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1. GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise

Author

Axel Labour, Marlène Lac, Lucas Frassin, Benjamin Lair, Enda Murphy, Claire Maslo, Laurent Monbrun, Marie-Lou Calmy, Marie Marquès, Nathalie Viguerie, Geneviève Tavernier, Pierre Gourdy, Donal O’Gorman, Emilie Montastier, Claire Laurens, Alexandra Montagner, and Cedric Moro

Subjects
CP: Metabolism, Biology (General), QH301-705.5
Abstract

Summary: Growth and differentiation factor 15 (GDF15) has recently emerged as a weight loss and insulin-sensitizing factor. Growing evidence also supports a role for GDF15 as a physiological, exercise-induced stress signal. Here, we tested whether GDF15 is required for the insulin-sensitizing effects of exercise in mice and humans. At baseline, both under a standard nutritional state and high-fat feeding, GDF15 knockout (KO) mice display normal glucose tolerance, systemic insulin sensitivity, maximal speed, and endurance running capacity when compared to wild-type littermates independent of sex. When submitted to a 4-week exercise training program, both lean and obese wild-type and GDF15 KO mice similarly improve their endurance running capacity, glucose tolerance, systemic insulin sensitivity, and peripheral glucose uptake. Insulin-sensitizing effects of exercise training were also unrelated to changes in plasma GDF15 in humans. In summary, we here show that GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise.

Published
2024
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2. The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis

Author

Marc Schoeler, Sandrine Ellero-Simatos, Till Birkner, Jordi Mayneris-Perxachs, Lisa Olsson, Harald Brolin, Ulrike Loeber, Jamie D. Kraft, Arnaud Polizzi, Marian Martí-Navas, Josep Puig, Antonio Moschetta, Alexandra Montagner, Pierre Gourdy, Christophe Heymes, Hervé Guillou, Valentina Tremaroli, José Manuel Fernández-Real, Sofia K. Forslund, Remy Burcelin, and Robert Caesar

Subjects
Science
Abstract

Abstract Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.

Published
2023
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3. Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM)

Author

Pierre Gourdy, Patrice Darmon, François Dievart, Jean-Michel Halimi, and Bruno Guerci

Subjects
Glucagon-like peptide-1 receptor agonists, Sodium-glucose cotransporter-2 inhibitors, Type 2 diabetes mellitus, Combination therapy, Cardiovascular protection, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age ≥ 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities.

Published
2023
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4. Atherosclerotic cardiovascular disease risk stratification and management in type 2 diabetes: review of recent evidence-based guidelines

Author

Pierre Gourdy, François Schiele, Jean-Michel Halimi, Serge Kownator, Samy Hadjadj, and Paul Valensi

Subjects
atherosclerotic cardiovascular disease, type 2 diabetes, risk assessment, risk stratification, guidelines, prevention, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD. Thus, the purpose of this paper is to discuss recent evidence-based guidelines on ASCVD risk stratification and prevention in patients with T2DM, in terms of disparities and similarities. To close the gap between different guidelines, a multidisciplinary approach involving general practitioners, endocrinologists, and cardiologists may enhance the coordination of diagnosis, therapy, and long-term follow-up of ASCVD in patients with T2DM.

Published
2023
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5. The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

Author

Gemma Llauradó, Bogdan Vlacho, Matthieu Wargny, Yue Ruan, Josep Franch-Nadal, Pere Domingo, Pierre Gourdy, Pierre-Jean Saulnier, Samy Hadjadj, Sarah H. Wild, Rustam Rea, Bertrand Cariou, Kamlesh Khunti, Dídac Mauricio, and for the CORONADO, the ABCD COVID-19 diabetes national audit, HM Hospitales investigators and the Hospital del Mar - Hospital de la Santa Creu i Sant Pau Diabetes Research Group

Subjects
Diabetes, Macrovascular disease, Mortality, COVID-19, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.

Published
2022
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6. Membrane estrogen receptor-α contributes to female protection against high-fat diet-induced metabolic disorders

Author

Aurélie Fabre, Blandine Tramunt, Alexandra Montagner, Céline Mouly, Elodie Riant, Marie-Lou Calmy, Marine Adlanmerini, Coralie Fontaine, Rémy Burcelin, Françoise Lenfant, Jean-François Arnal, and Pierre Gourdy

Subjects
sex differences, estrogen receptor alpha (ERα), membrane-initiated steroid signaling, obesity, insulin resistance, thermogenesis, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

BackgroundEstrogen Receptor α (ERα) is a significant modulator of energy balance and lipid/glucose metabolisms. Beyond the classical nuclear actions of the receptor, rapid activation of intracellular signaling pathways is mediated by a sub-fraction of ERα localized to the plasma membrane, known as Membrane Initiated Steroid Signaling (MISS). However, whether membrane ERα is involved in the protective metabolic actions of endogenous estrogens in conditions of nutritional challenge, and thus contributes to sex differences in the susceptibility to metabolic diseases, remains to be clarified.MethodsMale and female C451A-ERα mice, harboring a point mutation which results in the abolition of membrane localization and MISS-related effects of the receptor, and their wild-type littermates (WT-ERα) were maintained on a normal chow diet (NCD) or fed a high-fat diet (HFD). Body weight gain, body composition and glucose tolerance were monitored. Insulin sensitivity and energy balance regulation were further investigated in HFD-fed female mice.ResultsC451A-ERα genotype had no influence on body weight gain, adipose tissue accumulation and glucose tolerance in NCD-fed mice of both sexes followed up to 7 months of age, nor male mice fed a HFD for 12 weeks. In contrast, compared to WT-ERα littermates, HFD-fed C451A-ERα female mice exhibited: 1) accelerated fat mass accumulation, liver steatosis and impaired glucose tolerance; 2) whole-body insulin resistance, assessed by hyperinsulinemic-euglycemic clamps, and altered insulin-induced signaling in skeletal muscle and liver; 3) significant decrease in energy expenditure associated with histological and functional abnormalities of brown adipose tissue and a defect in thermogenesis regulation in response to cold exposure.ConclusionBesides the well-characterized role of ERα nuclear actions, membrane-initiated ERα extra-nuclear signaling contributes to female, but not to male, protection against HFD-induced obesity and associated metabolic disorders in mouse.

Published
2023
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7. Selective Liver Estrogen Receptor α Modulation Prevents Steatosis, Diabetes, and Obesity Through the Anorectic Growth Differentiation Factor 15 Hepatokine in Mice

Author

Maeva Guillaume, Elodie Riant, Aurélie Fabre, Isabelle Raymond‐Letron, Melissa Buscato, Morgane Davezac, Blandine Tramunt, Alexandra Montagner, Sarra Smati, Rana Zahreddine, Gaëlle Palierne, Marie‐Cécile Valera, Hervé Guillou, Françoise Lenfant, Klaus Unsicker, Raphaël Metivier, Coralie Fontaine, Jean‐François Arnal, and Pierre Gourdy

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Hepatocyte estrogen receptor α (ERα) was recently recognized as a relevant molecular target for nonalcoholic fatty liver disease (NAFLD) prevention. The present study defined to what extent hepatocyte ERα could be involved in preserving metabolic homeostasis in response to a full (17β‐estradiol [E2]) or selective (selective estrogen receptor modulator [SERM]) activation. Ovariectomized mice harboring a hepatocyte‐specific ERα deletion (LERKO mice) and their wild‐type (WT) littermates were fed a high‐fat diet (HFD) and concomitantly treated with E2, tamoxifen (TAM; the most used SERM), or vehicle. As expected, both E2 and TAM prevented all HFD‐induced metabolic disorders in WT mice, and their protective effects against steatosis were abolished in LERKO mice. However, while E2 still prevented obesity and glucose intolerance in LERKO mice, hepatocyte ERα deletion also abrogated TAM‐mediated control of food intake as well as its beneficial actions on adiposity, insulin sensitivity, and glucose homeostasis, suggesting a whole‐body protective role for liver‐derived circulating factors. Moreover, unlike E2, TAM induced a rise in plasma concentration of the anorectic hepatokine growth differentiation factor 15 (Gdf15) through a transcriptional mechanism dependent on hepatocyte ERα activation. Accordingly, ERα was associated with specific binding sites in the Gdf15 regulatory region in hepatocytes from TAM‐treated mice but not under E2 treatment due to specific epigenetic modifications. Finally, all the protective effects of TAM were abolished in HFD‐fed GDF15‐knockout mice. Conclusion: We identified the selective modulation of hepatocyte ERα as a pharmacologic strategy to induce sufficient anorectic hepatokine Gdf15 to prevent experimental obesity, type 2 diabetes, and NAFLD.

Published
2019
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8. 17β-estradiol promotes acute refeeding in hungry mice via membrane-initiated ERα signaling

Author

Kaifan Yu, Yanlin He, Ilirjana Hyseni, Zhou Pei, Yongjie Yang, Pingwen Xu, Xing Cai, Hesong Liu, Na Qu, Hailan Liu, Yang He, Meng Yu, Chen Liang, Tingting Yang, Julia Wang, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Yong Xu, and Chunmei Wang

Subjects
E2, Feeding, ERα, Hypothalamus, Glucose-sensing, Internal medicine, RC31-1245
Abstract

Objective: Estrogen protects animals from obesity through estrogen receptor α (ERα), partially by inhibiting overeating in animals fed ad libitum. However, the effects of estrogen on feeding behavior in hungry animals remain unclear. In this study, we examined the roles of 17β-estradiol (E2) and ERα in the regulation of feeding in hungry female animals and explored the underlying mechanisms. Methods: Wild-type female mice with surgical depletion of endogenous estrogens were used to examine the effects of E2 supplementation on acute refeeding behavior after starvation. ERα-C451A mutant mice deficient in membrane-bound ERα activity and ERα-AF20 mutant mice lacking ERα transcriptional activity were used to further examine mechanisms underlying acute feeding triggered by either fasting or central glucopenia (induced by intracerebroventricular injections of 2-deoxy-D-glucose). We also used electrophysiology to explore the impact of these ERα mutations on the neural activities of ERα neurons in the hypothalamus. Results: In the wild-type female mice, ovariectomy reduced fasting-induced refeeding, which was restored by E2 supplementation. The ERα-C451A mutation, but not the ERα-AF20 mutation, attenuated acute feeding induced by either fasting or central glucopenia. The ERα-C451A mutation consistently impaired the neural responses of hypothalamic ERα neurons to hypoglycemia. Conclusion: In addition to previous evidence that estrogen reduces deviations in energy balance by inhibiting eating at a satiated state, our findings demonstrate the unexpected role of E2 that promotes eating in hungry mice, also contributing to the stability of energy homeostasis. This latter effect specifically requires membrane-bound ERα activity.

Published
2020
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9. Estrogen receptor subcellular localization and cardiometabolism

Author

Pierre Gourdy, Maeva Guillaume, Coralie Fontaine, Marine Adlanmerini, Alexandra Montagner, Henrik Laurell, Françoise Lenfant, and Jean-François Arnal

Subjects
Internal medicine, RC31-1245
Abstract

Background: In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular tissues. As a member of the nuclear receptor superfamily, ERα was primarily considered as a transcription factor that controls gene expression through the activation of its two activation functions (ERαAF-1 and ERαAF-2). However, besides these nuclear actions, a pool of ERα is localized in the vicinity of the plasma membrane, where it mediates rapid signaling effects called membrane-initiated steroid signals (MISS) that have been well described in vitro, especially in endothelial cells. Scope of the review: This review aims to summarize our current knowledge of the mechanisms of nuclear vs membrane ERα activation that contribute to the cardiometabolic protection conferred by estrogens. Indeed, new transgenic mouse models (affecting either DNA binding, activation functions or membrane localization), together with the use of novel pharmacological tools that electively activate membrane ERα effects recently allowed to begin to unravel the different modes of ERα signaling in vivo. Conclusion: Altogether, available data demonstrate the prominent role of ERα nuclear effects, and, more specifically, of ERαAF-2, in the preventive effects of estrogens against obesity, diabetes, and atheroma. However, membrane ERα signaling selectively mediates some of the estrogen endothelial/vascular effects (NO release, reendothelialization) and could also contribute to the regulation of energy balance, insulin sensitivity, and glucose metabolism. Such a dissection of ERα biological functions related to its subcellular localization will help to understand the mechanism of action of “old” ER modulators and to design new ones with an optimized benefit/risk profile. Keywords: Estrogen receptors, Genomic effects, Membrane-initiated steroid signals, Energy balance, Glucose homeostasis, Cardiovascular system

Published
2018
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10. Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

Author

Blandine Tramunt, Alexandra Montagner, Nguan Soon Tan, Pierre Gourdy, Hervé Rémignon, and Walter Wahli

Subjects
estrogen receptors, G protein-coupled estrogen receptor, nuclear receptors, vitellogenin, sexual dimorphism, liver diseases, Microbiology, QR1-502
Abstract

The liver is a vital organ that sustains multiple functions beneficial for the whole organism. It is sexually dimorphic, presenting sex-biased gene expression with implications for the phenotypic differences between males and females. Estrogens are involved in this sex dimorphism and their actions in the liver of several reptiles, fishes, amphibians, and birds are discussed. The liver participates in reproduction by producing vitellogenins (yolk proteins) and eggshell proteins under the control of estrogens that act via two types of receptors active either mainly in the cell nucleus (ESR) or the cell membrane (GPER1). Estrogens also control hepatic lipid and lipoprotein metabolisms, with a triglyceride carrier role for VLDL from the liver to the ovaries during oogenesis. Moreover, the activation of the vitellogenin genes is used as a robust biomarker for exposure to xenoestrogens. In the context of liver diseases, high plasma estrogen levels are observed in fatty liver hemorrhagic syndrome (FLHS) in chicken implicating estrogens in the disease progression. Fishes are also used to investigate liver diseases, including models generated by mutation and transgenesis. In conclusion, studies on the roles of estrogens in the non-mammalian oviparous vertebrate liver have contributed enormously to unveil hormone-dependent physiological and physiopathological processes.

