mortality, Intensive care, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Keypoints Prognostic value of pericardiac fat tissue assessed using CT to predict adverse outcomes for T2D patients admitted for COVID-19 infection A disctinct phenotypic pattern was found between diabetic patients and controls with respect to adverse outcom:. classicl risk factors such as age or sex adetermine the prognosis in controls whereas the metabolic and inflammatory profile determine outcome in diabetics. Fast and reliable measurement of cardiac adipose tissue using CT. The assessment of this parameter could be useful to better stratify individual risk in diabetic patients with COVID-19 and adapt patient management of patients in routine practice.

Published
2022
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3. Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes

Author

Khaoula Bouazizi, Mohamed Zarai, Abdallah Noufaily, Mikaël Prigent, Thomas Dietenbeck, Emilie Bollache, Toan Nguyen, Valéria Della Valle, Eléonore Blondiaux, Karine Clément, Judith Aron-Wisnewsky, Fabrizio Andreelli, Alban Redheuil, and Nadjia Kachenoura

Subjects
epicardiac adipose tissue, cardiovascular MRI, type 2 diabetes, aortic flow, cardiometabolic disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundIt has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome.PurposeTo assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients.Materials and methodsThirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification.ResultsIn this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p

Published
2023
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4. Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

Author

Franck Phan, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Joe-Elie Salem, Nadjia Kachenoura, Khaoula Bouazizi, Etienne Charpentier, Yasmine Niati, Hasnae Bekkaoui, Zahir Amoura, Alexis Mathian, Olivier Benveniste, Patrice Cacoub, Yves Allenbach, David Saadoun, Jean-Marc Lacorte, Salma Fourati, Suzanne Laroche, Agnes Hartemann, Olivier Bourron, Fabrizio Andreelli, Alban Redheuil, and COVID-19 APHP.SU Group

Subjects
Cardiac computed tomography, Cardiac adipose tissue, Inflammation, Interleukin-6, COVID-19, Diabetes, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. Methods Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. Results Of the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p

Published
2021
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5. Regenerating islet-derived protein 3α: A promising therapy for diabetes. Preliminary data in rodents and in humans

Author

Aurélie Le Lay, Erwann Philippe, Fanny Roth, Ana Rodriguez Sanchez-Archidona, Florence Mehl, Jessica Denom, Rashmi Prasad, Olof Asplund, Ola Hansson, Mark Ibberson, Fabrizio Andreelli, Lyse Santoro, Paul Amouyal, Gilles Amouyal, Christian Brechot, Laure Jamot, Céline Cruciani-Guglielmacci, and Christophe Magnan

Subjects
Insulin resistance, Glucose uptake, Skeletal muscles, Type 2 diabetes, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.

Published
2022
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6. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, Eugeni Belda, Rima Chakaroun, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, Florian Marquet, Fabrizio Andreelli, Joe-Elie Salem, Karen Assmann, Jean-Philippe Bastard, Sofia Forslund, Emmanuelle Le Chatelier, Gwen Falony, Nicolas Pons, Edi Prifti, Benoit Quinquis, Hugo Roume, Sara Vieira-Silva, Tue H. Hansen, Helle Krogh Pedersen, Christian Lewinter, Nadja B. Sønderskov, The MetaCardis Consortium, Lars Køber, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Pilar Galan, Marc-Emmanuel Dumas, Jeroen Raes, Jean-Michel Oppert, Ivica Letunic, Jens Nielsen, Peer Bork, S. Dusko Ehrlich, Michael Stumvoll, Oluf Pedersen, Judith Aron-Wisnewsky, Karine Clément, and Fredrik Bäckhed

Subjects
Science
Abstract

Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Published
2020
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7. EPHX1 mutations cause a lipoatrophic diabetes syndrome due to impaired epoxide hydrolysis and increased cellular senescence

Author

Jeremie Gautheron, Christophe Morisseau, Wendy K Chung, Jamila Zammouri, Martine Auclair, Genevieve Baujat, Emilie Capel, Celia Moulin, Yuxin Wang, Jun Yang, Bruce D Hammock, Barbara Cerame, Franck Phan, Bruno Fève, Corinne Vigouroux, Fabrizio Andreelli, and Isabelle Jeru

Subjects
diabetes, genetics, epoxide hydrolase, adipocyte, cellular senescence, EPHX1, Medicine, Science, Biology (General), QH301-705.5
Abstract

Epoxide hydrolases (EHs) regulate cellular homeostasis through hydrolysis of epoxides to less-reactive diols. The first discovered EH was EPHX1, also known as mEH. EH functions remain partly unknown, and no pathogenic variants have been reported in humans. We identified two de novo variants located in EPHX1 catalytic site in patients with a lipoatrophic diabetes characterized by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analyses revealed that these variants led to the protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. CRISPR-Cas9-mediated EPHX1 knockout (KO) abolished adipocyte differentiation and decreased insulin response. This KO also promoted oxidative stress and cellular senescence, an observation confirmed in patient-derived fibroblasts. Metreleptin therapy had a beneficial effect in one patient. This translational study highlights the importance of epoxide regulation for adipocyte function and provides new insights into the physiological roles of EHs in humans.

Published
2021
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8. A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

Author

Chloé Amouyal, Julien Castel, Claudiane Guay, Amélie Lacombe, Jessica Denom, Stéphanie Migrenne-Li, Christine Rouault, Florian Marquet, Eleni Georgiadou, Theodoros Stylianides, Serge Luquet, Hervé Le Stunff, Raphael Scharfmann, Karine Clément, Guy A. Rutter, Olivier Taboureau, Christophe Magnan, Romano Regazzi, and Fabrizio Andreelli

Subjects
Diabetes, Bariatric surgery, Beta cell function, Insulin secretion, microRNA, ob/ob mouse, Medicine, Medicine (General), R5-920
Abstract

Background: Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods: We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca2+-imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings: EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation: Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding: European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Société Francophone du Diabète, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir.

Published
2020
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9. Diabetes Mellitus, Extreme Insulin Resistance, and Hypothalamic-Pituitary Langerhans Cells Histiocytosis

Author

Mathilde Sollier, Marine Halbron, Jean Donadieu, Ahmed Idbaih, Fleur Cohen Aubart, Corinne Vigouroux, Martine Auclair, Olivier Bourron, Marie Bastin, Géraldine Béra, Philippe Touraine, Jacques Young, Héléna Mosbah, Agnès Hartemann, Fabrizio Andreelli, and Chloé Amouyal

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background. Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm characterized by an infiltration of organs by Langerin + (CD207+) and CD1a+ histiocytes. Diabetes insipidus is a frequent manifestation of the disease, while diabetes mellitus is very rare. We report the first case of a 20-year-old man suffering from hypothalamopituitary histiocytosis and diabetes mellitus with serum anti-insulin receptor antibodies. Case Presentation. A 20-year-old patient was admitted for the evaluation of growth delay and hyperphagia. HbA1c level and fasting blood glucose were in the normal range. The diagnosis of hypothalamopituitary histiocytosis was based on histological features after biopsy of a large suprachiasmatic lesion identified on magnetic resonance imaging (MRI). Association of vinblastine and purinethol was started followed by a second-line therapy by cladribine. During the follow-up, the patient was admitted for recurrence of hyperglycemic states and extreme insulin resistance. The screening for serum anti-insulin receptor antibodies was positive. Each episode of hyperglycemia appeared to be correlated with tumoral activity and increase in serum anti-insulin receptor antibodies and appeared to be improved when the disease was controlled by chemotherapy. Conclusion. We report the first description of a hypothalamopituitary histiocytosis associated with serum anti-insulin receptor antibodies, extreme insulin resistance, and diabetes. Parallel evolution of glucose levels and serum anti-insulin receptor antibodies seemed to be the consequence of immune suppressive properties of cladribine.

Published
2019
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10. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, Eugeni Belda, Rima Chakaroun, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, Florian Marquet, Fabrizio Andreelli, Joe-Elie Salem, Karen Assmann, Jean-Philippe Bastard, Sofia Forslund, Emmanuelle Le Chatelier, Gwen Falony, Nicolas Pons, Edi Prifti, Benoit Quinquis, Hugo Roume, Sara Vieira-Silva, Tue H. Hansen, Helle Krogh Pedersen, Christian Lewinter, Nadja B. Sønderskov, The MetaCardis Consortium, Lars Køber, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Pilar Galan, Marc-Emmanuel Dumas, Jeroen Raes, Jean-Michel Oppert, Ivica Letunic, Jens Nielsen, Peer Bork, S. Dusko Ehrlich, Michael Stumvoll, Oluf Pedersen, Judith Aron-Wisnewsky, Karine Clément, and Fredrik Bäckhed

Subjects
Science
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.