Published
2021
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11. Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

Author

F. Balazard, S. Le Fur, S. Valtat, A. J. Valleron, P. Bougnères, Isis-Diab collaborative group, Dominique Thevenieau, Corinne Fourmy Chatel, Rachel Desailloud, Hélène Bony-Trifunovic, Pierre-Henri Ducluzeau, Régis Coutant, Sophie Caudrelier, Armelle Pambou, Emmanuelle Dubosclard, Florence Joubert, Philippe Jan, Estelle Marcoux, Anne-Marie Bertrand, Brigitte Mignot, Alfred Penformis, Chantal Stuckens, Régis Piquemal, Pascal Barat, Vincent Rigalleau, Chantal Stheneur, Sylviane Fournier, Véronique Kerlan, Chantal Metz, Anne Fargeot-Espaliat, Yves Reznic, Frédérique Olivier, Iva Gueorguieva, Arnaud Monier, Catherine Radet, Vincent Gajdos, Daniel Terral, Christine Vervel, Djamel Bendifallah, Candace Ben Signor, Daniel Dervaux, Abdelkader Benmahammed, Guy-André Loeuille, Françoise Popelard, Agnès Guillou, Pierre-Yves Benhamou, Jamil Khoury, Jean-Pierre Brossier, Joachim Bassil, Sylvaine Clavel, Bernard Le Luyer, Pierre Bougnères, Françoise Labay, Isabelle Guemas, Jacques Weill, Jean-Pierre Cappoen, Sylvie Nadalon, Anne Lienhardt-Roussie, Anne Paoli, Claudie Kerouedan, Edwige Yollin, Marc Nicolino, Gilbert Simonin, Jacques Cohen, Catherine Atlan, Agnès Tamboura, Hervé Dubourg, Marie-Laure Pignol, Philippe Talon, Stéphanie Jellimann, Lucy Chaillous, Sabine Baron, Marie-Noëlle Bortoluzzi, Elisabeth Baechler, Randa Salet, Ariane Zelinsky-Gurung, Fabienne Dallavale, Etienne Larger, Marie Laloi-Michelin, Jean-François Gautier, Bénédicte Guérin, Laure Oilleau, Laetitia Pantalone, Céline Lukas, Isabelle Guilhem, Marc De Kerdanet, Marie-Claire Wielickzo, Mélanie Priou-Guesdon, Odile Richard, François Kurtz, Norbert Laisney, Déborah Ancelle, Guilhem Parlier, Catherine Boniface, Dominique Paris Bockel, Denis Dufillot, Berthe Razafimahefa, Pierre Gourdy, Pierre Lecomte, Myriam Pepin-Donat, Marie-Emmanuelle Combes-Moukhovsky, Brigitte Zymmermann, Marina Raoulx, and Anne Gourdin et Catherine Dumont

Subjects
Case–control, Epidemiology, Type 1 diabetes, Data-driven, Environment, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. Methods Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. Results We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. Conclusions The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. Trial registration Clinical-Trial.gov NCT02212522 . Registered August 6, 2014.

Published
2016
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12. Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety

Author

Emmanuel Guivarc'h, Mélissa Buscato, Anne‐Laure Guihot, Julie Favre, Emilie Vessières, Linda Grimaud, Jamal Wakim, Nada‐Joe Melhem, Rana Zahreddine, Marine Adlanmerini, Laurent Loufrani, Claude Knauf, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Jean‐Michel Foidart, Pierre Gourdy, Françoise Lenfant, Jean‐François Arnal, Daniel Henrion, and Coralie Fontaine

Subjects
arteriolar remodeling, atherosclerosis, estrogen, hypertension, nuclear receptor, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Although estrogen receptor α (ERα) acts primarily as a transcription factor, it can also elicit membrane‐initiated steroid signaling. Pharmacological tools and transgenic mouse models previously highlighted the key role of ERα membrane‐initiated steroid signaling in 2 actions of estrogens in the endothelium: increase in NO production and acceleration of reendothelialization. Methods and Results Using mice with ERα mutated at cysteine 451 (ERaC451A), recognized as the key palmitoylation site required for ERα plasma membrane location, and mice with disruption of nuclear actions because of inactivation of activation function 2 (ERaAF20 = ERaAF2°), we sought to fully characterize the respective roles of nuclear versus membrane‐initiated steroid signaling in the arterial protection conferred by ERα. ERaC451A mice were fully responsive to estrogens to prevent atheroma and angiotensin II–induced hypertension as well as to allow flow‐mediated arteriolar remodeling. By contrast, ERαAF20 mice were unresponsive to estrogens for these beneficial vascular effects. Accordingly, selective activation of nuclear ERα with estetrol was able to prevent hypertension and to restore flow‐mediated arteriolar remodeling. Conclusions Altogether, these results reveal an unexpected prominent role of nuclear ERα in the vasculoprotective action of estrogens with major implications in medicine, particularly for selective nuclear ERα agonist, such as estetrol, which is currently under development as a new oral contraceptive and for hormone replacement therapy in menopausal women.

Published
2018
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13. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation

Author

Anne Abot, Coralie Fontaine, Mélissa Buscato, Romain Solinhac, Gilles Flouriot, Aurélie Fabre, Anne Drougard, Shyamala Rajan, Muriel Laine, Alain Milon, Isabelle Muller, Daniel Henrion, Marine Adlanmerini, Marie‐Cécile Valéra, Anne Gompel, Céline Gerard, Christel Péqueux, Mélanie Mestdagt, Isabelle Raymond‐Letron, Claude Knauf, François Ferriere, Philippe Valet, Pierre Gourdy, Benita S Katzenellenbogen, John A Katzenellenbogen, Françoise Lenfant, Geoffrey L Greene, Jean‐Michel Foidart, and Jean‐François Arnal

Subjects
endothelium, estetrol, estrogen receptor, uterus, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Estetrol (E4) is a natural estrogen with a long half‐life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand‐binding domain bound to 17β‐estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF‐1 and AF‐2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane‐initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS‐dependent effects in endothelium but also in MCF‐7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.

Published
2014
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15. High-fat diet induces periodontitis in mice through lipopolysaccharides (LPS) receptor signaling: protective action of estrogens.

Author

Vincent Blasco-Baque, Matteo Serino, Jean-Noël Vergnes, Elodie Riant, Pascale Loubieres, Jean-François Arnal, Pierre Gourdy, Michel Sixou, Rémy Burcelin, and Philippe Kemoun

Subjects
Medicine, Science
Abstract

BackgroundA fat-enriched diet favors the development of gram negative bacteria in the intestine which is linked to the occurrence of type 2 diabetes (T2D). Interestingly, some pathogenic gram negative bacteria are commonly associated with the development of periodontitis which, like T2D, is characterized by a chronic low-grade inflammation. Moreover, estrogens have been shown to regulate glucose homeostasis via an LPS receptor dependent immune-modulation. In this study, we evaluated whether diet-induced metabolic disease would favor the development of periodontitis in mice. In addition, the regulatory role of estrogens in this process was assessed.MethodsFour-week-old C57BL6/J WT and CD14 (part of the TLR-4 machinery for LPS-recognition) knock-out female mice were ovariectomised and subcutaneously implanted with pellets releasing either placebo or 17β-estradiol (E2). Mice were then fed with either a normal chow or a high-fat diet for four weeks. The development of diabetes was monitored by an intraperitoneal glucose-tolerance test and plasma insulin concentration while periodontitis was assessed by identification of pathogens, quantification of periodontal soft tissue inflammation and alveolar bone loss.ResultsThe fat-enriched diet increased the prevalence of periodontal pathogenic microbiota like Fusobacterium nucleatum and Prevotella intermedia, gingival inflammation and alveolar bone loss. E2 treatment prevented this effect and CD14 knock-out mice resisted high-fat diet-induced periodontal defects.Conclusions/significanceOur data show that mice fed with a diabetogenic diet developed defects and microflora of tooth supporting-tissues typically associated with periodontitis. Moreover, our results suggest a causal link between the activation of the LPS pathway on innate immunity by periodontal microbiota and HFD-induced periodontitis, a pathophysiological mechanism that could be targeted by estrogens.

Published
2012
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16. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex

Author

Tae Won Yi, Brendan Smyth, Gian Luca Di Tanna, Clare Arnott, Kathryn Cardoza, Amy Kang, Carol Pollock, Rajiv Agarwal, George Bakris, David M. Charytan, Dick de Zeeuw, Hiddo J.L. Heerspink, Bruce Neal, David C. Wheeler, Christopher P. Cannon, Hong Zhang, Bernard Zinman, Vlado Perkovic, Adeera Levin, Kenneth W. Mahaffey, Meg Jardine, Barry M. Brenner, Tom Greene, Meg J. Jardine, Gary Meininger, Nicole Li, Inna Kolesnyk, Diego Aizenberg, Roberto Pecoits-Filho, David Cherney, Gregorio Obrador, Glenn Chertow, Tara Chang, Carmel Hawley, Linong Ji, Takashi Wada, Vivekanand Jha, Soo Kun Lim, Mary Anne Lim-Abrahan, Florence Santos, Dong-Wan Chae, Shang-Jyh Hwang, Evgueniy Vazelov, Ivan Rychlík, Samy Hadjadj, Vera Krane, László Rosivall, Luca De Nicola, Alexander Dreval, Michał Nowicki, Adalbert Schiller, Larry Distiller, Jose L. Górriz, Mykola Kolesnyk, null David, C. Wheeler, Rodolfo Andres Ahuad Guerrero, Juan Pablo Albisu, Andres Alvarisqueta, Ines Bartolacci, Mario Alberto Berli, Anselmo Bordonava, Pedro Calella, Maria Cecilia Cantero, Luis Rodolfo Cartasegna, Esteban Cercos, Gabriela Cecilia Coloma, Hugo Colombo, Victor Commendatore, Jesus Cuadrado, Carlos Alberto Cuneo, Ana Maria Cusumano, Walter Guillermo Douthat, Ricardo Dario Dran, Eduardo Farias, Maria Florencia Fernandez, Hernan Finkelstein, Guillermo Fragale, Jose Osvaldo Fretes, Nestor Horacio Garcia, Anibal Gastaldi, Elizabeth Gelersztein, Jorge Archibaldo Glenny, Joaquin Pablo Gonzalez, Patricia del Carmen Gonzalez Colaso, Claudia Goycoa, Gustavo Cristian Greloni, Adrian Guinsburg, Sonia Hermida, Luis Isaias Juncos, Maria Isabel Klyver, Florencia Kraft, Fernando Krynski, Paulina Virginia Lanchiotti, Ricardo Alfonso Leon de la Fuente, Nora Marchetta, Pablo Mele, Silvia Nicolai, Pablo Antonio Novoa, Silvia Ines Orio, Fabian Otreras, Alejandra Oviedo, Pablo Raffaele, Jorge Hector Resk, Lucas Rista, Nelson Rodriguez Papini, Jorgelina Sala, Juan Carlos Santos, Lilia Beatriz Schiavi, Horacio Sessa, Tomas Smith Casabella, Maria Rosa Ulla, Maria Valdez, Augusto Vallejos, Adriana Villarino, Virginia Esther Visco, Alfredo Wassermann, Cesar Javier Zaidman, Ngai Wah Cheung, Carolyn Droste, Ian Fraser, David Johnson, Peak Mann Mah, Kathy Nicholls, David Packham, Joseph Proietto, Anthony Roberts, Simon Roger, Venessa Tsang, Roberto Abrão Raduan, Fernando Augusto Alves da Costa, Celso Amodeo, Luiz Alberto Andreotti Turatti, Rachel Bregman, Fernanda Cristina Camelo Sanches, Luis Henrique Canani, Antônio Roberto Chacra, João Lindolfo Cunha Borges, Sérgio Alberto Cunha Vêncio, Roberto Jorge da Silva Franco, Domingos d’Avila, Evandro de Souza Portes, Pedro de Souza, Luciane Mônica Deboni, Fadlo Fraige Filho, Bruno Geloneze Neto, Marcus Gomes, Suely Keiko Kohara, Elizete Keitel, Jose Francisco Kerr Saraiva, Hugo Roberto Kurtz Lisboa, Fabiana Loss de Carvalho Contieri, Rosângela Milagres, Renan Montenegro Junior, Claudia Moreira de Brito, Miguel Nasser Hissa, Ângela Regina Nazario Sabbag, Irene Noronha, Daniel Panarotto, Roberto Pecoits Filho, Márcio Antônio Pereira, Wladmir Saporito, Antonio Scafuto Scotton, Tiago Schuch, Roberto Simões de Almeida, Cássio Slompo Ramos, João Soares Felício, Fernando Thomé, Jean Carlo Tibes Hachmann, Sérgio Yamada, Cesar Yoiti Hayashida, Tarissa Beatrice Zanata Petry, Maria Teresa Zanella, Viktoria Andreeva, Angelina Angelova, Stefan Dimitrov, Veselka Genadieva, Gabriela Genova-Hristova, Kiril Hristozov, Zdravko Kamenov, Atanas Koundurdjiev, Lachezar Lozanov, Viktor Margaritov, Boyan Nonchev, Rangel Rangelov, Alexander Shinkov, Margarita Temelkova, Ekaterina Velichkova, Andrian Yakov, Naresh Aggarwal, Ronnie Aronson, Harpreet Bajaj, Guy Chouinard, James Conway, Serge Cournoyer, Gerald DaRoza, Sacha De Serres, François Dubé, Ronald Goldenberg, Anil Gupta, Milan Gupta, Sam Henein, Hasnain Khandwala, Lawrence Leiter, François Madore, Alan McMahon, Norman Muirhead, Vincent Pichette, Remi Rabasa-Lhoret, Andrew Steele, Navdeep Tangri, Ali Torshizi, Vincent Woo, Nadia Zalunardo, María Alicia Fernández Montenegro, Juan Gonzalo Godoy Jorquera, Marcelo Medina Fariña, Victor Saavedra Gajardo, Margarita Vejar, Nan Chen, Qinkai Chen, Shenglian Gan, Yaozhong Kong, Detian Li, Wenge Li, Xuemei Li, Hongli Lin, Jian Liu, Weiping Lu, Hong Mao, Yan Ren, Weihong Song, Jiao Sun, Lin Sun, Ping Tu, Guixia Wang, Jinkui Yang, Aiping Yin, Xueqing Yu, Minghui Zhao, Hongguang Zheng, Jose Luis Accini Mendoza, Edgar Arcos, Jorge Avendano, Jorge Ernesto Andres Diaz Ruiz, Luis Hernando Garcia Ortiz, Alexander Gonzalez, Eric Hernandez Triana, Juan Diego Higuera, Natalia Malaver, Dora Inés Molina de Salazar, Ricardo Rosero, Monica Alexandra Terront Lozano, Luis Valderrama Cometa, Alex Valenzuela, Ruben Dario Vargas Alonso, Ivan Villegas, Hernan Yupanqui, Dagmar Bartaskova, Petr Barton, Jana Belobradkova, Lenka Dohnalova, Tomas Drasnar, Richard Ferkl, Katarina Halciakova, Vera Klokocnikova, Richard Kovar, Jiri Lastuvka, Martin Lukac, Satu Pesickova, Karel Peterka, Jiri Pumprla, Ivan Rychlik, Frantisek Saudek, Vladimir Tesar, Martin Valis, Pavel Weiner, Stanislav Zemek, Eric Alamartine, Sophie Borot, Bertrand Cariou, Bertrand Dussol, Jean-Pierre Fauvel, Pierre Gourdy, Alexandre Klein, Yannick Le Meur, Alfred Penfornis, Ronan Roussel, Pierre-Jean Saulnier, Eric Thervet, Philippe Zaoui, Volker Burst, Markus Faghih, Grit Faulmann, Hermann Haller, Reinhold Jerwan-Keim, Stephan Maxeiner, Björn Paschen, Georg Plassmann, Ludger Rose, Ronaldo Arturo Gonzalez Orellana, Franklin Paul Haase, Juan Pablo Moreira Diaz, Luis Alberto Ramirez Roca, Jose Antonio Sánchez Arenales, José Vicente Sanchez Polo, Erick Turcios Juarez, Gyongyi Csecsei, Botond Csiky, Peter Danos, Laszlo Deak, Mihaly Dudas, Eleonora Harcsa, Katalin Keltai, Sandor Keresztesi, Krisztian Kiss, Laszlo Konyves, Lajos Major, Margit Mileder, Marta Molnar, Janos Mucsi, Tamas Oroszlan, Ivan Ory, Gyorgy Paragh, Eva Peterfai, Gizella Petro, Katalin Revesz, Robert Takacs, Sandor Vangel, Szilard Vasas, Marianna Zsom, Oomman Abraham, Raju Sree Bhushan, Dewan Deepak, Fernando M. Edwin, Natarajan Gopalakrishnan, Noble Gracious, Alva Hansraj, Dinesh Jain, C.B. Keshavamurthy, Dinesh Khullar, Sahay Manisha, Jayameena Peringat, Narayan Prasad, Rao K. Satyanarayana, Reddy Sreedhar, Melemadathil Sreelatha, Bhimavarapu Sudhakar, Ramesh Chandra Vyasam, Riccardo Bonadonna, Pietro Castellino, Antonio Ceriello, Luca Chiovato, Salvatore De Cosmo, Giuseppe Derosa, Alberto Di Carlo, Graziano Di Cianni, Giovanni Frascà, Giorgio Fuiano, Giovanni Gambaro, Giacomo Garibotto, Carlo Giorda, Fabio Malberti, Marcora Mandreoli, Edoardo Mannucci, Emanuela Orsi, Piermarco Piatti, Domenico Santoro, Ferdinando Carlo Sasso, Gaetano Serviddio, Andrea Stella, Roberto Trevisan, Anna Maria Veronelli, Luca Zanoli, Hitoshi Akiyama, Hiromi Aoki, Akimichi Asano, Tadashi Iitsuka, Shizuo Kajiyama, Susumu Kashine, Toshio Kawada, Takamoto Kodera, Hiroshi Kono, Kazunori Koyama, Yasuro Kumeda, Shozo Miyauchi, Kazuyuki Mizuyama, Tetsuji Niiya, Hiroko Oishi, Satoshi Ota, Terue Sakakibara, Masahiko Takai, Osamu Tomonaga, Mitsuru Tsujimoto, Masakiyo Wakasugi, Yasushi Wakida, Takayuki Watanabe, Masayo Yamada, Kazuhiro Yanagida, Toshihiko Yanase, Wataru Yumita, Egle Gaupsiene, Dalia Kozloviene, Antanas Navickas, Egle Urbanaviciene, Rohana Abdul Ghani, Khalid Abdul Kadir, Norsiah Ali, Mohd Daud Che Yusof, Chye Lee Gan, Mastura Ismail, Wei Yen Kong, Swee Win Lam, Li Yuan Lee, Chek Loong Loh, Anita Bhajan Manocha, Kee Sing Ng, Nik Nur Fatnoon Nik Ahmad, Vanassa Ratnasingam, Saiful Shahrizal Bin Shudim, Paranthaman Vengadasalam, Luis David Abraira Munoz, Melchor Alpizar Salazar, Juan Baas Cruz, Mario Burgos Soto, Jose Chevaile Ramos, Alfredo Chew Wong, Jose Ricardo Correa Rotter, Tonatiu Diaz Escalante, Favio Edmundo Enriquez Sosa, Fernando Flores Lozano, Luis Fernando Flota Cervera, Paul Frenk Baron, Cecilia Garcia Ballesteros, Jose David Gomez Rangel, Luis Enrique Herrera Jimenez, Sergio Saul Irizar Santana, Fernando Jimenez Flores, Hugo Laviada Molina, Rosa Isela Luna Ceballos, Belia Martin del Campo Blanco, Guadalupe Morales Franco, Oscar Tarsicio Moreno Loza, Cynthia Mustieles Rocha, Gregorio Obrador Vera, Ricardo Orozco Castellanos, Juan Peralta Calcaneo, Miguel Angel Reyes Rosano, Hiromi Rodriguez Pattzi, Juan Rosas Guzman, Isabel Erika Rucker Joerg, Sandra Berenice Saavedra Sanchez, Jose Hector Sanchez Mijangos, Pablo Serrano Sanson, Juan Alfredo Tamayo y Orozco, Eloisa Tellez Chavez, Alejandro Valdes Cepeda, Luis Venegas Carrillo, Juan Villagordoa Mesa, Rolando Zamarripa Escobedo, John Baker, Paul Noonan, Russell Scott, Robert Walker, Edward Watson, Michael Williams, Simon Young, Zaynab Abejuela, Jeimeen Agra, Grace Aquitania, Clodoaido Caringal, Rhea Severina Comia, Lalaine Delos Santos, Olivert Gomez, Cecilia Jimeno, Gerry Tan, Marsha Tolentino, Christy Yao, Yvette Ethel Yap, Ma. Dovie Lallaine Ygpuara, Renata Bijata-Bronisz, Lucyna Hotlos, Andrzej Januszewicz, Barbara Kaczmarek, Anna Kaminska, Lech Lazuka, Andrzej Madej, Stanislaw Mazur, Dorota Mlodawska-Choluj, Michal Nowicki, Grazyna Orlowska-Kowalik, Grazyna Popenda, Barbara Rewerska, Dariusz Sowinski, Liliana Monica Angelescu, Veronica Anghel, Rodica-Ioana Avram, Mihaela-Magdalena Busegeanu, Adriana Cif, Dana Cosma, Carmen Crisan, Luiza Despina Demian, Ioana Emilia Ferariu, Ildiko Halmagyi, Nicolae Hancu, Mircea Munteanu, Doru Negru, Adriana Gabriela Onaca, Ligia Petrica, Amorin Remus Popa, Aurelian-Emil Ranetti, Cristian Serafinceanu, Cristina Toarba, Alina Agafyina, Olga Barbarash, Olga Barysheva, Daniil Chizhov, Vladimir Dobronravov, Irina Glinkina, Elena Grineva, Vladimir Khirmanov, Elena Kolmakova, Tatiana Koroleva, Liudmila Kvitkova, Viacheslav Marasaev, Ashot Mkrtumyan, Tatiana Morugova, Galina Nagibovich, Oleg Nagibovich, Sergei Nedogoda, Irina Osipova, Tatiana Raskina, Yulia Samoylova, Olga Sazonova, Minara Shamkhalova, Elena Shutemova, Yuriy Shwartz, Oleg Uriasyev, Sergey Vorobyev, Anna Zateyshchikova, Dmitry Zateyshshikov, Tatyana Zykova, Slobodan Antic, Miodrag Djordjevic, Aleksandra Kendereski, Katarina Lalic, Nebojsa Lalic, Vesna Popovic-Radinovic, Jana Babikova, Olga Benusova, Ingrid Buganova, Jan Culak, Andrej Dzupina, Jana Dzuponova, Peter Fulop, Adriana Ilavska, Emil Martinka, Zuzana Ochodnicka, Daniel Pella, Iveta Smatanova, Fayzal Ahmed, Aysha Badat, Johannes Breedt, Lawrence Distiller, Vimladhevi Govender, Ravendran Govender, Mukesh Joshi, Jaco Jurgens, Gulam Latiff, Landman Lombard, Mohamed Mookadam, Nomangesi Ngcakani, Hendrik Nortje, Helena Oosthuizen, Larisha Pillay-Ramaya, Hans Prozesky, Jeevren Reddy, Paul Rheeder, Mary Seeber, Young Min Cho, In-Kyung Jeong, Sin Gon Kim, Yeong Hoon Kim, Hyuk-Sang Kwon, Min Jeong Kwon, Byung-Wan Lee, JungEun Lee, Moon-Kyu Lee, Moon-Suk Nam, Kook-Hwan Oh, Cheol- Young Park, Sun-Hee Park, Kun Ho Yoon, Pere Alvarez Garcia, Luis Asmarats Mercadal, Clara Barrios, Fernando Cereto Castro, Secundino Cigarran Guldris, Marta Dominguez Lopez, Jesus Egido de los Rios, Gema Fernandez Fresnedo, Antonio Galan Serrano, Isabel Garcia, Francisco Javier Gonzalez Martinez, Jose Esteban Jodar Gimeno, Manuel Lopez Mendoza, Tamara Malek Marin, Cristobal Morales Portillo, Maria Antonia Munar Vila, Manuel Muñoz Torres, Javier Nieto Iglesias, Jonay Pantoja Perez, Merce Perez Vera, Jose M. Portoles Perez, María Angustias Quesada Simón, Rafael Simo Canonge, Alfonso Soto Gonzalez, Manel Terns Riera, Francisco Jose Tinahones Madueno, Mercedes Velo Plaza, Chwen-Tzuei Chang, Lee-Ming Chuang, Te-Lin Hsia, Chang-Hsun Hsieh, Chih-Ching Lin, Yung- Chuan Lu, Wayne H-H Sheu, Olga Barna, Svitlana D. Bilyk, Volodymyr Botsyurko, Iryna Dudar, Ivan Fushtey, Olga Godlevska, Oleksandr Golovchenko, Olga Gyrina, Anatoliy Kazmirchuk, Iuliia Komisarenko, Oleksii Korzh, Nonna Kravchun, Oleg Legun, Borys Mankovskyy, Liliya Martynyuk, Yuriy Mostovoy, Nataliia Pashkovska, Larysa Pererva, Tetyana Pertseva, Oleksandr Samoylov, Ivan Smirnov, Yevgeniya Svyshchenko, Halyna Tomashkevych, Ivan Topchii, Nadiya Tryshchuk, Vira Tseluyko, Vadym Vizir, Maryna Vlasenko, Tetiana Zlova, Liliia Zub, Salah Abusnana, Mohamed Railey, Kamal Abouglila, Paul Ainsworth, Zishan Ali, Vijayaraman Arutchelvam, Maria Barnard, Srikanth Bellary, Emyr Davies, Mark Davies, Simon Davies, Alison Dawson, Mohsen El Kossi, Patrick English, Donald Fraser, Luigi Gnudi, Anthony Gunstone, Timothy Hall, Wasim Hanif, Alan Jackson, Andrew Johnson, Franklin Joseph, Singhan Krishnan, Mick Kumwenda, Iain MacDougall, Paul Nixon, Joseph O'Hare, Sam Philip, Shenaz Ramtoola, Manish Saxena, Davesh Sennik, Godwin Simon, Baldev Singh, Jeffrey Stephens, Anna Strzelecka, Rehan Symonds, Wayne Turner, Mona Wahba, John Wakeling, David Wheeler, Peter Winocour, Joseph Abdallah, Raied Abdullah, Matthew Abramowitz, Idalia Acosta, Joseph Aiello, Laura Akright, Ayim Akyea-Djamson, Rajendran Alappan, Radica Alicic, Amer Al-Karadsheh, Dale Crawford Allison, Carlos Arauz-Pacheco, Shahabul Arfeen, Ahmed Arif, Moogali Arvind, Naveen Atray, Ahmed Awad, Peggy Barnhill, Elizabeth Barranco, Carlos Barrera, Matthew Beacom, Venkata Behara, Diogo Belo, Rhonda Bentley-Lewis, Ramon Berenguer, Lidia Bermudez, Marializa Bernardo, Mihaela Biscoveanu, Cynthia Bowman-Stroud, Donald Brandon, Osvaldo Brusco, Robert Busch, Yamil Canaan, Alicia Chilito, Tom Christensen, Cynthia Christiano, Elena Christofides, Caroucel Chuateco, Kenneth Cohen, Robert Cohen, Debbie Cohen-Stein, Charles Cook, Daniel Coyne, Nizar Daboul, Riad Darwish, Adarsh Daswani, Kenneth Deck, Cyrus Desouza, Devasmita Dev, Monika Dhillon, Sohan Dua, Frank Eder, Ana Maria Elosegui, Mohamed El-Shahawy, John Ervin, Alberto Esquenazi, John Evans, Steven Fishbane, Juan Frias, Eugenia Galindo-Ramos, Claude Galphin, Adline Ghazi, Enrique Gonzalez, David Gorson, Anupama Gowda, Barbara Greco, Stephen Grubb, Rakesh Gulati, Jamal Hammoud, Stuart Handelsman, Israel Hartman, Kenneth Hershon, Daniel Hiser, George Hon, Radu Jacob, Maria Jaime, Aamir Jamal, Charles Kaupke, Gerald Keightley, Elizabeth Kern, Rakhi Khanna, Zeid Khitan, Sun Kim, Nelson Kopyt, Csaba Kovesdy, Gopal Krishna, Jeffrey (Jay) Kropp, Amrendra Kumar, Jayant Kumar, Neil Kumar, Jorge Kusnir, Wendy Lane, Mary Lawrence, Lawrence Lehrner, John Lentz, Dennis Levinson, Derek Lewis, Kenneth Liss, Andreas Maddux, Hiralal Maheshwari, Sreedhar Mandayam, Isam Marar, Bhasker Mehta, John Middleton, Jorge Mordujovich, Ramon Moreda, Moustafa Moustafa, Samuel Mujica Trenche, Mohanram Narayanan, Javier Narvarte, Tareq Nassar, George Newman, Brian Nichol, Philip Nicol, Josier Nisnisan, A. Kaldun Nossuli, Chamberlain Obialo, Sarah Olelewe, Michael Oliver, Andrew O'Shaughnessy, John Padron, Rohit Pankhaniya, Reginald Parker, Devesh Patel, Gnyandev Patel, Nina Patel, Humberto Pavon, Armando Perez, Carlos Perez, Alan Perlman, Karlton Pettis, Walter Pharr, Andrea Phillips, Raman Purighalla, Luis Quesada-Suarez, Rajiv Ranjan, Sanjeev Rastogi, Jakkidi Reddy, Marc Rendell, Lisa Rich, Michael Robinson, Hector Rodriguez, Sylvia Rosas, Fadi Saba, Rallabhandi Sankaram, Ravi Sarin, Robert Schreiman, David Scott, Mohamed Sekkarie, John Sensenbrenner, Muhammad Shakeel, Michael Shanik, Sylvia Shaw, Stephen Smith, Richard Solomon, Amy Sprague, Leslie Spry, Pusadee Suchinda, Senan Sultan, Prasanth Surampudi, Sherry Sussman, Anjanette Tan, Antonio Terrelonge, Michael Thompson, Fernando Trespalacios, Bruce Trippe, Pilar Trueba, Marcel Twahirwa, John Updegrove, Peter Van Buren, Mark Vannorsdall, Freemu Varghese, Pedro Velasquez-Mieyer, Sailaja Ventrapragada, Goga Vukotic, Khurram Wadud, Mark Warren, Henry Watson, Ronald Watts, Daniel Weiner, James Welker, Jean Welsh, Shelley Williams, and Michelle Zaniewski-Singh