Published
2020
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11. Increasing GLP-1 Circulating Levels by Bariatric Surgery or by GLP-1 Receptor Agonists Therapy: Why Are the Clinical Consequences so Different?

Author

Chloé Amouyal and Fabrizio Andreelli

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

The “incretin effect” is used to describe the observation that more insulin is secreted after the oral administration of glucose compared to that after the intravenous administration of the same amount of glucose. During the absorption of meals, the gut is thought to regulate insulin secretion by secreting a specific factor that targets pancreatic beta cells. Additional research confirmed this hypothesis with the discovery of two hormones called incretins: gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1). During meals, specific cells in the gut (L and K enteroendocrine cells) secrete incretins, causing an increase in the blood concentrations of, respectively, GLP-1 and GIP. Bariatric surgery is now proposed during the therapeutic management of type 2 diabetes in obese or overweight populations. It has been hypothesized that restoration of endogenous GLP-1 secretion after the surgery may contribute to the postsurgical resolution of diabetes. In 2005, the commercialization of GLP-1 receptor agonists gave the possibility to test this hypothesis. A few years later, it is now accepted that GLP-1 receptor agonists and bariatric surgery differently improve type 2 diabetes. These differences between endogenous and exogenous GLP-1 on glucose homeostasis emphasized the dual properties of GLP-1 as a peptide hormone and as a neurotransmitter.

Published
2016
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12. Differential pre-mRNA splicing regulates Nnat isoforms in the hypothalamus after gastric bypass surgery in mice.

Author

William R Scott, Cigdem Gelegen, Keval Chandarana, Efthimia Karra, Ahmed Yousseif, Chloé Amouyal, Agharul I Choudhury, Fabrizio Andreelli, Dominic J Withers, and Rachel L Batterham

Subjects
Medicine, Science
Abstract

Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling. Nnat is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin. Nnat pre-mRNA is differentially spliced to create Nnat-α and -β isoforms. Genetic variation of NNAT is associated with severe obesity. Currently, little is known about the long-term regulation of Nnat.Expression of Nnat isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery. Nnat expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of Nnat mRNA.Hypothalamic expression of both Nnat isoforms was comparably decreased by overnight and 24-h fasting. Nnat expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet. Nnat isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic Nnat-β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R(2) = 0.38, P = 0.01). In contrast, Nnat-α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R(2) = 0.06, P = 0.34). Hypothalamic expression of Nnat-β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery. Nnat expression was detected in brainstem, brown-adipose tissue, stomach and small intestine.Nnat expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery Nnat isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of Nnat pre-mRNA may contribute to weight-loss.

Published
2013
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13. The short-term prognosis of diabetic foot ulceration is independent of nutritional status at admission

Author

Florine Feron, Chloé Amouyal, Agnès Hartemann, Georges Ha Van, Olivier Bourron, Anne Dierick-Gallet, Caroline Michaux, Maude Dos Santos, Magali Baudot, Gaelle Devaux, Olivier Taboureau, and Fabrizio Andreelli

Subjects
Nursing (miscellaneous), Fundamentals and skills
Abstract

Diabetic foot ulcers are one of the complications of diabetes. Malnutrition is one of the risk factors for wounds but, on the other hand, diabetic foot ulceration may promote malnutrition. In this single-centre retrospective study we evaluated the frequency of malnutrition at first admission and the severity of foot ulceration. We demonstrated that malnutrition at admission correlated with duration of hospitalisation and with death rate rather than with the risk of amputation. Our data challenged the concept that protein-energy deficiency may worsen the prognosis of diabetic foot ulcers. Nevertheless, it is still important to screen nutritional status at baseline and during the follow-up in order to start specific nutritional support therapy as soon as possible in order to reduce morbidity/mortality related to malnutrition.

Published
2023

17. Insuline et dénutrition

Author

Romane Bertrand, Blandine Lambare, and Fabrizio Andreelli

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published
2022

18. Oral SGLT2 Inhibitors in Glycogen Storage Disease Type Ib and G6PC3-Deficiency. Preliminary Results from an Off-Label Study of 21 Patients

Author

Jean Donadieu, Aurelia Alimi, Anais Brassier, Blandine Beaupain, Camille Wicker, jean-Meidi Alili, Christine Bellanne-Chantelot, Amelie Chaussade, Martin Castelle, Mathlide Lamarque, Isabelle Plo, Lea Durix, Aude Pion, Sylvie Souquere, Caroline Marty, Pierre Simon Rohrlich, Karine Mention, Wadih Abouchahla, Marie Szymanowski, Myriam Dao, Felipe Suarez, Paola Parronchi, Boaz Palterer, Noemie Urvoy, Hélène Lapillonne, Fabrizio Andreelli, Emile Van Schaftingen, Philippe Labrune, Pascale De Lonlay, and Maria Veiga Da Cunha

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

19. Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real‐life experience from a national reference network

Author

Héléna Mosbah, Marie‐Christine Vantyghem, Estelle Nobécourt, Fabrizio Andreelli, Francoise Archambeaud, Elise Bismuth, Claire Briet, Maryse Cartigny, Benjamin Chevalier, Bruno Donadille, Anne Daguenel, Mathilde Fichet, Jean‐François Gautier, Sonja Janmaat, Isabelle Jéru, Carole Legagneur, Lysiane Leguier, Julie Maitre, Elise Mongeois, Christine Poitou, Eric Renard, Yves Reznik, Anne Spiteri, Florence Travert, Bruno Vergès, Jamila Zammouri, Corinne Vigouroux, Camille Vatier, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Adult, Leptin, Adolescent, Lipodystrophy, Endocrinology, Diabetes and Metabolism, Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Young Adult, Endocrinology, Lipodystrophy, Congenital Generalized, Internal Medicine, Humans, Retrospective Studies
Abstract

International audience; Aims: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromestreated with metreleptin in a national reference network, in a real-life setting.Patients and Methods: Clinical and metabolic data from patients receiving metreleptin in France wereretrospectively collected, at baseline, one year and at the latest follow-up during treatment.Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD, n=28) andpartial lipodystrophy (PLD, n=19) received metreleptin over the last decade. At baseline, age was 29.3[16.6-47.6] (years, median [interquartile range]); BMI 23.8 kg/m2 [21.2-25.7]; serum leptin 3.2 [1.0-4.9] ng/mL); 94% of patients had diabetes (66% insulin-treated), 53% hypertension, and 87%dyslipidemia. Metreleptin therapy, administered during 31.7 [14.2-76.0] months, was ongoing in 77%of patients at the latest follow-up. In patients with GLD, HbA1c (%) and fasting triglycerides (mmol/L)significantly decreased from baseline to one year-metreleptin treatment, from 8.4 [6.5-9.9] to 6.8 [5.6-7.4], and 3.6 [1.7-8.5] to 2.2 [1.1-3.7] respectively (p

Published
2022

20. Doubles-agonistes, tri-agonistes et multi-agonistes incrétines/glucagon

Author

Fabrizio Andreelli and Franck Phan

Subjects
Nutrition and Dietetics, business.industry, Endocrinology, Diabetes and Metabolism, Internal Medicine, Medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Resume L’innovation pharmacologique en diabetologie est un veritable defi. La nouvelle famille des co-agonistes des recepteurs GIP/GLP-1 represente une avancee therapeutique importante pour ameliorer la prise en charge du diabete de type 2 (DT2). L’activation des deux recepteurs incretines peut avoir des effets metaboliques additifs en comparaison a ceux obtenus avec les agonistes des recepteurs du GLP-1 seuls, en particulier sur la glycemie et l’exces de poids. Les etudes pre-cliniques, tout comme les essais chez l’homme, ont montre une amelioration de la glycemie a jeun et post-prandiale, de l’HbA1c, du poids, et du cholesterol total avec ces molecules. Les essais cliniques recents dans la population DT2 ont confirme ces donnees suggerant que les co-agonistes des recepteurs GIP/GLP-1 sont une innovation therapeutique.

Published
2021

21. Imagerie par résonance magnétique cardiovasculaire et ses applications dans la cardiomyopathie diabétique

Author

Alban Redheuil, Fabrizio Andreelli, Nadjia Kachenoura, and Khaoula Bouazizi-Verdier

Subjects
03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, 030218 nuclear medicine & medical imaging
Abstract

Resume L’imagerie par resonance magnetique (IRM) cardiovasculaire permet, grâce a ses incessantes innovations technologiques, de realiser une imagerie in vivo d’un cœur battant et d’une artere pulsatile avec une couverture anatomique et un contraste inegalables. Cette exploration peut etre realisee a l’etat de repos, mais egalement sous stress pharmacologique afin de detecter une maladie coronaire, souvent infraclinique, chez les patients diabetiques. Combinee a des methodes de traitement d’images avancees, elle permet egalement une analyse quantitative et multiparametrique du systeme cardiocirculatoire, en donnant acces a une mesure precise de sa geometrie et de sa fonction, ainsi qu’a ses caracteristiques tissulaires et metaboliques. L’alteration de ces biomarqueurs d’IRM dans la cardiomyopathie diabetique a un stade tres precoce, avant meme l’apparition des symptomes, en fait un examen determinant dans l’exploration de ces patients. En effet, la capacite de l’IRM a explorer finement l’alteration fonctionnelle du cœur et des vaisseaux associant une dysfonction contractile et une rigidite cardiaque a une rigidite aortique ou une atteinte microvasculaire et liees a des processus de fibrose et de surcharge lipidique permettent de decouvrir des atteintes restees meconnues et peuvent permettre de preciser le risque cardiovasculaire individuel chez les patients diabetiques.

Published
2021

22. Nutrition et insuffisance cardiaque

Author

Fabrizio Andreelli, Jean-Michel Lecerf, and Blandine Lambaré

Subjects
03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine
Abstract

Resume L’insuffisance cardiaque est une pathologie dont la mortalite reste elevee. L’insuffisance cardiaque peut se compliquer d’une denutrition qui est un facteur independant de mortalite et un facteur precipitant l’aggravation de l’atteinte cardiaque. De nombreux mecanismes sont en jeu dans la survenue de la denutrition, parmi lesquels, l’âge, la demence, la polymedication, l’inflammation chronique, la carence martiale, l’œdeme de la paroi intestinale et un desequilibre de la flore intestinale. Le depistage de la denutrition dans la population de patients insuffisants cardiaques pourrait permettre une prise en charge nutritionnelle qui pourrait ameliorer le pronostic de cette population.

Published
2021

23. Quelles tendances pour les techniques mini-invasives de chirurgie bariatrique ?

Author

Fabrizio Andreelli and Marie Bastin

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract

Resume Si les techniques de chirurgie bariatrique ont prouve leur efficacite pour le controle ponderal et du diabete de type 2 (DT2) sur le moyen terme, le risque anesthesique et le refus possible des patients a conduit a proposer des alternatives non chirurgicales de controle ponderal et du DT2. Comme la chirurgie, celles-ci reduisent le volume de l'estomac ou limitent le contact entre l'epithelium intestinal et les aliments. Ces techniques nouvelles utilisent le plus souvent la voie endoscopique, alors que se developpent des methodes ou le dispositif est ingere par voie orale sous forme d'une gelule de la taille d'un medicament. Moins efficaces en absolu sur le plan ponderal que la chirurgie bariatrique, ces methodes doivent neanmoins encore etre validees sur le moyen/long terme et sur leur morbidite.

Published
2019

24. Characteristics of insulinopenic and non insulinopenic diabetes related to immune checkpoint inhibitors: A French pharmacovigilance study

Author

Marion Allouchery, Kevin Bihan, Bénédicte Lebrun-Vignes, Franck Rouby, Marie Bastin, Pirayeh Eftekhari, Marion Sassier, Fabrizio Andreelli, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Ipilimumab, Type 2 diabetes, Pembrolizumab, 030226 pharmacology & pharmacy, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Pharmacology (medical), Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, Ketoacidosis, Nivolumab, Diabetes Mellitus, Type 2, business, Adverse drug reaction, medicine.drug
Abstract

Summary Introduction Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is an immune-related adverse drug reaction (irADR). Hyperglycemia can be linked to endogenous insulin deficiency with ketoacidosis or associated with preserved beta-cell function. Objectives We aimed to identify the characteristics of both types of ICI-DM (type 1 and type 2 DM), to improve our understanding of this irADR and its management. Methods Data for ICI-DM recorded in the French Pharmacovigilance Database from 2015 to October 2019 were analyzed according to the French causality assessment. Results In total, 60 subjects were included. Anti-PD1/PDL1 pathway blockade therapy (nivolumab: 61.7% + 3.3% in association with ipilimumab pembrolizumab: 28.3%) was most frequently implicated in ICI-DM, but some reports involved anti-CTLA4 drug (ipilimumab: 6.7% + 3.3% in association with nivolumab). One third of reports occurred within one month of the initiation of immunotherapy. Decreased insulin secretion (defined by the presence of ketone bodies) were confirmed in 80% of reports. Among them, 54% of patients met the diagnostic criteria for fulminant diabetes. Overall, 17.7% of the reports had pre-existing type 2 diabetes T2D. Four deaths due to hyperglycemia were declared, with altered insulin secretion in only two of these reports. BMI was lower in the insulinopenic group (23.4 ± 0.7 vs. 27.9 ± 1.6, P = 0.004) and other irADRs were more frequently observed in patients with persistent insulin secretion (66.7 vs. 18.8%, P = 0.02). We found no difference in age, indication or cumulative ICI dose between the two groups (with and without insulinopenia). The presence of GAD antibodies was associated with a shorter time to diabetes onset (42.6 ± 6.1 vs. 208.1 ± 41.6 days, P = 0.029). Conclusions ICI-DM is a rare but serious irADR triggered by all classes of immunotherapy. The observation period for ICI-DM can be shortened for patients positive for anti-GAD antibodies. Endogenous insulin deficiency did not appear to be the only mechanism involved in ICI-DM, as beta-cell function was preserved in 20% of reports. Improvements in our understanding of this complication will be required for its prevention.

Published
2021

25. HNF4g invalidation prevents diet-induced obesity via intestinal lipid malabsorption

Author

Eva Gil-Iturbe, Agnès Ribeiro, Céline Osinski, Léa Le Gléau, Sami Ayari, Patricia Serradas, Karine Clément, Hédi Soula, Nathalie Kapel, Armelle Leturque, Fabrizio Andreelli, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, medicine.medical_specialty, obesity, Calorie, Malabsorption, Nutrition and HNF-4gamma, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Fructose, Biology, Diet, High-Fat, Weight Gain, high-fat/high fructose diet, Energy homeostasis, Jejunum, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Malabsorption Syndromes, Internal medicine, Glucose Intolerance, medicine, Glucose homeostasis, Animals, intestine, Cells, Cultured, Triglycerides, 030304 developmental biology, 2. Zero hunger, Mice, Knockout, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lipid malabsorption, medicine.disease, Lipid Metabolism, SCARB1, Intestines, Mice, Inbred C57BL, medicine.anatomical_structure, Hepatocyte Nuclear Factor 4, Intestinal Absorption, Female, GLP-1, Gene Deletion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lipoprotein
Abstract

Changes in dietary habits have occurred concomitantly with a rise of type 2 diabetes (T2D) and obesity. Intestine is the first organ facing nutrient ingestion and has to adapt its metabolism with these dietary changes. HNF-4γ, a transcription factor member of the nuclear receptor superfamily and mainly expressed in intestine, has been suggested to be involved in susceptibility to T2D. Our aim was to investigate the role of HNF-4γ in metabolic disorders and related mechanisms. Hnf4g−/− mice were fed high-fat/high-fructose (HF-HF) diet for 6 weeks to induce obesity and T2D. Glucose homeostasis, energy homeostasis in metabolic cages, body composition and stool energy composition, as well as gene expression analysis in the jejunum were analyzed. Despite an absence of decrease in calorie intake, of increase in locomotor activity or energy expenditure, Hnf4g−/− mice fed with HF-HF are protected against weight gain after 6 weeks of HF-HF diet. We showed that Hnf4g−/− mice fed HF-HF display an increase in fecal calorie loss, mainly due to intestinal lipid malabsorption. Gene expression of lipid transporters, Fatp4 and Scarb1 and of triglyceride-rich lipoprotein secretion proteins, Mttp and ApoB are decreased in gut epithelium of Hnf4g−/− mice fed HF-HF, showing the HNF-4γ role in intestine lipid absorption. Furthermore, plasma GLP-1 and jejunal GLP-1 content are increased in Hnf4g−/− mice fed HF-HF, which could contribute to the glucose intolerance protection. The loss of HNF-4γ leads to a protection against a diet-induced weight gain and to a deregulated glucose homeostasis, associated with lipid malabsorption.