Subjects
age, diabetes, Nephrology, kidney outcomes, sex, Diabetic kidney disease, canagliflozin, cardiovascular outcomes, chronic kidney disease, sodium/glucose cotransporter 2 inhibitors
Abstract

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Published
2023

19. Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study

Author

Blandine Tramunt, Emmanuel Disse, Nicolas Chevalier, Lyse Bordier, Laurent Cazals, Olivier Dupuy, Michel Marre, Odette Matar, Laurent Meyer, Chloé Noilhan, Caroline Sanz, Paul Valensi, Fritz-Line Velayoudom, Jean-François Gautier, and Pierre Gourdy

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system.A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbAIDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbAWhile providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.

Published
2022

20. Les auteurs

Author

Geneviève, Plu-Bureau, primary, Brigitte, Raccah-Tebeka, additional, Florence,, Trémollières, additional, Vered, Abitbol, additional, Gabriel, André, additional, Jean-François, Arnal, additional, Anne, Bachelot, additional, Clarence, de Belilovsky, additional, Claire, Beylot, additional, Astrid, Blom, additional, Léon, Boubli, additional, Jean-Louis, Bourges, additional, Antoine, Bourret, additional, Gérard, Boutet, additional, Léopoldine, Bricaire, additional, Sophie, Christin-Maitre, additional, Myriam, Dridi Sophie, additional, Caroline, Dubertret, additional, Coralie, Fontaine, additional, Anne, Gompel, additional, Pierre, Gourdy, additional, Virginie, Grouthier, additional, Naima, Hamdaoui, additional, Claude, Hocké, additional, Justine, Hugon-Rodin, additional, Corinne, Lallam, additional, Véronique, Le Guern, additional, Françoise, Lenfant, additional, Brigitte, Letombe, additional, Patrice, Lopes, additional, Sandra, Ly, additional, Anne-Laure,, Madika, additional, Lorraine, Maitrot-Mantelet, additional, Ianis, Marciceau, additional, Pierre, Mares, additional, Virginie, Monnet Corti, additional, Claire, Mounier-Vehier, additional, Emmanuelle, Noirrit-Esclassan, additional, Florence, Pasquier, additional, Olivia, Pietri, additional, Isabelle, Ray-Coquard, additional, Geoffroy, Robin, additional, Christine, Rousset-Jablonski, additional, Sarah, Tebeka, additional, Philippe, Touraine, additional, Blandine, Tramunt, additional, and Marie-Cécile, Valéra, additional

Published
2019
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21. Nocturnal hypoglycemia is underdiagnosed in older people with insulin‐treated type 2 diabetes: The <scp>HYPOAGE</scp> observational study

Author

Anne‐Sophie Boureau, Béatrice Guyomarch, Pierre Gourdy, Ingrid Allix, Cédric Annweiler, Nathalie Cervantes, Guillaume Chapelet, Isabelle Delabrière, Sophie Guyonnet, Rachel Litke, Marc Paccalin, Alfred Penfornis, Pierre‐Jean Saulnier, Matthieu Wargny, Samy Hadjadj, Laure de Decker, and Bertrand Cariou

Subjects
Geriatrics and Gerontology
Published
2023

22. Cost-Effectiveness Evaluation of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Study

Author

Michael, Mounié, Nadège, Costa, Pierre, Gourdy, Christelle, Latorre, Solène, Schirr-Bonnans, Jean-Marc, Lagarrigue, Henri, Roussel, Jacques, Martini, Jean-Christophe, Buisson, Marie-Christine, Chauchard, Jacqueline, Delaunay, Soumia, Taoui, Marie-France, Poncet, Valeria, Cosma, Sandrine, Lablanche, Magali, Coustols-Valat, Lucie, Chaillous, Charles, Thivolet, Caroline, Sanz, Alfred, Penfornis, Benoît, Lepage, Hélène, Colineaux, Hélène, Hanaire, Laurent, Molinier, Marie-Christine, Turnin, Université Fédérale Toulouse Midi-Pyrénées, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), MSA Midi-Pyrénées Nord [Montauban] (MSA-MPN), Directions régionales du Service médical Occitanie [Toulouse] (DRSM / CNAM), DIAMIP Network [Toulouse] ( Association Diabète Occitanie), Ecole Nationale Supérieure d'Electrotechnique, d'Electronique, d'Informatique, d'Hydraulique et de Télécommunications (ENSEEIHT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Clinique Claude Bernard - ELSAN [Albi] (CCBE), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Clinique Ambroise Paré - ELSAN [Toulouse] (CAPE), Centre hospitalier universitaire de Nantes (CHU Nantes), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Clinique Pasteur [Toulouse], Centre Hospitalier Sud Francilien, Educ@dom Study Group, and CarMeN, laboratoire

Subjects
[SDV] Life Sciences [q-bio], Telemonitoring, Educ@dom, Economic assessment, Tele-education, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Internal Medicine, Lifestyle management, Type 2 diabetes, Cost-effectiveness
Abstract

Erratum inCorrection to: Cost-Effectiveness Evaluation of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Study.Mounié M, Costa N, Gourdy P, Latorre C, Schirr-Bonnans S, Lagarrigue JM, Roussel H, Martini J, Buisson JC, Chauchard MC, Delaunay J, Taoui S, Poncet MF, Cosma V, Lablanche S, Coustols-Valat M, Chaillous L, Thivolet C, Sanz C, Penfornis A, Lepage B, Colineaux H, Hanaire H, Molinier L, Turnin MC; Educ@dom Study Group, Benhamou PY, Rodier M, Ayon F, Puel-Olivier F, Fontaine S, Perron M, Arrivié J, Cousty-Pech F, Rouby C, Lafon F, Moura I.Diabetes Ther. 2022 May;13(5):1131-1132. doi: 10.1007/s13300-022-01248-6.PMID: 35316510 Free PMC article. No abstract available.; International audience; INTRODUCTION: Telemedicine programs using health technological innovation to remotely monitor the lifestyles of patients with type 2 diabetes (T2D) can improve glycaemic control and thus reduce the incidence of complications as well as management costs. In this context, an assessment was made of the 1-year and 2-year cost-effectiveness of the EDUC@DOM telemonitoring and tele-education program. METHODS: The EDUC@DOM study was a multicentre randomized controlled trial conducted between 2013 and 2017 that compared a telemonitoring group (TMG) to a control group (CG) merged with health insurance databases to extract economic data on resource consumption. Economic analysis was performed from the payer perspective, and direct costs and indirect costs were considered. The clinical outcome used was the intergroup change in glycated haemoglobin (HbA1c) levels from baseline. Missing economic data were imputed using multiple imputation, and fitted values from a generalized linear mixed model were used to calculate the incremental cost-effectiveness ratio (ICER). Bootstrapped 95% confidence ellipses were drawn in the cost-effectiveness plan. RESULTS: The main analysis included data from 256 patients: 126 in the TMG and 130 in the CG. Incremental costs over 1 and 2 years were equal to €2129 and €5101, respectively, in favour of the TMG. Once imputed and adjusted for confounding factors, the TMG trends to a 21% cost decrease over 1 and 2 years of follow-up (0.79 [0.58; 1.08], p = 0.1452 and 0.79 [0.61; 1.03], p = 0.0879, respectively). The EDUC@DOM program led to a €1334 cost saving and a 0.17 decrease in HbA1c over 1 year and a €3144 cost saving and a 0.14 decrease in HbA1c over 2 years. According to the confidence ellipse, EDUC@DOM was a cost-effective strategy. CONCLUSION: This study provides additional economic information on telemonitoring and tele-education programs to enhance their acceptance and promote their use. In the light of this work, the EDUC@DOM program is a cost-saving strategy in T2D management. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Database on 27 September 2013 under no. NCT01955031 and bears ID-RCB no. 2013-A00391-44.