Published
2021

26. Intestinal alteration of α-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission

Author

Léa, Le Gléau, Christine, Rouault, Céline, Osinski, Edi, Prifti, Hédi Antoine, Soula, Jean, Debédat, Pauline, Busieau, Chloé, Amouyal, Karine, Clément, Fabrizio, Andreelli, Agnès, Ribeiro, and Patricia, Serradas

Subjects
Male, Mice, Inbred C57BL, Diabetes Mellitus, Type 2, Enteroendocrine Cells, Taste, Animals, Dysbiosis, Humans, Obesity, Transducin, Gastrointestinal Microbiome, Signal Transduction
Abstract

Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EECs). This receptor is coupled to the gustducin G-protein, which α-subunit is encoded by

Published
2021

28. New roles for prokineticin 2 in feeding behavior, insulin resistance and type 2 diabetes: Studies in mice and humans

Author

Ewout Foppen, Frédéric Fumeron, Mylène Vincent, Mireia Montaner, Ronan Roussel, Marie Mortreux, Raphaël G. P. Denis, Christophe Magnan, Michel Marre, Fabrizio Andreelli, Nadim Kassis, Margaux Kujawski-Lafourcade, Stéphanie Migrenne-Li, Jessica Denom, Hirac Gurden, Beverley Balkau, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Cochin (UMR_S567 / UMR 8104), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Endocrinology Laboratory, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Institut national de recherches archéologiques préventives (Inrap), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, 0301 basic medicine, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Type 2 diabetes, Energy homeostasis, Eating, Mice, 0302 clinical medicine, Food intake, Medicine, RNA, Small Interfering, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Olfactory Bulb, Metabolic syndrome, Recombinant Proteins, Original Article, Female, RNA Interference, Adult, lcsh:Internal medicine, medicine.medical_specialty, 030209 endocrinology & metabolism, Carbohydrate metabolism, Polymorphism, Single Nucleotide, Gastrointestinal Hormones, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, Animals, Humans, lcsh:RC31-1245, Molecular Biology, Aged, business.industry, Neuropeptides, Feeding Behavior, Cell Biology, medicine.disease, Obesity, Main olfactory bulb, Meal pattern, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Prokineticin 2, Energy Metabolism, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Body mass index
Abstract

Objective Prokineticin 2 (PROK2) is a hypothalamic neuropeptide that plays a critical role in the rhythmicity of physiological functions and inhibits food intake. PROK2 is also expressed in the main olfactory bulb (MOB) as an essential factor for neuro-and morphogenesis. Since the MOB was shown to be strongly involved in eating behavior, we hypothesized that PROK2 could be a new target in the regulation of food intake and energy homeostasis, through its effects in the MOB. We also asked whether PROK2 could be associated with the pathophysiology of obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2D) in humans. Methods We assessed in wild type mice whether the expression of Prok2 in the MOB is dependent on the nutritional status. We measured the effect of human recombinant PROK2 (rPROK2) acute injection in the MOB on food intake and olfactory behavior. Then, using a lentivirus expressing Prok2-shRNA, we studied the effects of Prok2 underexpression in the MOB on feeding behavior and glucose metabolism. Metabolic parameters and meal pattern were determined using calorimetric cages. In vivo 2-deoxyglucose uptake measurements were performed in mice after intraperitoneally insulin injection. Plasmatic PROK2 dosages and genetic associations studies were carried out respectively on 148 and more than 4000 participants from the D.E.S.I.R. (Data from an Epidemiologic Study on the Insulin Resistance Syndrome) cohort. Results Our findings showed that fasting in mice reduced Prok2 expression in the MOB. Acute injection of rPROK2 in the MOB significantly decreased food intake whereas Prok2-shRNA injection resulted in a higher dietary consumption characterized by increased feeding frequency and decreased meal size. Additionally, Prok2 underexpression in the MOB induced insulin resistance compared to scrambled shRNA-injected mice. In the human D.E.S.I.R. cohort, we found a significantly lower mean concentration of plasma PROK2 in people with T2D than in those with normoglycemia. Interestingly, this decrease was no longer significant when adjusted for Body Mass Index (BMI) or calorie intake, suggesting that the association between plasma PROK2 and diabetes is mediated, at least partly, by BMI and feeding behavior in humans. Moreover, common Single Nucleotide Polymorphisms (SNPs) in PROK2 gene were genotyped and associated with incident T2D or impaired fasting glycemia (IFG), MetS, and obesity. Conclusions Our data highlight PROK2 as a new target in the MOB that links olfaction with eating behavior and energy homeostasis. In humans, plasma PROK2 is negatively correlated with T2D, BMI, and energy intake, and PROK2 genetic variants are associated with incident hyperglycemia (T2D/IFG), the MetS and obesity., Highlights • Fasting alters prokineticin 2 (Prok2) expression in the main olfactory bulb (MOB). • Acute injection of PROK2 into the MOB diminishes food intake. • Partial deletion of MOB-Prok2 affects meal pattern and induces insulin resistance. • Type 2 diabetes (T2D) in humans is correlated with lower plasma PROK2 level. • Polymorphisms of PROK2 gene associate with incident T2D and the metabolic syndrome.

Published
2019

29. Dual GIP–GLP1-Receptor Agonists In The Treatment Of Type 2 Diabetes: A Short Review On Emerging Data And Therapeutic Potential

Author

Marie Bastin and Fabrizio Andreelli

Subjects
Pharmacology, business.industry, Type 2 Diabetes Mellitus, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease, Obesity, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Postprandial, Internal Medicine, medicine, Metabolic syndrome, Receptor, business, Dyslipidemia
Abstract

The need for efficient and safe therapy to improve such metabolic diseases as obesity and type 2 diabetes mellitus is currently unmet. The development of dual GIPR-GLP1R coagonists that bind to either one or the other receptor (sequence-mixed dual agonists) has emerged as an innovative therapeutic strategy for obesity and type 2 diabetes. Combined activation of both receptors may act synergistically providing additive effects on glucose and body weight in comparison of GLP1 analogues alone. Preclinical studies have confirmed that GIPR-GLP1R coagonists improve several hallmarks of metabolic syndrome, such as obesity, hyperglycemia, and dyslipidemia. These metabolic benefits have been translated from mice to nonhuman primates and humans. Recent clinical trials have shown that coagonists induce significant benefits on body weight, fasting, and postprandial glucose levels, insulin sensitivity, and total cholesterol. Combined GIP- and GLP1R activators have the potential to become a treatment option for patients with type 2 diabetes.

Published
2019

30. Indications thérapeutiques et effets métaboliques de la métréleptine chez les patients atteints de lipodystrophie : données de vie réelle du registre français

Author

J.F. Gautier, A. DaguenelNguyen, M. Fichet, J. Maitre, Yves Reznik, E. Bismuth, Corinne Vigouroux, F. Travert, A. Spiteri, Eric Renard, Camille Vatier, Sonja Janmaat, Claire Briet, J. Zammouri, A. Guilleux, C. Legagneur, M. Cartigny, Marie-Christine Vantyghem, E. Mongeois, Héléna Mosbah, B. Donadille, Christine Poitou, F. Archambeaud, Isabelle Jéru, Fabrizio Andreelli, B. Vergès, and E. Nobecourt

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, General Medicine
Published
2021

31. The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury and/or proteinuria

Author

David Buob, Ap-Hp, Renaud Snanoudj, Matthieu Jamme, Marie-Christine Verpont, Guillaume Geri, Nicolas Pallet, Christian Richard, Olivia May, Hélène François, Thomas Sthelé, Arthur Michon, Xavier Belenfant, Anne Grunenwald, Vincent Audard, Ziad A. Massy, Anissa Moktefi, François Gaillard, Christophe Legendre, Mohamad Zaidan, Fabrizio Andreelli, Julie Oniszczuk, Ophelie Le Monnier, Hassane Izzedine, Charlotte Mussini, Hélène Dobosziewicz, Albane Brodin-Sartorius, Universities, Marie Essig, Edouard Lefèvre, Zahir Amoura, Manon Dekeyser, Sophie Ferlicot, Aurélie Sannier, Alexis Mathian, Aymeric Couturier, Eric Daugas, Matthieu Guillet, Romain Arrestier, Isabelle Brocheriou-Spelle, Camille Petit-Hoang, and Nadine Maroun

Subjects
kidney, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Diabetes mellitus, Internal medicine, medicine, Renal replacement therapy, AcademicSubjects/MED00340, Dialysis, focal segmental glomerulosclerosis, Kidney, Transplantation, collapsing glomerulopathy, medicine.diagnostic_test, business.industry, Acute kidney injury, COVID-19, Fast Track Original Article, medicine.disease, acute tubular injury, medicine.anatomical_structure, Nephrology, Renal biopsy, business
Abstract

Background The coronavirus disease 2019 (COVID-19) may be associated with kidney injury, which may impact patient's prognosis. Methods We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury (AKI) and/or proteinuria and underwent a kidney biopsy in Paris and its metropolitan area. Results Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between 8 March and 19 May 2020 were included. The median age was 63 years (interquartile range 52–69). Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney disease (25.5%), cardiac diseases (38.6%) and respiratory diseases (27.3%). Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%) and diarrhoea (23.4%). Almost all patients developed AKI (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy (CG) and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while 8 (17%) had an alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and CG was only observed in patients harbouring a combination of APOL1 risk variants. At the last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 had died. Conclusions This study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Published
2021
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32. Massive lactic acidosis and ketoacidosis with glucagon deficiency in a chronic alcoholic patient