Published
2022

23. Prise de position de la Société Francophone du Diabète (SFD) sur les stratégies d’utilisation des traitements anti-hyperglycémiants dans le diabète de type 2 – 2021

Author

Tiphaine Vidal-Trecan, Bernard Bauduceau, Sophie Jacqueminet, Jacques Philippe, Patrice Darmon, Bruno Guerci, Charles Thivolet, Lyse Bordier, André Scheen, Pierre Gourdy, Alfred Penfornis, and Bruno Detournay

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

24. Does Gender Influence the Effectiveness and Safety of Insulin Glargine 300 U/ml in Patients with Uncontrolled Type 2 Diabetes? Results from the REALI European Pooled Analysis

Author

Celine Mauquoi, Riccardo C. Bonadonna, Gregory Bigot, Pierre Gourdy, Nick Freemantle, Alice Ciocca, Didac Mauricio, Dirk Müller-Wieland, and Mireille Bonnemaire

Subjects
Insulin glargine 300 U/ml, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, Pooled analysis, Internal medicine, Diabetes mellitus, Glycaemic control, Internal Medicine, medicine, Gender differences, Myocardial infarction, Original Research, Insulin glargine 300 U, Insulin glargine, business.industry, Incidence (epidemiology), nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, ml, Europe, business, Body mass index, medicine.drug
Abstract

Diabetes therapy 13(1), 57-73 (2022). doi:10.1007/s13300-021-01179-8, Published by Springer Healthcare Communications, New York, NY [u.a.]

Published
2021

25. Glycaemic Control in People with Type 2 Diabetes Mellitus Switching from Basal Insulin to Insulin Glargine 300 U/ml (Gla-300): Results from the REALI Pooled Database

Author

Dirk Müller-Wieland, Nick Freemantle, Riccardo C. Bonadonna, Celine Mauquoi, Gregory Bigot, Mireille Bonnemaire, Pierre Gourdy, and Didac Mauricio

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes.Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI. Of the 4463 participants, 1282 (28.7%) were pre-treated with neutral protamine Hagedorn (NPH) insulin and 2899 (65.0%) with BI analogues (BIAs), and 282 (6.3%) had undetermined prior BI.There were no meaningful differences in baseline characteristics between subgroups, except for a higher prevalence of diabetic neuropathy in the NPH subgroup (21.6% versus 7.8% with BIAs). Mean ± standard deviation haemoglobin A1c (HbA1c) decreased from 8.73 ± 1.15% and 8.35 ± 0.95% at baseline to 7.71 ± 1.09% and 7.82 ± 1.06% at week 24 in the NPH and BIA subgroups, respectively. Least squares (LS) mean change in HbA1c was - 0.85% (95% confidence interval - 0.94 to - 0.77) in NPH subgroup and - 0.70% (- 0.77 to - 0.64) in BIA subgroup, with a LS mean absolute difference between subgroups of 0.16 (0.06-0.26; p = 0.002). Gla-300 mean daily dose was slightly increased at week 24 by 0.07 U/kg/day (approximately 6 U/day) in both subgroups. Incidences of symptomatic and severe hypoglycaemia were low, without body weight change.Irrespective of previous BI therapy (NPH insulin or BIAs), switching to Gla-300 improved glycaemic control without weight gain and with low symptomatic and severe hypoglycaemia incidences. However, a slightly greater glucose-lowering effectiveness was observed in people pre-treated with NPH insulin.

Published
2022

26. Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19: The CORONADO, ABCD COVID-19 UK national audit and AMERICADO study groups

Author

Samy, Hadjadj, Pierre-Jean, Saulnier, Yue, Ruan, Xu, Zhu, Renee, Pekmezaris, Michel, Marre, Jean Michel, Halimi, Matthieu, Wargny, Rustam, Rea, Pierre, Gourdy, Bertrand, Cariou, Alyson K, Myers, and Kamlesh, Khunti

Abstract

To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19.We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer.Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID-19.

Published
2022

27. 807-P: Glycemic Control in People with Type 2 Diabetes (PWT2D) Switching from NPH to Insulin Glargine 300 U/mL (Gla-300) : REALI Pooled Database

Author

DIRK MÜLLER-WIELAND, NICK FREEMANTLE, RICCARDO C. BONADONNA, CELINE MAUQUOI, GREGORY BIGOT, MIREILLE BONNEMAIRE, PIERRE GOURDY, and DIDAC MAURICIO

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

The effectiveness of Gla-300 in PWT2D switching from NPH is not widely documented. REALI database combines individual data from 14 European studies in T2D. We analyzed data from PWT2D uncontrolled on prior basal insulin (BI) , 1282 switching from NPH and 2899 from other non-NPH BIs (mainly glargine 100 U/mL, 67%) to Gla-300. In the NPH group, mean±SD age was 63±9.4 years, BMI 32.5±5.8 kg/m2, and median diabetes duration 12 years. The majority previously used biguanides (71%) , followed by sulfonylureas (20%) , and dipeptidyl peptidase 4 inhibitors (18%) . HbA1c markedly improved after a 24-week Gla-300 therapy (Figure 1A) . Mean±SD fasting plasma glucose (FPG) decreased from 188.8±55.9 mg/dL at Baseline to 143.3±45.5 at Week 24. Gla-300 was started at a mean dose of 29.4 U/day and titrated up to 35.6 at Week 24, with no body weight (BW) change. In the non-NPH BI group, baseline characteristics were comparable to those in the NPH group, except for higher baseline HbA1c and FPG in the latter. Figure 1B illustrates HbA1c improvement in the non-NPH BI group, at a mean Gla-300 starting dose of 35.4 U/day increasing to 41.7 at Week 24, with no BW change. Hypoglycemia was similarly low in both groups. This analysis shows that PWT2D, previously uncontrolled on BI, benefited from switching to Gla-300 in terms of HbA1c improvement, and this was especially observed in those previously treated with NPH. Disclosure D.Müller-wieland: Advisory Panel; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. N.Freemantle: Consultant; Novo Nordisk, Research Support; Aimmune, ALK-Abelló A/S, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Sanofi, Vertex Pharmaceuticals Incorporated, Speaker's Bureau; Abbott. R.C.Bonadonna: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. C.Mauquoi: None. G.Bigot: None. M.Bonnemaire: Employee; Sanofi. P.Gourdy: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma, Novo Nordisk, Sanofi, Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. D.Mauricio: Advisory Panel; Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Speaker's Bureau; Almirall, S.A., Esteve, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. Funding Sanofi

Published
2022

28. Impact of Age on the Effectiveness and Safety of Insulin Glargine 300 U/mL: Results from the REALI European Pooled Data Analysis

Author

Didac Mauricio, Riccardo C. Bonadonna, Nick Freemantle, Dirk Müller-Wieland, Gregory Bigot, Mireille Bonnemaire, Pierre Gourdy, Celine Mauquoi, and Alice Ciocca

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, mL, Pooled analysis, 03 medical and health sciences, Age, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Glycaemic control, Internal Medicine, medicine, Pooled data, Original Research, Insulin glargine 300 U/mL, Insulin glargine 300 U, Insulin glargine, business.industry, Incidence (epidemiology), nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, Confidence interval, Europe, Older adults, Hypoglycaemia, business, medicine.drug
Abstract

Diabetes therapy 12(4), 1073-1097 (2021). doi:10.1007/s13300-021-01030-0, Published by Springer Healthcare Communications, New York, NY [u.a.]

Published
2021

29. The INSPIRE research initiative: a program for GeroScience and healthy aging research going from animal models to humans and the healthcare system

Author

Louis Casteilla, Sandrine Andrieu, Pierre Payoux, Isabelle Ader, Cédric Dray, Bruno Vellas, Luc Pénicaud, Roland S. Liblau, Nathalie Vergnolle, P. de Souto Barreto, Yves Rolland, Sophie Guyonnet, Nicolas Fazilleau, Pierre Gourdy, Noélie Davezac, Angelo Parini, Philippe Valet, Claire Rampon, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte, Region Hauts-de-France, Region Nouvelle-Aquitaine (Reference number: 1901175), European Regional Development Fund (ERDF) (Project number: MP0022856), Inspire Chairs of Excellence - Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, SEGUIN, Nathalie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI)

Subjects
0301 basic medicine, Gerontology, Gerosciences, medicine.medical_specialty, Research program, Biomedical Research, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Delivery of Health Care, MESH: Geriatrics, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, MESH: Animals, intrinsic capacity, 030212 general & internal medicine, Healthy aging, Aged, MESH: Aged, Geriatrics, MESH: Humans, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geroscience, business.industry, MESH: Biomedical Research, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public health, MESH: Healthy Aging, General Medicine, Risk factor (computing), 3. Good health, Integrated care, 030104 developmental biology, MESH: Models, Animal, biological aging, Models, Animal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Translational science, business, Delivery of Health Care
Abstract

International audience; Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.

Published
2020

30. COVID-19 and Diabetes Outcomes: Rationale for and Updates from the CORONADO Study

Author

Sarra Smati, Blandine Tramunt, Matthieu Wargny, Pierre Gourdy, Samy Hadjadj, and Bertrand Cariou

Subjects
SARS-CoV-2, Endocrinology, Diabetes and Metabolism, Internal Medicine, Diabetes Mellitus, COVID-19, Humans, Pandemics, Respiration, Artificial
Abstract

In France, in order to describe the phenotypic characteristics of patients with diabetes hospitalized for coronavirus disease-2019 (COVID-19) and to identify the prognostic factors in this specific population, the CORONADO (CORONAvirus and Diabetes Outcomes) study was launched. This review will summarize the key findings from the CORONADO study and put them in perspectives with others studies published on the subject.For almost 2 years, the new SARS-CoV-2 (Severe Acute Respiratory Syndrome-CoronaVirus-2), which causes COVID-19, has spread all around the world leading to a pandemic. From the first epidemiological reports, diabetes mellitus has rapidly emerged as a major risk factor associated with severe forms of COVID-19 but few data were available about diabetes characteristics in hospitalized people with COVID-19. Between March 10 and April 10, 2020, 2951 patients were included in 68 centers throughout the national territory, including overseas territories. In the CORONADO study, the primary outcome was a composite endpoint combining invasive mechanical ventilation (IMV) and/or death within day 7 (D7). Secondary outcomes included death, IMV, intensive care unit (ICU) admission, and hospital discharge, all considered within D7 and day 28 (D28). The primary outcome occurred in 29.0% participants within D7 following hospital admission. Within D28, the end of the follow-up period, the mortality rate was 20.6%, while 50.2% of patients were discharged. In multivariable analysis, advanced age, microvascular complications, treatment with insulin or statin prior to admission, dyspnea on admission, as well as biological markers reflecting the severity of the infection (high levels of transaminases, leukocytes and CRP, and low platelet levels) were associated with an increased risk of death. Several exploratory analyses were performed to clarify the influence of some parameters such as weight status, sex, type of diabetes, and some routine drugs, including metformin or statins.

Published
2022

31. History of bariatric surgery and COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study

Author

Natacha Germain, Matthieu Wargny, François Pattou, Claire Blanchard, Sophie Borot, Lyse Bordier, Dominique Seret-Bégué, Edith Bigot-Corbel, Bruno Vergès, Bertrand Cariou, Christine Coffin-Boutreux, Céline Gonfroy-Leymarie, Olivier Bourron, Laurent Meyer, Ronan Roussel, Pierre Gourdy, Gaëtan Prévost, Béatrice Guyomarch, Anne Dutour, Charles Thivolet, Matthieu Pichelin, Tanguy Perennec, Blandine Tramunt, Sarra Smati, Samy Hadjadj, Cyrielle Caussy, CarMeN, laboratoire, Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), CENTRE HOSPITALIER PÉRIGUEUX (CHP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier René Dubos [Pontoise], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Gonesse (CHU Gonesse), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), FCRIN/FORCE Network, Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Diabetes duration, medicine.medical_specialty, animal structures, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Bariatric Surgery, Type 2 diabetes, Endocrinology, COVID‐19, Diabetes mellitus, medicine, Humans, In patient, Viral, Brief Cutting Edge Report, Retrospective Studies, Mechanical ventilation, Diabetes Mellitus, Nutrition and Dietetics, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Surgery, Type 2 Diabetes, [SDV] Life Sciences [q-bio], Metabolic and Bariatric Surgery, Diabetes Mellitus, Type 2, covid-19, RNA, Viral, RNA, Observational study, business, Body mass index, Type 2
Abstract

International audience; OBJECTIVE: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS.