Author

Patrick Gilon, Philippe Boudou, Fabrizio Andreelli, Michel Djibré, Pascal Ferré, Soraya Fellahi, Fidaa Ibrahim, Mathieu Boissan, and UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition

Subjects
2. Zero hunger, 0303 health sciences, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Chronic alcoholic, 030209 endocrinology & metabolism, General Medicine, medicine.disease, Glucagon Deficiency, Gastroenterology, 3. Good health, Ketoacidosis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Lactic acidosis, Internal Medicine, medicine, business, 030304 developmental biology
Abstract

A non-diabetic chronic alcoholic and undernourished male patient [body mass index (BMI): 16.6 kg/m2] was admitted to our hospital emergency department. He had fasted for the previous 3 days. His blood lactate and ketone body concentrations were massively elevated (18 mmol/L and 14 mmol/L, respectively). Ethanolaemia was negative. Massive metabolic acidosis was noted with a pH of 7.04. Renal function remained normal, but there was mild hepatocellular deficiency and no acute pancreatitis. The patient was hypoglycaemic at admission with a blood glucose level of 3.0 mmol/L, and low concentrations of insulin, C-peptide and insulin-like growth factor (IGF)-1, as well as very low glucagon concentrations (5.2 ng/L; normal range: 8–74 ng/L) despite the prevailing glycaemia. In contrast, cortisol, sex hormone-binding globulin (SHBG) and growth hormone (GH) concentrations were elevated. [...]

Published
2021

33. Collaborateurs

Author

Amar Abderrhamani, Najate Achamrah, Benjamin Allès, Maud Alligier, Chloé Amouyal, Sébastien André, Fabrizio Andreelli, Barbara Antuna-Puente, Gérard Apfeldorfer, Roberto Arienzo, Isabelle Arnulf, Judith Aron-Wisnewski, Estelle Aubry, Antoine Avignon, Anne Bachelot, Pascal Barat, Robert Barouki, Jean-Philippe Bastard, Marie Bastin, Thibaut Batisse, Bernard Bauduceau, Catherine Bauters, Pierre Bel Lassen, Alice Bellicha, Audrey Bergouignan, Rebecca Bienvenot, Philip Böhme, Amélie Bonnefond, Lyse Bordier, Yves Boirie, Anne-Laure Borel, Philippe Bouchard, Jean-Luc Bouillot, Marie-Christine Boutron-Ruault, Édith Brot-Laroche, Robert Caiazzo, Claire Carette, Caroline Carriere, Audrey Carriere-Pazat, Louis Casteilla, Dominique-Adèle Cassuto, Marie-Aline Charles, Didier Chapelot, Hélène Charreire, Nicolas Chevalier, Jean-Marc Chevallier, Cécile Ciangura, Karine Clément, Moïse Coëffier, Philippe Cornet, Christine Cortet, Muriel Coupaye, Sébastien Czernichow, Jérôme Dargent, Nathalie Delzenne, Philippe Deruelle, Jean-Claude Desport, Magalie Desseigne, Bruno Detournay, Sébastien Dharancy, Emmanuel Disse, Bruno Donadille, Claire Douillard, Béatrice Dubern, Sophie Dubreuil, Martine Duclos, Hélène Duez, Sophie Dunoyer, Charlotte Dupont, Vincent Durlach, Dominique Durrer-Schutz, Sophie Duverne, Harold Eburdery, Stéphanie Espiard, Nathalie Esser, Amandine Everard, Pauline Faucher, Philippe Fayemendy, Soraya Fellahi, Bruno Fève, Alicia Fillon, Vanessa Folope, Isabelle Fontanille, Marie-Laure Frelut, Philippe Froguel, Bénédicte Gaborit, Blandine Gatta-Cherifi, Christelle Guillet, Laurent Grange, Catherine Grangeard, Iva Gueorguieva, Serge Halimi, Hélène Hanaire, Solveig Heide, Barbara Heude, Sylvain Iceta, Sonja Janmaat, Isabelle Jéru, Pierre Jésus, Anne-Sophie Joly, Béatrice Jouret, Chantal Julia, Sabrina Julien-Sweerts, Min Ji Kim, Miriam Ladsous, Jean-Daniel Lalau, Dominique Langin, Olivier Lascols, Guillaume Lassailly, Claire de La Serre, Martine Laville, Sophie Laye, Jean-Michel Lecerf, Armelle Leturque, Rachel Lévy, Yasmine Lienard, Guillaume Losserand, Aïcha Maghroudi, Christophe Magnan, Geneviève Marcelin, Camille Marciniak, Philippe Marre, Lucile Marty, Philippe Mathurin, Joane Matta, Matthieu Mencia-Huerta, Andréanne Michaud, Vincent Miramont, Caroline Mocquot, Sandrine Monnery-Patris, Émilie Montastier, Pauline Morigny, Héléna Mosbah, Nathalie Negro, Audrey Neyrinck, Jean-Michel Oppert, Naïma Oukhouya Daoud, Filippo Pacini, Julien Paccou, Nicolas Paquot, François Pattou, Soazig Péron-Le Lay, Pierre Peuteuil, Tigran Poghosyan, Christine Poitou, Jean-Pierre Poulain, Guillaume Pourcher, Didier Quilliot, Jocelyne Raison, Marc Raucoules-Aimé, Gérard Ribes, Nathalie Rigal, Patrick Ritz, Claire Rives-Lange, Pauline Riviere, Maud Robert, Julie Rodriguez, Monique Romon, Cindy Rose, Romain Rozier, Thibault de Saint Pol, Frédéric Sanguignol, André Scheen, Jean-Louis Schlienger, Nathalie Sermondade, Yasmine Sebti, Chantal Simon, Luc Tappy, Maïté Tauber, Hélène Thibault, David Thivel, Philippe Valet, Marie-Christine Vantyghem, Camille Vatier, Bruno Verges, Hélène Verkindt, Bernard Vialettes, Corinne Vigouroux, Stéphane Walrand, Bernard Waysfeld, Jamila Zammouri, Jean-Philippe Zermati, Olivier Ziegler, and Jean-Daniel Zucker

Published
2021

34. Toxicités sévères immuno-induites par les inhibiteurs de points de contrôle immunitaire : implications pour le réanimateur

Author

Anne Bachelot, Kevin Bihan, Mathieu Kerneis, Marie Bastin, Yves Allenbach, Thierry Maisonobe, Fabrizio Andreelli, Stéphane Ederhy, Jean-Philippe Spano, Aurore Vozy, Jacques Cadranel, Jean-Baptiste Bachet, A. Canellas, Sarah Leonard Louis, Joe-Elie Salem, Corinne Isnard Bagnis, Dominique Thabut, Bénédicte Lebrun Vignes, Lee S. Nguyen, Nicolas Weiss, Baptiste Hervier, Charlotte Fenioux, Dimitri Psimaras, Nicolas Bréchot, Sylvain Choquet, Céline Anquetil, and Adam Celier

Subjects
medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, Cancer, Emergency Nursing, Multidisciplinary team, medicine.disease, Intensive care unit, law.invention, law, Multidisciplinary approach, Intensive care, Emergency Medicine, medicine, In patient, Intensive care medicine, business, Adverse effect
Abstract

Depuis la révolution de l’immunothérapie utilisant les inhibiteurs de points de contrôle immunitaire dans la prise en charge de nombreux cancers, les oncologues font face à de nouveaux types de toxicités dites immuno-induites. La compréhension de leurs mécanismes et la mise en place de recommandations claires sont les clés de leur prise en charge. La gravité potentielle de ces toxicités et la très nette amélioration du pronostic apportée par ces traitements pour les patients porteurs de cancers métastatiques rend le rôle du réanimateur primordial. Le but de cette mise au point est d’effectuer une synthèse des toxicités immuno-induites pouvant conduire les patients en cours de traitement par inhibiteur de points de contrôle immunitaireen réanimation et ainsi de proposer des recommandations dans leur prise en charge afin d’aider le réanimateur dans sa démarche diagnostique et thérapeutique. L’imbrication de toxicités immuno-induites pouvant toucher plusieurs organes de façon concomitante, impose une prise en charge pluridisciplinaire regroupant oncologue, spécialiste d’organes et réanimateur. La mise en place de réunion de concertation pluridisciplinaire dédiée à ce type de toxicités permet ce regroupement, de même que le développement d’une expertise commune au sein d’un centre, la création de protocoles de soins et de recherche dédiés à la compréhension et la prise en charge de ces toxicités, et ce afin d’optimiser la gestion de ces patients.

Published
2020

35. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Ivica Letunic, Pilar Galan, Karen E. Assmann, Gwen Falony, Nicolas Pons, Fredrik Bäckhed, Trine Nielsen, Per-Olof Bergh, Lars Køber, Jens Nielsen, S. Dusko Ehrlich, Eugeni Belda, Henrik Vestergaard, Edi Prifti, Florian Marquet, Marc-Emmanuel Dumas, Jean-Michel Oppert, Michael Stumvoll, Sara Vieira-Silva, Pierre Bel Lassen, Jeroen Raes, Helle Krogh Pedersen, Judith Aron-Wisnewsky, Torben Hansen, Antonio Molinaro, Peer Bork, Oluf Pedersen, Christine Rouault, Benoit Quinquis, Christian Lewinter, Joe-Elie Salem, Rima Chakaroun, Tue H. Hansen, Fabrizio Andreelli, Hao Wu, Nadja B Sønderskov, Solia Adriouch, Sébastien André, Karine Clément, Jean-Daniel Zucker, Marcus Henricsson, Hugo Roume, Sofia K. Forslund, Jean-Philippe Bastard, University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Universität Leipzig, University of Copenhagen = Københavns Universitet (UCPH), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), VIB-KU Leuven Center for Microbiology [Leuven, Belgium], Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Biobyte Solutions GMBH, Chalmers University of Technology [Gothenburg, Sweden], European Molecular Biology Laboratory [Heidelberg] (EMBL), Universität Heidelberg [Heidelberg] = Heidelberg University, MetaCardis Consortium: Renato Alves, Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Olivier Barthelemy, Jean-Paul Batisse, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Julien Chilloux, Cecile Ciangura, Luis Pedro Coelho, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Leopold Fezeu, Sebastien Fromentin, Philippe Giral, Jens Peter Gøtze, Agnes Hartemann, Jens Juul Holst, Serge Hercberg, Gerard Helft, Malene Hornbak, Jean-Sebastien Hulot, Richard Isnard, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Nadja Buus Kristensen, Michael Kuhn, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moutel, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Sebastien Schmidt, Lucas Moitinho-Silva, Johanne Silvain, Nataliya Sokolovska, Sothea Touch, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., Lesnik, Philippe, Universität Leipzig [Leipzig], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Universität Heidelberg [Heidelberg]

Subjects
Multidisciplinary, Imidazole propionate, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, Pharmacology, Biology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, [SDV] Life Sciences [q-bio], Microbial ecology, Diabetes mellitus, medicine
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.

Published
2020

36. Dietary Assessment in the MetaCardis Study: Development and Relative Validity of an Online Food Frequency Questionnaire

Author

Karine Clément, Eric Bruckert, Torben Hansen, Tatjana Schütz, Matthias Blüher, Trine Nielsen, Agnes Harteman, Gérard Helft, Lars Køber, Jean-Michel Oppert, Henrik Vestergaard, Fabien Delaere, Eric O. Verger, Patrice Armstrong, Nicolas Gausserès, Jean-Sébastien Hulot, Bridget A. Holmes, Philippe Giral, Judith Aron-Wisnewsky, Xavier Girerd, Michael Stumvoll, Rima Chakaroun, Oluf Pedersen, Christine Poitou, Fabrizio Andreelli, Gilles Montalescot, Richard Isnard, Rikke J Gøbel, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Danone Nutricia Research [Palaiseau, France], Centre Daniel Carasso [Palaiseau, France], University of Copenhagen = Københavns Universitet (UCPH), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MetaCardis Consortium: Fabrizio Andreelli, Matthias Bluher, Eric Bruckert, Philippe Giral, Xavier Girerd, Torben Hansen, Agnes Harteman, Gérard Helft, Jean-Sébastien Hulot, Richard Isnard, Lars Køber, Gilles Montalescot, Jean-Michel Oppert, Christine Poitou, Oluf Pedersen, Michael Stumvoll, Henrik Vestergaard, Universität Leipzig [Leipzig], and Lesnik, Philippe

Subjects
Male, 0301 basic medicine, Gerontology, Food intake, Dietary assessment, Denmark, [SDV]Life Sciences [q-bio], Portion sizes, Self Administration, Portion size, EPIC, Body Mass Index, Food group, Germany, Surveys and Questionnaires, Medicine, Prospective Studies, Relative validity, Nutrition and Dietetics, food and beverages, Food frequency questionnaire, General Medicine, Middle Aged, Micronutrient, [SDV] Life Sciences [q-bio], Fatty Acids, Unsaturated, Female, Dietary Proteins, France, Adult, Development, 03 medical and health sciences, Environmental health, Dietary Carbohydrates, Humans, MetaCardis study, Aged, Internet, 030109 nutrition & dietetics, business.industry, Portion Size, Reproducibility of Results, Dietary Fats, Diet, Cross-Sectional Studies, Nutrition Assessment, Mental Recall, business, Food Science
Abstract

International audience; Background: The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet-disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study.Objective: The objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study-one FFQ per country-and to assess the relative validity of the French MetaCardis FFQ.Design: The layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized.Participants/setting: The validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France.Main outcome measures: Food intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs).Statistical analyses performed: Several measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses.Results: The French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex.Conclusions: The French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.

Published
2017

37. Incretin response in immune checkpoint inhibitor-induced diabetes: an observational study

Author

Emmanuelle Kuhn, Jean Philippe Spano, Samy Chelabi, Marie Bastin, Fabrizio Andreelli, Aurelie Villemain, Olivier Taboureau, Jordan J Wright, Anne Toulgoat, Pauline Busieau, and Christine Rouault

Subjects
Dipeptidyl-Peptidase IV Inhibitors, business.industry, Endocrinology, Diabetes and Metabolism, Immune checkpoint inhibitors, MEDLINE, Incretin, General Medicine, Bioinformatics, medicine.disease, Incretins, Glucagon-Like Peptide-1 Receptor, Endocrinology, Diabetes Mellitus, Type 2, Diabetes mellitus, Internal Medicine, Medicine, Humans, Observational study, business, Immune Checkpoint Inhibitors
Published
2020

38. A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

Author

Olivier Taboureau, Florian Marquet, Chloé Amouyal, Julien Castel, Christine Rouault, Hervé Le Stunff, Theodoros Stylianides, Karine Clément, Raphael Scharfmann, Eleni Georgiadou, Amélie Lacombe, Guy A. Rutter, Romano Regazzi, Christophe Magnan, Claudiane Guay, Fabrizio Andreelli, Jessica Denom, Stéphanie Migrenne-Li, Serge Luquet, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Imperial College London, Loughborough University, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Nanyang Technological University [Singapour], Service de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Wellcome Trust, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Lausanne = University of Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
0301 basic medicine, medicine.medical_specialty, endocrine system, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Bariatric Surgery, lcsh:Medicine, Inflammation, Type 2 diabetes, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, ob/ob mouse, General Biochemistry, Genetics and Molecular Biology, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, media_common.cataloged_instance, Medicine [Science], European union, media_common, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Bariatric surgery, geography, lcsh:R5-920, geography.geographical_feature_category, microRNA, business.industry, Insulin secretion, Diabetes, lcsh:R, 1103 Clinical Sciences, Beta cell function, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Islet, 3. Good health, Surgery, 030104 developmental biology, Lipotoxicity, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Beta cell, medicine.symptom, business, lcsh:Medicine (General)
Abstract

Background Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca2+-imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Societe Francophone du Diabete, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir.

Published
2020

39. 1064-P: The Human Recombinant REG3A Protein ALF-5755 Restores Glucose Homeostasis and Insulin Sensitivity in High-Fat Fed Mice and in Ob/Ob Mice

Author

Gilles Amouyal, Paul Amouyal, Christophe Magnan, Marion Darnaud, Christian Bréchot, Patrick Gonzalez, Laure Jamot, Céline Cruciani-Guglielmacci, Jamila Faivre, Nicolas Moniaux, and Fabrizio Andreelli

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Glucose uptake, digestive, oral, and skin physiology, AMPK, Skeletal muscle, medicine.disease, Endocrinology, Insulin resistance, medicine.anatomical_structure, Basal (medicine), Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Glucose homeostasis, Glycolysis, business
Abstract