Published
2022

32. Prise de position de la Société Francophone du Diabète (SFD) sur la prise en charge médicamenteuse de l’hyperglycémie du patient diabétique de type 2 – 2019

Author

Patrice Darmon, Bernard Bauduceau, Lyse Bordier, Bernard Charbonnel, Emmanuel Cosson, Bruno Detournay, Pierre Fontaine, André Grimaldi, Pierre Gourdy, Bruno Guerci, Hélène Hanaire, Alfred Penfornis, and André Scheen

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published
2019

33. Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative

Author

Bertrand, Cariou, Matthieu, Wargny, Anne-Sophie, Boureau, Sarra, Smati, Blandine, Tramunt, Rachel, Desailloud, Maylis, Lebeault, Coralie, Amadou, Deborah, Ancelle, Beverley, Balkau, Lyse, Bordier, Sophie, Borot, Muriel, Bourgeon, Olivier, Bourron, Emmanuel, Cosson, Martin, Eisinger, Céline, Gonfroy-Leymarie, Jean-Baptiste, Julla, Lucien, Marchand, Laurent, Meyer, Dominique, Seret-Bégué, Dominique, Simon, Ariane, Sultan, Charles, Thivolet, Anne, Vambergue, Camille, Vatier, Patrice, Winiszewski, Pierre-Jean, Saulnier, Bernard, Bauduceau, Pierre, Gourdy, Samy, Hadjadj, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Santé publique - Clinique des données [CHU Nantes] (Pôle Hospitalo-Universitaire 11), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sud Francilien, Université Paris-Saclay, CH Le Havre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Hôpital Avicenne [AP-HP], 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, Centre Intégré Nord Francilien de l'Obésité (CINFO), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier René Dubos [Pontoise], Hôpital Lariboisière-Fernand-Widal [APHP], Centre hospitalier Saint Joseph - Saint Luc [Lyon], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier de Gonesse, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Société Francophone du Diabète, Partenaires INRAE, CHU Lille, CHU Saint-Antoine [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), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), and MORNET, Dominique

Subjects
Male, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Diabetes, Charlson index, COVID-19, Comorbidity, Prognosis, [SDV] Life Sciences [q-bio], Death, Cohort Studies, Internal Medicine, Diabetes Mellitus, Humans, Female, Invasive mechanical ventilation
Abstract

International audience; Aims/hypothesis: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question.Methods: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes.Results: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p

Published
2021

34. Author response for 'Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study'

Author

null A Diallo, null M Pichelin, null M Wargny, null P Gourdy, null JB Bonnet, null S Hadjadj, null B Cariou, null A Sultan, null F Galtier, null Matthieu Wargny, null Pascale Mahot, null Bertrand Cariou, null Samy Hadjadj, null Matthieu Pichelin, null Anne‐Laure Fournier‐Guilloux, null Nicolas Mauduit, null Edith Bigot‐Corbel, null Anne‐Sophie Boureau, null Laure Dekcer, null Audrey Ernould, null Claire Primot, null Anne Seguin, null Marielle Joliveau, null Sonia Pouvreau, null Chloé FOURNIER, null Jeremy Thureau, null Edith Fonteneau, null Pamela Hublain, null Chu Nantes, null Carole Agasse, null Mathilde DE Kergaradec, null Vincent Minville, null Fanny Vardon‐Bounes, null Guillaume Martin‐Blondel, null Pierre Gourdy, null Blandine Tramunt, null Marie‐Christine Turnin, null Hélène Hanaire, null Jean‐Michel Mansuy, null Didier Fabre, null Marie‐Blanche Arhainx, null Laurent Cazals, null Laure Combes, null Emmanuelle Lami, null Mallory Cianferani, null Bruno Megarbane, null Pierre Leroy, null Jean‐François Gautier, null Tiphaine Vidal‐Trecan, null Jean‐Pierre Riveline, null Jean‐Louis Laplanche, null Stéphane Mouly, null Louis Potier, null Ronan Roussel, null Malak Taher, null Yawa Abouleka, null Fetta Yaker, null Aurelie Carlier, null Anne Boutten, null Marilyne Hallot‐Feron, null Fadila Mourah, null Charles Thivolet, null Emilie Blond, null Muriel Rolland, null Josep Verdecho Mendez, null Marine Alexandre, null Julien Pottecher, null Emilie Richer, null Laurent Meyer, null Florina Luca, null Jean‐Marc Lessinger, null Thibault Bahougne, null Bruno Guerci, null Lisa Ludwig, null Siham Benzirar, null Catherine Malaplate, null Thierry Matton, null Julien Poissy, null Karine Faure, null Pierre Fontaine, null Florence Baudoux, null Anne Vambergue, null Jean David Pekar, null Marc Lambert, null Cécile Yelnik, null Amélie Bruandet, null Laurent Petit, null Didier Neau, null Vincent Rigalleau, null Annie Berard, null Amandine Galioot, null Remy Coudroy, null Arnaud Thille, null René Robert, null France Roblot‐Cazenave, null Blandine Rammaert, null Pierre Jean Saulnier, null Xavier Piguel, null Nesrine Benhenda, null Camille Husson, null Celine Olivier, null Florence Torremocha, null Mathilde Fraty, null Marie Flamen d'assigny, null Aurelie Miot, null Valentin Bossard, null Kada Klouche, null Alain Makinson, null Ariane Sultan, null Jean‐Baptiste Bonnet, null Vincent Foulongne, null Florence Galtier, null Cécile Aubron, null Séverine Ansart, null Véronique Kerlan, null Pascale Quiniou, null Jean‐Luc Carre, null Stéphane Quesnot, null Bruno Laviolle, null Carole Schwebel, null Olivier Epaulard, null Pierre‐Yves Benhamou, null Cécile Betry, null Anne‐Laure Borel, null Sandrine Lablanche, null Dorra Guergour, null Catherine Duclos, null Emmanuel Cosson, null Erwan Guyot, null Aurore Deniau, null Phucthutrang Nguyen, null Yves Reznik, null Michael Joubert, null Stéphane Allouche, null Lydia Guittet, null Steven Grange, null Manuel Etienne, null Gaëtan Prévost, null Valéry Brunel, null Jean‐Christophe Lagier, null Didier Raoult, null Anne Dutour, null Bénédicte Gaborit, null Sandrine Boulllu, null Patrice Darmon, null Adèle Lasbleiz, null Mathieu Cerino, null Fanny Romain, null Marie Houssays, null Jean Pierre Quenot, null Lionel Piroth, null Bruno Vergès, null Laurence Duvillard, null Bernard Bonnotte, null Alain Mercat, null Vincent Dubee, null Ingrid Allix, null Patrice Rodien, null Robin Dhersin, null Maylis Lebeault, null Wojciech Trzepizur, null Jocelyne Loison, null Antoine Brangier, null Pierre Asfar, null Pascal Reynier, null Françoise Larcher, null Françoise Joubaud, null Marie‐Rita Andreu, null Geoffrey Urbanski, null Laurent Hubert, null Cedric Annweiler, null Jean Dellamonica, null Johan Courjon, null Nicolas Chevalier, null Giulia Chinetti, null Magda Chafai, null Bruno Mourvillier, null Firouze Bani‐Sadr, null Sarra Barraud, null Brigitte Delemer, null Philippe Gillery, null Pascale Labedade, null Amélie Chabrol, null Alfred Penfornis, null Catherine Petit, null Coralie Amadou, null Maxime Adler, null Clément Dubost, null Pierre‐Louis Conan, null Lyse Bordier, null Franck Ceppa, null Cyril Garcia, null Mathilde Sollier, null Olivier Dupuy, null Sophie Laplance, null Olivier Billuart, null Marie Joseph Aroulanda, null Frédérique Olivier, null Florence Ayon, null Nathalie Wilhelm, null Loic Epelboin, null Nadia Sabbah, null Aurelie Charpin, null Pierre Squara, null Olivier Belliard, null Claude Dubois, null Michel Marre, null Johann Auchabie, null Roxane Courtois, null Thierry Duriez, null Tiphaine Mergey, null Laura Vallee, null Laetitia Seguin, null Abdallah Al‐Salameh, null Jean‐Philippe Lanoix, null Sandrine Soriot‐Thomas, null Anne‐Marie Bourgeois‐Descouls, null Rachel Desailloud, null Natacha Germain, null Bogdan Galusca, null Gwenaelle Belleton, null Nesrine Marouani, null Delia Palaghiu, null Amira Hammour, null Fernando Berdaguer, null Thimothée Klopfenstein, null Hajer Zayet, null Patrice Winiszewski, null Marie Zanusso, null Pauline Garnier, null Ingrid Julier, null Karim Hamzaoui, null Sophie Marty‐Gres, null Tarik Sadki, null Lucile Cadot, null Jean‐Louis Dubost, null Céline Gonfroy, null Catherine Campinos, null Pascale Martres, null Marie Pierre Coulhon, null Nicolas Allou, null Marwa Bachir, null Stella Hoang, null Candice Kembellec, null Olivia Suply, null Fatima Kharcha, null Anne‐Claire Devouge, null Anna Flaus‐Furmanuk, null Isabelle Madeline, null Vincent Ehinger, null Sophie Bastard, null Loic Raffray, null Frederic Renou, null Aude Bojarski, null Caroline Paul, null Karine Borsu, null Angelique Gorlin, null Servane Bernardo, null Carole Truong Ut, null Stephane Renaud, null Antoine Vignoles, null Emilie Foch, null Laurie Masse, null Hubert Grand, null Helene Ferrand, null Christelle Raffaitin‐Cardin, null Hadjer Zellagui, null Celine Castang‐Brachet, null Frederique Boury, null Ana Alvarez Tena, null Isabelle Moura, null Pierre Kalfon, null Juliana Darasteanu, null Arnaud Monier, null Pascal Foucault, null Alexandra Depuille, null Stéphanie Laugier‐Robiolle, null Patrick Caneiro, null Maud Basso, null Etienne Larger, null Samir Bouam, null Wahiba Benzenati, null Leila Ait Bachir, null Camille Cussac Pillegand, null Marc Vasse, null Christophe Michard, null Nathanaëlle Montanier, null Luc Millot, null Françoise Crepet, null Danielle Ratsimba, null Kevin Bouiller, null Sophie Borot, null Isabelle Bruckert, null Annie Clergeot, null Franck Schillo, null Dorothée Vignes, null Muriel Bourgeon‐Ghittori, null Hamoud Lachgar, null Claire Lambert DE Cursay, null Stéphane Levante, null Jean Charles Auregan, null Antoine Merlet, null Cécile Zaragoza, null Gwénaëlle Arnault, null Anne‐Gaëlle Loupp, null Olivier Lesieur, null Mariam Roncato‐Saberan, null Didier Gouet, null Romain Lemarie, null Hong_an Allano, null Emmanuel Vivier, null Caroline Pariset, null Cédric Luyton, null Lucien Marchand, null Fanny Doroszewski, null Matthieu Pecquet, null Laurent Perard, null Sylvie Vuillermoz‐Blas, null Nicolas Kacki, null Patricia Charrier, null Amélie Ducet‐Boiffard, null Françoise Desroys Roure, null Olivier Bourron, null Dominique Bonnefont‐Rousselot, null Suzanne Laroche, null Franck Phan, null Agnès Hartemann, null Cyrielle Caussy, null Emmanuel Disse, null Claude Guerin, null Thomas Perpoint, null Philippe Moulin, null Régine Cartier, null Geoffroy Hariri, null Dorothée Chopin, null Camille Vatier, null Nathalie Bourcigaux, null Emmanuelle Chaigneau, null Sophie Christin‐Maitre, null Bruno Donadille, null Bruno Feve, null Sophie Lamothe, null Julie Sarfati, null Pascal Pernet, null Anne Chambon, null Delphine Demarsy, null Hugo Campagne, null Françoise Latil‐Plat, null Monica Berne, null Marilyne Grinand, null Marion Touzet, null Aydrey Zabulon, null Jocelyne Craspag, null Catherine Ledoux, null Cedric Contaret, null Blandine Janand‐Delenne, null Anaïs Giraud, null Marie Lou Lacrimini, null Joëlle Arrivie, null Deborah Ancelle, null Carine Guillois, null Bénédicte Fremy, null Amina Chaalal, null Gaëlle Barrande, null Anne Dorange, null Eglantine Rouanet, null Dominique Seret‐Begue, null Audrey Saoud, null Anne‐Marie Guedj, null Nathalie Bedos, null Fritz‐Line Velayoudom, null Marie Dumas, null Benoite Gonda, null Christine Coffin, null Stéphanie Gibiat, null Myriam Lungo, null Chantal Bully, null Pierre Serusclat, null Stella Bully, null Patricia Carre, null Jean‐Philippe Leberre, null Carlos Elkhoury, null Marine Thieux, null Laetitia Paradisi‐Prieur, and null CORONADO investigators

Subjects
Vaccination, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Diabetes mellitus, Medicine, business, medicine.disease
Published
2021

35. Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement

Author

Afef, Sfd, Anne Minello, Niasha Michot, Jean-Michel Petit, Bertrand Cariou, Armand Garioud, Maeva Guillaume, Jérôme Boursier, Laurent Castera, Claire Carette, Pierre Gourdy, Bruno Vergès, Fabrice Bonnet, Lawrence Serfaty, Dann Joseph Ouizeman, Rodolphe Anty, Hélène Fontaine, Cyrielle Caussy, Bruno Guerci, Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Hautepierre [Strasbourg], CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chercheur indépendant, Group Hospitalier public Sud Oise GHPSO (Creil), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, endocrine system diseases, Monitoring, Epidemiology, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Non-alcoholic Fatty Liver Disease, Diabetes mellitus, Diagnosis, Type 2 diabetes mellitus, Internal Medicine, medicine, Humans, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Fatty liver, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, General Medicine, medicine.disease, Comorbidity, Fibrosis, 3. Good health, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Liver function, Insulin Resistance, business, Pharmacological treatment
Abstract

International audience; Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.