Introduction: REG3A (Regenerating islet-derived protein 3A) is a carbohydrate-binding protein belonging to the family of C-type lectins. REG3A has antioxidant and anti-inflammatory properties modulating glucose and lipid homeostasis. We report a study of the effects of the administration of the human recombinant REG3A protein ALF-5755 on glucose and lipid homeostasis in insulin-resistant mice. Materials and Methods: 4-week-old C57Bl/6N male mice were fed HFD for 12 weeks. The control group received a standard chow diet. 12-week-old Ob/Ob mice were used. Mice were given ALF-5755 (43µg/day, ALF group) or a formulation buffer (buffer group) by subcutaneous infusion for 28 days. We measured: body weight, blood glucose, fasting insulin, glucose tolerance and insulin sensitivity, glucose turnover and uptake during hyperinsulinemic/euglycemic clamps and AMPK activity. Results: In both models, ALF-5755 administration significantly decreased basal blood glucose with no change in basal insulin levels. The changes in blood glucose levels in response to an oral glucose load in the ALF and buffer groups were similar in HFD-fed mice but were lowered by ALF-5755 in Ob/Ob mice. Insulin secretion at 15 and 30 min was significantly reduced in the ALF group compared to Buffer group in both models. During clamp, glycolytic muscles exhibited an increase in glucose uptake in HFD-fed mice, and an increase in AMPK activity in both models treated with ALF-5755. Insulin sensitivity was increased in ALF group. The plasma TG was significantly decreased in the ALF compared to Buffer group. No difference in body weight was observed whatever the administered molecules. Conclusion: Administration of ALF-5775 improves blood glucose and insulin sensitivity in insulin-resistant mice. This effect is mediated by an increase of skeletal muscle glucose uptake through AMPK activation. REG3A is a potential therapeutic drug for the management of insulin resistance syndrome. Disclosure M. Darnaud: None. C. Cruciani-Guglielmacci: Consultant; Self; The Healthy Aging Company. P. Gonzalez: None. P. Amouyal: None. G. Amouyal: None. L. Jamot: None. N. Moniaux: None. F. Andreelli: Consultant; Self; Lilly Diabetes, THAC. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; Lilly Diabetes. C.B. Bréchot: Consultant; Self; Romark. Employee; Self; The Healthy Aging Company. C. Magnan: None. J. Faivre: None.

Published
2020

40. COVID-19-associated collapsing glomerulopathy: a report of two cases and literature review

Author

Alexis Mathian, Micheline Pha, Shadia Varnous, Nadia Arzouk, Ophelie Le Monnier, Philippe Couvert, Fabrizio Andreelli, Zahir Amoura, Danielle Seilhean, Philippe Cluzel, Hassan Izzedine, and Isabelle Brocheriou

Subjects
Adult, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Pathological, Acute tubular necrosis, Dialysis, Coronavirus, business.industry, Acute kidney injury, COVID-19, Acute Kidney Injury, Middle Aged, medicine.disease, Female, Kidney Cortex Necrosis, business, Nephrotic syndrome
Abstract

Nephrotic range proteinuria has been reported during the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). However, the pathological mechanisms underlying this manifestation are unknown. In this article, we present two cases of collapsing glomerulopathy (CG) associated with acute tubular necrosis during the course of COVID-19, and review the literature for similar reports. In our two cases, as in the 14 cases reported so far, the patients were of African ancestry. The 14 patients assessed had an APOL1 high-risk genotype. At the end of the reported period, two patients had died and five patients were still requiring dialysis. The 16 cases detailed in the present report strongly argue in favour of a causal link between SARS-CoV-2 infection and the occurrence of CG in patients homozygous for APOL1 high-risk genotype for which the term COVID-associated nephropathy (COVIDAN) can be put forward.

Published
2020

41. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Hugo Roume, Gwen Falony, Jean-Daniel Zucker, Sothea Touch, Lars Køber, Sofia K. Forslund, Fabrizio Andreelli, Stanislav Dusko Ehrlich, Luis Pedro Coelho, Peer Bork, Jens Nielsen, Karen E. Assmann, Marc-Emmanuel Dumas, Thi Thuy Duyen Nguyen, Christine Rouault, Sara Vieira-Silva, Helle Krogh Pedersen, Torben Hansen, Eugeni Belda, Sebastian Proost, Nathalie Galleron, Mireia Valles-Colomer, Christian Lewinter, Trine Nielsen, Jens Peter Gøtze, Michael Stumvoll, Pilar Galan, Jean-Michel Oppert, Judith Aron-Wisnewsky, Jean-Sébastien Hulot, Ivica Letunic, Nadja B Søndertoft, Benoit Quinquis, Joe-Elie Salem, Karine Clément, Tue H. Hansen, Rima Chakaroun, Fredrik Bäckhed, Nicolas Pons, Jens J. Holst, Henrik Vestergaard, Edi Prifti, Jean-Phillippe Bastard, Jeroen Raes, Oluf Pedersen, Valentina Tremaroli, Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Dept Biol Struct, Flanders Institute for Biotechnology, Integromics [Paris], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Medical Department III – Endocrinology, Nephrology, Rheumatology, Universität Leipzig [Leipzig], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Université Catholique de Louvain (UCL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), VIB-KU Leuven Center for Microbiology [Leuven, Belgium], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), University of Gothenburg (GU), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Tenon [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fudan University [Shanghai], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Metabolism, Digestion and Reproduction, Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biobyte Solution, Department of Biology and Biological Engineering, Chalmers University of Technology, Chalmers University of Technology [Gothenburg, Sweden], European Molecular Biology Laboratory (EMBL), University of Heidelberg, Medical Faculty, University of Würzburg, Wallenberg Laboratory, Göteborgs Universitet (GU), The promotor of the clinical study was the Assistance Publique Hôpitaux de Paris (APHP). S.V.-S. was supported by a post-doctoral fellowship from the Research Foundation Flanders (FWO Vlaanderen). The Raes laboratory is supported by the VIB Grand Challenges programme, KU Leuven, the Rega Institute for Medical Research, and the FWO EOS program (30770923). The Novo Nordisk Foundation Center for Basic Metabolic Research., ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], LE CHATELIER, Emmanuelle, Démonstrateurs - MetaGenoPolis - - MGP2011 - ANR-11-DPBS-0001 - DPBS - VALID, Instituts Hospitalo-Universitaires - Institut de Cardiologie-Métabolisme-Nutrition - - ICAN2010 - ANR-10-IAHU-0005 - IAHU - VALID, Metagenomics in Cardiometabolic Diseases - METACARDIS - - EC:FP7:HEALTH2012-11-01 - 2017-10-31 - 305312 - VALID, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), VIB-KU Leuven Center for Microbiology [Belgium], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Service de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC Paris Est, Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
0301 basic medicine, Male, Feces/microbiology, [SDV]Life Sciences [q-bio], Overweight, Gut flora, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Cohort Studies, Feces, 0302 clinical medicine, Prevalence, Medicine, Bacteroides, Gastrointestinal Microbiome/drug effects, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, education.field_of_study, Multidisciplinary, biology, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Enterotype, Female, medicine.symptom, Inflammatory Bowel Diseases/microbiology, Obesity/microbiology, medicine.medical_specialty, Bacteroides/isolation & purification, Population, 03 medical and health sciences, Internal medicine, Humans, Microbiome, Obesity, education, Faecalibacterium, business.industry, medicine.disease, biology.organism_classification, Inflammatory Bowel Diseases, Gastrointestinal Microbiome, MetaCardis Consortium, Dysbiosis/epidemiology, 030104 developmental biology, Cross-Sectional Studies, Dysbiosis, Faecalibacterium/isolation & purification, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Body mass index
Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.

Published
2020

42. Effets cardio-métaboliques des glucides

Author

C. Amouyal, Héléna Mosbah, and Fabrizio Andreelli

Subjects
03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine
Abstract

Resume Les evenements cardiovasculaires restent une cause importante de mortalite prematuree. Des travaux epidemiologiques et experimentaux chez l’homme et l’animal suggerent que les sucres ajoutes, dont le fructose et le saccharose, peuvent majorer la pression arterielle, la frequence cardiaque, le risque d’arythmie cardiaque, l’insulinoresistance, la steatose hepatique, tout en favorisant l’inflexibilite metabolique cardiaque. Il serait important que les societes savantes se penchent sur la question des sucres ajoutes, d’autant que ceux-ci sont souvent associes a du sel en exces, dont le cumul pourrait augmenter le risque cardiovasculaire.

Published
2018

43. Vers de nouvelles recommandations pour la chirurgie du diabète de type 2 ?

Author

Fabrizio Andreelli and Patrick Ritz

Subjects
03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030209 endocrinology & metabolism, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine
Abstract

Resume La chirurgie bariatrique est reconnue comme un traitement efficace, non seulement de l’obesite, mais aussi du diabete de type 2 (DT2). Des meta-analyses recentes montrent que la disparition du DT2 en post-operatoire, toutes techniques chirurgicales confondues, atteint 78 %, ce qui est un resultat remarquable. Cet effet benefique est d’autant plus frequemment observe que le type de chirurgie associe restriction et malabsorption, comme le bypass gastrique selon la technique du Roux-en-Y. Ces resultats benefiques observes dans des populations obeses dont l’indice de masse corporelle (IMC) est superieur a 35 kg/m2 ont conduit a l’emergence du concept de traitement chirurgical du DT2. Comme les effets metaboliques benefiques postoperatoires ne sont pas completement dependants de la perte ponderale, le terme « chirurgie metabolique » semble plus approprie que le terme chirurgie bariatrique lorsque l’on considere les changements de glycemie induits par la chirurgie. La chirurgie metabolique pour des populations atteintes de DT2 et dont l’IMC est

Published
2018

44. Insuffisance cardiaque et diabète

Author

Fabrizio Andreelli

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published
2021

46. Variability in clinical presentation of diabetes mellitus during anti-PD-1 immunotherapy

Author

A Boudifa, Agnès Hartemann, Marie Bastin, Aurélie Carlier, Fabrizio Andreelli, A. Villemain, and Héléna Mosbah

Subjects
Oncology, medicine.medical_specialty, biology, Diabetic ketoacidosis, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Anti pd 1, General Medicine, Immunotherapy, medicine.disease, Endocrinology, Programmed cell death 1, Internal medicine, Diabetes mellitus, Internal Medicine, biology.protein, medicine, Presentation (obstetrics), Nivolumab, business
Published
2020

47. Insulin Pump Combined with Flash Glucose Monitoring: A Therapeutic Option to Improve Glycemic Control in Severely Nonadherent Patients with Type 1 Diabetes

Author

Marc Popelier, Olivier Bourron, Sophie Jacqueminet, Stephanie Rouanet, Cécile Ciangura, Frederic Bosquet, Chloé Amouyal, Fabrizio Andreelli, M. Halbron, and Agnès Hartemann

Subjects
Insulin pump, Adult, Male, medicine.medical_specialty, endocrine system diseases, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Pilot Projects, 03 medical and health sciences, Flash (photography), Young Adult, 0302 clinical medicine, Endocrinology, Insulin Infusion Systems, Treatment compliance, Internal medicine, Diabetes mellitus, Medicine, Humans, Hypoglycemic Agents, Insulin, 030212 general & internal medicine, Prospective Studies, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, Blood Glucose Self-Monitoring, nutritional and metabolic diseases, medicine.disease, Intention to Treat Analysis, Medical Laboratory Technology, Diabetes Mellitus, Type 1, Treatment Outcome, Patient Compliance, Female, business
Abstract

Some patients with type 1 diabetes (T1D) are severely noncompliant; they rarely perform self-blood glucose measures and miss insulin injections. Their HbA1c is far above the target rate. Current guidelines do not recommend starting treatment with an insulin pump (continuous subcutaneous insulin infusion [CSII]) for these persons. The aim of this study was to determine whether a CSII associated with a flash glucose monitoring (FGM) device could reduce HbA1c without increasing the risk of acute events, diabetic ketoacidosis (DKA) and severe hypoglycemia (SH), in these patients. We conducted a 6-month nonrandomized, pilot prospective study. Patients with T1D on multiple daily injections who performed less than two self-blood glucose tests/day and had an HbA1c9% were equipped with CSII and an FGM device. The primary composite endpoint was defined by a change in HbA1c ≥1% without any episode of DKA or SH during 6 months. Change in mean HbA1c, weight, treatment satisfaction, frequency of minor hypoglycemia, and ketoacidosis were secondary endpoints. Nineteen adults were included. Median (Q

Published
2019

48. Diabetes Mellitus, Extreme Insulin Resistance, and Hypothalamic-Pituitary Langerhans Cells Histiocytosis

Author

Corinne Vigouroux, Marie Bastin, Mathilde Sollier, Fabrizio Andreelli, Ahmed Idbaih, Jean Donadieu, Agnès Hartemann, Fleur Cohen Aubart, Chloé Amouyal, Philippe Touraine, Martine Auclair, M. Halbron, Olivier Bourron, G. Bera, Jacques Young, and Héléna Mosbah

Subjects
Pathology, medicine.medical_specialty, Langerin, Endocrinology, Diabetes and Metabolism, Case Report, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, Diabetes mellitus, Biopsy, medicine, 030212 general & internal medicine, Cladribine, Histiocyte, lcsh:RC648-665, biology, medicine.diagnostic_test, business.industry, medicine.disease, Histiocytosis, 030220 oncology & carcinogenesis, Diabetes insipidus, biology.protein, business, medicine.drug
Abstract

Background. Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm characterized by an infiltration of organs by Langerin + (CD207+) and CD1a+ histiocytes. Diabetes insipidus is a frequent manifestation of the disease, while diabetes mellitus is very rare. We report the first case of a 20-year-old man suffering from hypothalamopituitary histiocytosis and diabetes mellitus with serum anti-insulin receptor antibodies. Case Presentation. A 20-year-old patient was admitted for the evaluation of growth delay and hyperphagia. HbA1c level and fasting blood glucose were in the normal range. The diagnosis of hypothalamopituitary histiocytosis was based on histological features after biopsy of a large suprachiasmatic lesion identified on magnetic resonance imaging (MRI). Association of vinblastine and purinethol was started followed by a second-line therapy by cladribine. During the follow-up, the patient was admitted for recurrence of hyperglycemic states and extreme insulin resistance. The screening for serum anti-insulin receptor antibodies was positive. Each episode of hyperglycemia appeared to be correlated with tumoral activity and increase in serum anti-insulin receptor antibodies and appeared to be improved when the disease was controlled by chemotherapy. Conclusion. We report the first description of a hypothalamopituitary histiocytosis associated with serum anti-insulin receptor antibodies, extreme insulin resistance, and diabetes. Parallel evolution of glucose levels and serum anti-insulin receptor antibodies seemed to be the consequence of immune suppressive properties of cladribine.

Published
2019

49. Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in people with type 2 diabetes and chronic kidney disease. The French Chronic Kidney Disease – Renal Epidemiology and Information Network (CKD-REIN) Study

Author

L. Frimat, Christian Jacquelinet, Serge Briançon, Denis Fouque, Elodie Speyer, Fabrizio Andreelli, R. Pisoni, Carole Ayav, Ziad A. Massy, Bénédicte Stengel, Maurice Laville, Beverley Balkau, Marie Metzger, Christian Combe, University of Versailles St.-Quentin, UMRS 1018, Villejuif, Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Arbor Research Collaborative for Health, CKD REIN, Service de diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and CCSD, Accord Elsevier

Subjects
Male, medicine.medical_specialty, Databases, Factual, Epidemiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Chronic kidney disease, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Diabetic Nephropathies, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Aged, Information Services, business.industry, Insulin, General Medicine, medicine.disease, 3. Good health, Metformin, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Albuminuria, Drug Therapy, Combination, Female, Sex, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, Glucose lowering treatments, business, Hypoglycaemia, medicine.drug, Kidney disease
Abstract

Aim To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. Methods Among the 3033 patients with CKD stages 3–5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. Results Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54 mmol/mol) in men, 7.4% (57 mmol/mol) in women (P = 0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. Conclusion Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women.

Published
2019

50. Pregnant type 1 diabetes women with rises in C-peptide display higher levels of regulatory T cells: A pilot study

Author

Michelle Rosenzwajg, Agnès Hartemann, Joe-Elie Salem, M. Popelier, M. Halbron, C. Ciangura, Fabrizio Andreelli, David Klatzmann, Olivier Bourron, S. Jacqueminet, E. Tibi, Chloé Amouyal, and Rosenzwajg, Michelle

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Pregnancy in Diabetics, Pilot Projects, chemical and pharmacologic phenomena, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, T-Lymphocytes, Regulatory, Flow cytometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Pregnancy, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Interleukine 2, Type 1 diabetes, C-Peptide, medicine.diagnostic_test, C-peptide, business.industry, Insulin, hemic and immune systems, Regulatory T cells, General Medicine, medicine.disease, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 1, Cytokine, chemistry, Cohort, Interleukin-2, Female, business, C peptide
Abstract

Aim During pregnancy of type 1 diabetes (T1D) women, a C peptide rise has been described, which mechanism is unclear. In T1D, a defect of regulatory T cells (Tregs) and its major controlling cytokine, interleukin-2 (IL2), is observed. Methods Evolution of clinical, immunological (Treg (CD4+CD25hiCD127-/loFoxp3+ measured by flow cytometry and IL2 measured by luminex xMAP technology) and diabetes parameters (insulin dose per day, HbA1C, glycaemia, C peptide) was evaluated in 13 T1D women during the three trimesters of pregnancy and post-partum (PP, within 6 months) in a monocentric pilot study. Immunological parameters were compared with those of a healthy pregnant cohort (QuTe). Results An improvement of beta cell function (C peptide rise and/or a decrease of insulin dose-adjusted A1c index that estimate individual exogenous insulin need) was observed in seven women (group 1) whereas the six others (group 2) did not display any positive response to pregnancy. A higher level of Tregs and IL2 was observed in group 1 compared to group 2 during pregnancy and at PP for Tregs level. However, compared to the healthy cohort, T1D women displayed a Treg deficiency Conclusion This pilot study highlights that higher level of Tregs and IL2 seem to allow improvement of endogenous insulin secretion of T1D women during pregnancy.

Published
2021

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