Published
2021

36. Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

Author

Alexandra Montagner, Walter Wahli, Pierre Gourdy, Hervé Rémignon, Blandine Tramunt, Nguan Soon Tan, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie - Maladies Métaboliques - Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Fondation pour la Recherche Medicale (FRM) (DEA20170638343/FDM201906008682), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Nanyang Technological University [Singapour], Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), and LESUR, Hélène

Subjects
0301 basic medicine, medicine.medical_specialty, Very low-density lipoprotein, food.ingredient, medicine.drug_class, liver diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], G protein-coupled estrogen receptor, nuclear receptors, Context (language use), Review, Biochemistry, Microbiology, 03 medical and health sciences, Vitellogenin, 0302 clinical medicine, food, yolk, Internal medicine, Yolk, medicine, estrogen receptors, growth hormone, oogenesis, sexual dimorphism, vitellogenin, xenoestrogens, Molecular Biology, Fatty liver hemorrhagic syndrome, biology, medicine.disease, QR1-502, [SDV] Life Sciences [q-bio], 030104 developmental biology, Endocrinology, Estrogen, biology.protein, GPER, Vitellogenins, 030217 neurology & neurosurgery
Abstract

International audience; The liver is a vital organ that sustains multiple functions beneficial for the whole organism. It is sexually dimorphic, presenting sex-biased gene expression with implications for the phenotypic differences between males and females. Estrogens are involved in this sex dimorphism and their actions in the liver of several reptiles, fishes, amphibians, and birds are discussed. The liver participates in reproduction by producing vitellogenins (yolk proteins) and eggshell proteins under the control of estrogens that act via two types of receptors active either mainly in the cell nucleus (ESR) or the cell membrane (GPER1). Estrogens also control hepatic lipid and lipoprotein metabolisms, with a triglyceride carrier role for VLDL from the liver to the ovaries during oogenesis. Moreover, the activation of the vitellogenin genes is used as a robust biomarker for exposure to xenoestrogens. In the context of liver diseases, high plasma estrogen levels are observed in fatty liver hemorrhagic syndrome (FLHS) in chicken implicating estrogens in the disease progression. Fishes are also used to investigate liver diseases, including models generated by mutation and transgenesis. In conclusion, studies on the roles of estrogens in the non-mammalian oviparous vertebrate liver have contributed enormously to unveil hormone-dependent physiological and physiopathological processes.

Published
2021

37. Segregation of nuclear and membrane-initiated actions of estrogen receptor using genetically modified animals and pharmacological tools

Author

Jean-François Arnal, Marine Adlanmerini, Françoise Lenfant, Coralie Fontaine, and Pierre Gourdy

Subjects
Cell Nucleus, Canonical function, Cell Membrane, Estrogen Receptor alpha, Estrogen receptor, SUPERFAMILY, Non genomic signaling, Biology, Biochemistry, Genetically modified organism, Disease Models, Animal, Endocrinology, Nuclear receptor, Protein Domains, Mutation, Animals, Estrogen Receptor beta, Humans, Molecular Biology, Neuroscience, Estrogen receptor alpha, Signal Transduction
Abstract

Estrogen receptor alpha (ERα) and beta (ERβ) are members of the nuclear receptor superfamily, playing widespread functions in reproductive and non-reproductive tissues. Beside the canonical function of ERs as nuclear receptors, in this review, we summarize our current understanding of extra-nuclear, membrane-initiated functions of ERs with a specific focus on ERα. Over the last decade, in vivo evidence has accumulated to demonstrate the physiological relevance of this ERα membrane-initiated-signaling from mouse models to selective pharmacological tools. Finally, we discuss the perspectives and future challenges opened by the integration of extra-nuclear ERα signaling in physiology and pathology of estrogens.

Published
2021

38. 724-P: Factors Associated with Glycemic Control in People with Type 1 Diabetes (PWT1D) Switched to Once Daily (QD) Insulin Glargine (Gla) 300 U/mL (Gla-300): The European REALI Pooled Database

Author

Alice Ciocca, Gregory Bigot, Mireille Bonnemaire, Dirk Müller-Wieland, Corinne Jamoul, Riccardo C. Bonadonna, Nick Freemantle, Pierre Gourdy, and Didac Mauricio

Subjects
medicine.medical_specialty, Type 1 diabetes, Insulin glargine, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Internal Medicine, medicine, Once daily, medicine.disease, business, Glycemic, medicine.drug
Published
2021

39. 1017-P: Association between Death at Day 28 and Components of Microvascular Disease of with Diabetes Hospitalized for Coronavirus Disease-2019 (COVID-19): The CORONADO Study

Author

Laurence Kessler, Bertrand Cariou, Samy Hadjadj, Matthieu Wargny, Jean-Michel Halimi, Pierre-Jean Saulnier, Michel Marre, and Pierre Gourdy

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Diabetic kidney, business.industry, Endocrinology, Diabetes and Metabolism, Disease, Diabetic retinopathy, medicine.disease, Diabetic foot ulcer, Diabetes mellitus, Internal medicine, Hospital admission, Internal Medicine, medicine, In patient, business
Abstract

The prognostic role of microvascular complications (MVC) for all-cause death in patients with diabetes hospitalized for COVID-19 has been suggested. However, no detailed analysis of the microvascular burden is available so far. The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalized for COVID-19. The patients were enrolled after hospital admission from 03/10/2020 to 04/10/2020. MVC were defined as severe diabetic retinopathy (DR) and/or diabetic kidney disease (DKD, eGFR 300mg/g) and/or diabetic foot ulcer (DFU). We analysed the association of MVC with death within 28 days after admission. The status for all 3 MVC was ascertained for 1755 participants including 1048 (60%) free of MVC. Patients with MVC were older, had lower BMI, HbA1c, AST/ALT concentration, lymphocyte and platelet counts, while sex, type of diabetes and CRP were not significantly different. Patients with any MVC had a sex- and age-adjusted OR for death of 2.54 (95%CI: 1.94-3.31, P Disclosure P. Saulnier: None. S. Hadjadj: Advisory Panel; Self; Valbiotis, Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. L. Kessler: None. M. Marre: Board Member; Self; Merck Sharp & Dohme Corp., Consultant; Self; Novo Nordisk. J. Halimi: None. M. Wargny: None. P. Gourdy: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Research Support; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Sanofi. B. Cariou: Board Member; Self; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Research Support; Self; Amgen Inc., AstraZeneca, Regeneron Pharmaceuticals Inc., Speaker’s Bureau; Self; Abbott Diabetes, Akcea Therapeutics. For the coronado study group: n/a.

Published
2021

40. Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study

Author

L Bordier, Pierre Fontaine, Sandrine Lablanche, Abdallah Al-Salameh, Sarra Smati, Amandine Galioot, Adèle Lasbleiz, Olivier Bourron, Matthieu Wargny, Sandrine Coudol, Béatrice Guyomarch, Dominique Seret-Bégué, Sara Barraud, Eric Renard, Céline Gonfroy-Leymarie, Anna Flaus-Furmaniuk, Sybil Charrière, Bertrand Cariou, Emmanuel Cosson, Philippe Thuillier, Franck Mauvais-Jarvis, Jean-François Gautier, Bruno Vergès, Edith Bigot, Bruno Guerci, Bruno Fève, Matthieu Pichelin, Jean-Daniel Lalau, Louis Potier, Muriel Bourgeon, Samy Hadjadj, Gaëtan Prévost, Etienne Larger, Marion Munch, Nicolas Chevalier, Yves Reznik, Sophie Borot, Paul Sibilia, Pierre Gourdy, Bruno Laviolle, Coralie Amadou, Michel Marre, Blandine Tramunt, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Sud Francilien, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Jean Verdier [AP-HP], 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), CHU Saint-Antoine [AP-HP], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, CHU Bordeaux [Bordeaux], Centre Hospitalier René Dubos [Pontoise], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Grenoble, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance Publique - Hôpitaux de Marseille (APHM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Ambroise Paré [AP-HP], CHU Strasbourg, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Gonesse, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Diabétologie et Endocrinologie, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Tulane University, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], École pratique des hautes études (EPHE), CRHU Nancy, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, CH Evry-Corbeil, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), and CHU Toulouse [Toulouse]

Subjects
Male, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Severity of Illness Index, law.invention, 0302 clinical medicine, Endocrinology, Risk Factors, law, Hospital Mortality, Aged, 80 and over, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Sex Characteristics, COPD, Incidence, Incidence (epidemiology), General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Intensive care unit, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Intensive Care Units, Population study, Female, France, Sex characteristics, medicine.medical_specialty, Diabetes Complications, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Severity of illness, Diabetes Mellitus, medicine, Humans, Aged, Retrospective Studies, Inpatients, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, medicine.disease, Respiration, Artificial, business, 030217 neurology & neurosurgery
Abstract

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

Published
2021

41. Efficacy and Safety of Switching Patients Inadequately Controlled on Basal Insulin to Insulin Glargine 300 U/mL: The TRANSITION 2 Study

Author

D. Gouet, Zahra Boultif, Pierre Gourdy, Bruno Guerci, and Amar Bahloul

Subjects
medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Hypoglycemia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Insulin, Glargine, Prospective cohort study, Gla-300, Original Research, Real-world evidence, Insulin glargine, business.industry, Basal insulin, nutritional and metabolic diseases, Real-life, medicine.disease, business, medicine.drug
Abstract

Introduction This study aimed to determine, in close to real-life conditions, the efficacy and safety of switching from any basal insulin to insulin glargine 300 U/mL (Gla-300) in patients with uncontrolled type 2 diabetes (T2D). Methods This was an interventional, multicenter, single-arm, prospective study with a 24-week treatment phase. Adult patients with T2D treated with basal insulin with or without other antidiabetics, HbA1c > 7.5%, and fasting self-monitored blood glucose (F-SMBG) > 130 mg/dL (mean of three measures) at baseline were included. Insulin dose was titrated to reach F-SMBG 90–130 mg/dL. Efficacy and safety were assessed at 12 weeks (W12) and 24 weeks (W24). The main outcome parameter was HbA1c change between baseline and W24. Safety parameters included self-reported hypoglycemia (any type). Patients’ satisfaction with the treatment was assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Results A total of 140 patients were included and 137 were treated. Mean HbA1c decreased from 8.64% at baseline to 8.14% at W12 (mean difference [95% CI] − 0.51% [− 0.64; − 0.38]) and 8.01% at W24 (− 0.64% [− 0.81; − 0.46]). Target F-SMBG was reached in 35.0% of the patients at W12 and 38.4% at W24. The percentages of patients reaching HbA1c levels

Published
2019

42. Direct comparison of the specialised blood fibrosis tests FibroMeterV2G and Enhanced Liver Fibrosis score in patients with non-alcoholic fatty liver disease from tertiary care centres

Author

Adrien Lannes, Floraine Zuberbuhler, Sophie Michalak, Pierre Gourdy, Isabelle Fouchard-Hubert, Janick Selves, Maeva Guillaume, S. Metivier, Jean-Marie Peron, Jérôme Boursier, Christophe Bureau, Marie-Angèle Robic, Frédéric Oberti, Cyrielle Delabaudière, Valérie Moal, and Paul Calès

Subjects
medicine.medical_specialty, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Fatty liver, Gastroenterology, Disease, medicine.disease, Tertiary care, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, Liver biopsy, Clinical endpoint, medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), In patient, 030212 general & internal medicine, business
Abstract

BACKGROUND The Enhanced Liver Fibrosis score (ELF) and the FibroMeterV2G are two specialized blood fibrosis tests which include direct markers of liver fibrosis. They have been shown to be more accurate than the simple blood fibrosis tests FIB4 and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). AIMS To directly compare the accuracies of ELF and FibroMeterV2G for the non-invasive diagnosis of liver fibrosis in NAFLD. METHODS Four hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeterV2G , NFS, and FIB4. Advanced fibrosis F3/4 on liver biopsy (NASH CRN scoring) was the primary endpoint. RESULTS Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeterV2G (0.804 ± 0.021) had significantly higher AUROC than NFS (0.722 ± 0.025, P

Published
2019

43. Gestational diabetes and acromegaly: Single‐centre experience of 14 pregnancies

Author

Philippe Caron, Delphine Vezzosi, Antoine Bennet, Pierre Gourdy, C. Mouly, Solange Grunenwald, and M. Vialon

Subjects
Adult, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pregnancy, Internal medicine, Diabetes mellitus, Acromegaly, medicine, Humans, Insulin-Like Growth Factor I, Family history, Human Growth Hormone, business.industry, Obstetrics, medicine.disease, Gestational diabetes, Diabetes, Gestational, Single centre, 030220 oncology & carcinogenesis, Gestation, Female, Somatostatin, business
Abstract

Introduction The prevalence of gestational diabetes (GD) in women with acromegaly is rarely reported. The aims of this study were to evaluate the prevalence of GD in acromegalic women submitted to a systematic screening for GD and then to compare women with or without GD. Patients and methods We studied 14 pregnancies in 11 women (34.0 ± 3.6 years) treated with somatostatin analogues after a pituitary surgery (n = 6) or as primary (n = 5) therapy, and treatment was discontinued at the time of pregnancy diagnosis for 13 pregnancies. One woman was diagnosed with acromegaly during pregnancy and was treated with octreotide LAR between 12 and 18 weeks of gestation. Before pregnancy, no women had diabetes mellitus, and GH/IGF-1 hypersecretion was uncontrolled in 6 women. Results Gestational diabetes was diagnosed during 7 pregnancies (50%) in 6 women (one woman had GD during her 2 pregnancies), according to fasting blood glucose (n = 5) or to an oral glucose tolerance test (n = 2). Before pregnancy, IGF-1 was not controlled in 4 GD+ and in 2 GD- women. Women with GD were not significantly older and had increased pregestational BMI (P = .02), with a more frequent family history of type 2 diabetes, no personal history of GD but of macrosomia for one patient. Conclusion The prevalence of GD in our women is higher than that reported in the literature, probably resulting from the systematic GD screening and to the age of women. Therefore, routine screening of GD should be considered in women with acromegaly, particularly in those with risk factors for GD and with uncontrolled IGF-1 levels before pregnancy.

Published
2019

44. Prise de position de la Société Francophone du Diabète (SFD) : évaluation du rapport bénéfices-risques des inhibiteurs de SGLT2

Author

A. Grimaldi, Bernard Charbonnel, André Scheen, Alfred Penfornis, Jean-Pierre Riveline, Bruno Detournay, Lyse Bordier, Emmanuel Cosson, Hélène Hanaire, Bernard Bauduceau, Patrice Darmon, Pierre Fontaine, Gérard Chabrier, Jacques Bringer, Bruno Guerci, and Pierre Gourdy

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published
2019

45. ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity

Author

Anne Fougerat, Gabriele Schoiswohl, Arnaud Polizzi, Marion Régnier, Carina Wagner, Sarra Smati, Tiffany Fougeray, Yannick Lippi, Frederic Lasserre, Ilyès Raho, Valentine Melin, Blandine Tramunt, Raphaël Métivier, Caroline Sommer, Fadila Benhamed, Chantal Alkhoury, Franziska Greulich, Céline Jouffe, Anthony Emile, Michael Schupp, Pierre Gourdy, Patricia Dubot, Thierry Levade, Delphine Meynard, Sandrine Ellero-Simatos, Laurence Gamet-Payrastre, Ganna Panasyuk, Henriette Uhlenhaut, Ez-Zoubir Amri, Céline Cruciani-Guglielmacci, Catherine Postic, Walter Wahli, Nicolas Loiseau, Alexandra Montagner, Dominique Langin, Achim Lass, Hervé Guillou, Graz University of Technology [Graz] (TU Graz), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), 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 Paris Cité (UPC), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Nanyang Technological University [Singapour], University of Lausanne (UNIL), BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität [Graz, Autriche]-Medical University Graz, Région Occitanie, FRM (FDM201906008682), Boulos Foundation, ERC-2018-COG-MetaboSENS-819543, German Research Foundation (DFG) (SCH 2546/5-1), the Leuchtturmprojekt/Flagship Project 'Lipases and Lipid Signaling' funded by BioTechMed-Graz, ANR-16-CE14-0029,NUTRISENSPIK,Déterminants moléculaires de l'homéostasie hépatique nutritive(2016), ANR-17-CE14-0015,HepAdialogue,Impact du métabolisme des acides gras des tissus adipeux et du foie sur l'insulinorésistance(2017), ANR-21-CE14-0079,Hepatologic,Réseau de controle des réponses transcriptionnelles hépatiques aux challenges nutritionnels par des récepteurs nucléaires(2021), European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Medical University of Graz, Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Helmholtz Zentrum München = German Research Center for Environmental Health, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lee Kong Chian School of Medicine, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Technische Universität Graz (TU Graz), Région Occitanie B.T. was supported by FRM (FDM201906008682)., Boulos Foundation and FRM., German Research Foundation (DFG) (SCH 2546/5-1 to M.S.), I3535, andP34899 (A.L.) by Austrian Science Fund (FWF, ERC-2018-COG-MetaboSENS- 819543 (G.P.), the Leuchtturmprojekt/Flagship Project ‘‘Lipases and Lipid Signaling’’ (A.L.), funded by BioTechMed-Graz, and by P28882-B21 (G.S.), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, LESUR, Hélène, Impact du métabolisme des acides gras des tissus adipeux et du foie sur l'insulinorésistance - - HepAdialogue2017 - ANR-17-CE14-0015 - AAPG2017 - VALID, Réseau de controle des réponses transcriptionnelles hépatiques aux challenges nutritionnels par des récepteurs nucléaires - - Hepatologic2021 - ANR-21-CE14-0079 - AAPG2021 - VALID, Déterminants moléculaires de l'homéostasie hépatique nutritive - - NUTRISENSPIK2016 - ANR-16-CE14-0029 - AAPG2016 - VALID, and AgreenSkills+ - AGREENSKILLSPLUS - - EC:FP7:PEOPLE2014-05-05 - 2019-05-04 - 609398 - VALID

Subjects
fasting, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Adipose Tissue, White, Metabolism, Fgf21, Pparα, Fasting, Ketogenesis, Lipolysis [Atgl, Cp], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Ketone Bodies, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, PPARα, General Biochemistry, Genetics and Molecular Biology, ATGL, FGF21, Adipose Tissue, Brown, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], PPAR alpha, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, CP: Metabolism, ketogenesis, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Adipose Tissue, Hepatocytes, lipolysis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β3-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.

Published
2022

46. Sugar Addictive Behavior Resulting From Hypoglycemia Provoked by Insulin Misuse

Author

Laurent Schmitt, Charlotte Rougier, Yann Hakimi, Hélène Hanaire, Pauline Hadjadj, Camille Ponté, Juliette Salles, and Pierre Gourdy

Subjects
Blood Glucose, business.industry, Insulin, medicine.medical_treatment, MEDLINE, General Medicine, Hypoglycemia, medicine.disease, Bioinformatics, Behavior, Addictive, medicine, Humans, Sugar, Addictive behavior, business, Sugars
Published
2021

47. Association Between the ACE Insertion/Deletion Polymorphism and Risk of Lower-Limb Amputation in Patients With Long-Standing Type 1 Diabetes

Author

Pierre Gourdy, Ninon Foussard, Michel Marre, Jean-François Gautier, Kamel Mohammedi, Charlyne Carpentier, François Alhenc-Gelas, André Scheen, Samy Hadjadj, Séverine Dubois, Bernard Bauduceau, Ronan Roussel, Gilberto Velho, Vincent Rigalleau, Yawa Abouleka, Guillaume Charpentier, and Louis Potier

Subjects
Adult, Male, medicine.medical_specialty, Genotype, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Peptidyl-Dipeptidase A, Gastroenterology, Amputation, Surgical, Polymorphism (computer science), Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Prospective Studies, Advanced and Specialized Nursing, Type 1 diabetes, Polymorphism, Genetic, Proportional hazards model, business.industry, Hazard ratio, Odds ratio, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, Amputation, Lower Extremity, business
Abstract

OBJECTIVE The ACE insertion/deletion (I/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes. RESEARCH DESIGN AND METHODS ACE I/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders. RESULTS Among 1,301 participants (male 54%, age 41 ± 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95 %CI 1.03–4.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16–13.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33–4.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers. CONCLUSIONS This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.

Published
2021

48. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target

Author

Françoise Lenfant, Anne Fougerat, Cheng Zhang, Laurence Gamet-Payrastre, Marion Régnier, Maeva Guillaume, Lorraine Smith, Thierry Levade, Arnaud Polizzi, Yannick Lippi, Caroline Sommer, Marine Huillet, Talal Al Saati, Hervé Guillou, Sandrine Lagarrigue, Sarra Smati, Nicolas Loiseau, Jinghong Wan, Catherine Postic, Yuna Blum, Alain Marrot, Adil Mardinoglu, Tiffany Fougeray, Muhammad Arif, Walter Wahli, Blandine Tramunt, Christophe Bureau, Patricia Dubot, Pierre Gourdy, Sandrine Ellero-Simatos, Céline Lukowicz, Alexandra Montagner, Frédéric Lasserre, Rémy Burcelin, Aurélie Batut, Claire Naylies, Jean-François Arnal, Alexia Laroyenne, Nathalie Hennuyer, Sophie Lotersztajn, Justine Bertrand-Michel, Bart Staels, Jean-Philippe Pradère, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Royal Institute of Technology [Stockholm] (KTH ), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lab Excellence Inflamex (CRI INSERM U1149 - Bichat Medical Faculty), Université Paris Diderot - Paris 7 (UPD7), Plateforme Ezop (Ezop), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), 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), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], Université de Lausanne (UNIL), CHU Toulouse [Toulouse], ANR-20-CE14-0035-04, Agence Nationale de la Recherche, FATMAL, Joint Programming Initiative A healthy diet for a healthy life, N/A, Institut National de la Santé et de la Recherche Médicale, N/A, Société Française de Nutrition, N/A, Société Francophone du Diabète, N/A, Société Nationale Française de Gastro-Entérologie, N/A, Association Française pour l'Etude du Foie, N/A, Région Occitanie, N/A, Agreenskills, ANR-17-CE14-0035,PUSHUPS,Etude de la dysfonction des cellules souches musculaires au cours du sepsis(2017), LESUR, Hélène, Etude de la dysfonction des cellules souches musculaires au cours du sepsis - - PUSHUPS2017 - ANR-17-CE14-0035 - AAPG2017 - VALID, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ligue Nationale Contre le Cancer (LNCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Université de Lausanne = University of Lausanne (UNIL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Nanyang Technological University (NTU), Hôpital de Rangueil, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)

Subjects
Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Peroxisome proliferator-activated receptor, Biology, Diet, High-Fat, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Fibrosis, Internal medicine, lipid metabolism, medicine, Metabolome, Animals, Humans, PPAR alpha, nonalcoholic steatohepatitis, liver metabolism, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Fatty liver, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipid metabolism, Lipidome, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Gene expression profiling, Disease Models, Animal, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Liver, chemistry, gene expression, Female, 030211 gastroenterology & hepatology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

ObjectiveWe evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.DesignDifferent models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.ResultsThe different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.ConclusionsThese findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.Trial registration numberNCT02390232.

Published
2021

49. ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes

Author

Séverine Dubois, André Scheen, Charlyne Carpentier, Samy Hadjadj, François Alhenc-Gelas, Pierre Gourdy, Ronan Roussel, Michel Marre, Yawa Abouleka, Jean-François Gautier, Gilberto Velho, and Kamel Mohammedi

Subjects
Advanced and Specialized Nursing, Type 1 diabetes, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Hazard ratio, Renal function, 030209 endocrinology & metabolism, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Diabetes mellitus, Internal Medicine, Albuminuria, Medicine, 030212 general & internal medicine, medicine.symptom, Risk factor, business, Pathophysiology/Complications, Kidney disease
Abstract

OBJECTIVE The deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 1,155 participants from three French and Belgian cohorts were monitored for a median duration of 14 (interquartile range 13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in the estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than –3 mL/min/1.73 m2 per year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HRs) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested. RESULTS Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95% CI 1.32–3.40; P = 0.001). Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with an increased risk of the primary outcome. The ACE genotype enhanced net reclassification improvement (0.154, 95% CI 0.007–0.279; P = 0.04) and integrated discrimination improvement (0.012, 95%CI 0.001–0.021; P = 0.02) for primary outcome stratification. CONCLUSIONS The D-allele of the ACE I/D polymorphism was associated with an increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.

Published
2021

50. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

Author

Nicolas Chevalier, Bruno Vergès, Etienne Larger, L Bordier, Delphine Demarsy, Jean-François Thébaut, Dominique Seret-Bégué, Matthieu Wargny, Pierre-Antoine Gourraud, Coralie Amadou, Nathanaëlle Montanier, Myriam Lungo, P. Serusclat, Claude Chaumeil, Audrey Zabulon, Louis Potier, Jean-Baptiste Bonnet, Bertrand Cariou, Matthieu Pichelin, Pierre Gourdy, Anne-Marie Guedj, Nathalie Jeandidier, Jean-Philippe Le Berre, René Robert, Vincent Rigalleau, Ronan Roussel, O. Dupuy, Fritz-Line Velayoudom, Sarra Smati, Jean-François Gautier, Françoise Plat, Samy Hadjadj, Olivier Bourron, Camille Vatier, Patrice Winiszewski, Pierre-Yves Benhamou, Blandine Tramunt, Marie Dumas, Philippe Moulin, Patrice Darmon, Anna Flaus-Furmaniuk, B. Delenne, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie - Maladies Métaboliques - Nutrition, CHU Toulouse [Toulouse], Centre Hospitalier Sud Francilien, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CH Evry-Corbeil, 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 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), Unité de recherche de l'institut du thorax (ITX-lab), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Percentile, Home discharge, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030204 cardiovascular system & hematology, 0302 clinical medicine, Mechanical ventilation, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Hospital Mortality, Aged, 80 and over, Anticoagulant, Diabetes, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Patient Discharge, 3. Good health, Metformin, Hospitalization, Death, Female, France, Admission plasma glucose, medicine.drug, medicine.medical_specialty, Statin, HbA1c, Coronavirus disease 2019 (COVID-19), medicine.drug_class, 030209 endocrinology & metabolism, Article, Diabetes Complications, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Diabetes Mellitus, Humans, HbA(1c), Aged, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, Length of Stay, medicine.disease, Respiration, Artificial, Discharge, business, Follow-Up Studies
Abstract

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

Published
2021

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