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Kim K B Clemmensen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Jonas S Quist Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Dorte Vistisen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Daniel R Witte Department of Public Health, Aarhus University, Aarhus, Denmark
Danish Diabetes Academy, Odense, Denmark

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Anna Jonsson NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Oluf Pedersen NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Torben Hansen NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Jens J Holst NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Torsten Lauritzen Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark

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Marit E Jørgensen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark

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Signe Torekov NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Kristine Færch Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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). Additionally, the time of the day of an OGTT seems to influence the glucose response with higher post-load blood glucose levels in the afternoon and evening compared to the morning ( 1 , 3 ). The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose

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Gaëtan Prévost Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France
Department of Endocrinology, Diabetes and Metabolic Diseases, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France

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Marie Picot Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Marie-Anne Le Solliec Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Arnaud Arabo Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Hind Berrahmoune Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France
Department of Endocrinology, Diabetes and Metabolic Diseases, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France

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Mouna El Mehdi Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Saloua Cherifi Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Alexandre Benani Center for Taste and Feeding Behaviour, CNRS (UMR6265), INRA (UMR1324), Université de Bourgogne-Franche Comté, Dijon , France

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Emmanuelle Nédélec Center for Taste and Feeding Behaviour, CNRS (UMR6265), INRA (UMR1324), Université de Bourgogne-Franche Comté, Dijon , France

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Françoise Gobet Department of Anatomopathophysiology, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France

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Valéry Brunel Department of Biochemistry, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France

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Jérôme Leprince Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Hervé Lefebvre Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France
Department of Endocrinology, Diabetes and Metabolic Diseases, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France

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Youssef Anouar Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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Nicolas Chartrel Normandie Univ, UNIROUEN, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (DC2N), Rouen, France

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that this neuropeptide regulates glycemia by acting as an incretin ( 24 ). In humans, an association between the 26RFa/GPR103 system and the regulation of glucose homeostasis is far more limited. This observation prompted us to investigate in detail

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Lili Liu Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhuo Shao Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, Shanghai, China

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Ying Xia Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Jiabi Qin Department of Epidemiology & Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

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Yang Xiao Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhiguang Zhou Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zubing Mei Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

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. Incretin-based drugs, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may offer an opportunity to avoid these side effects. Theoretically, GLP-1 RAs are structurally and functionally similar to

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David S Mathiesen Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Jonatan I Bagger Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Katrine B Hansen Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark

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Anders E Junker Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Astrid Plamboeck Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Signe Harring Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark

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Thomas Idorn Center for Cancer and Organ Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Mads Hornum Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Cancer and Organ Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Jens J Holst Novartis Healthcare A/S, Copenhagen, Denmark

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Anna E Jonsson Novartis Healthcare A/S, Copenhagen, Denmark

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Torben Hansen Novartis Healthcare A/S, Copenhagen, Denmark

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Tina Vilsbøll Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Novartis Healthcare A/S, Copenhagen, Denmark
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Asger Lund Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Novartis Healthcare A/S, Copenhagen, Denmark
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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chronic hyperglucagonemia and a severely reduced incretin effect ( 3 , 4 , 5 ). The incretin effect refers to the greater insulin response during oral glucose ingestion compared to isoglycemic intravenous (IV) glucose infusion (IIGI) ( 5 ). The incretin

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Jukka Koffert Department of Gastroenterology, Turunmaa Hospital, Turku, Finland
Turku PET Centre, University of Turku, Turku, Finland

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Henri Honka Turku PET Centre, University of Turku, Turku, Finland

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Jarmo Teuho Department of Gastroenterology, Turunmaa Hospital, Turku, Finland

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Saila Kauhanen Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland

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Saija Hurme Institute of Biostatistics, University of Turku, Turku, Finland

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Riitta Parkkola Turku PET Centre, University of Turku, Turku, Finland
Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland

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Vesa Oikonen Turku PET Centre, University of Turku, Turku, Finland

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Andrea Mari Institute of Neuroscience, National Research Council, Padua, Italy

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Andreas Lindqvist Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Nils Wierup Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Leif Groop Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Pirjo Nuutila Turku PET Centre, University of Turku, Turku, Finland
Department of Endocrinology, Turku University Hospital, Turku, Finland

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several potential vasoactive substances increase ( 8 ). In rodents, experimental hyperglycemia increases and hypoglycemia decreases pancreatic islet perfusion ( 9 ). Moreover, incretins have been shown to regulate BF in the splanchnic and systemic

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David P Sonne Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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Asger Lund Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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Jens Faber Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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Jens J Holst Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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Tina Vilsbøll Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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Filip K Knop Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark

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during both oral and i.v. glucose and thereby contribute to the observed TSH suppression patterns (11) . Also, as GIP and GLP1 increase somatostatin secretion, at least in animals (34) , suppression of TSH during incretin infusion might have been

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Henri Honka Turku PET Centre, University of Turku, Turku, Finland

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Jukka Koffert Turku PET Centre, University of Turku, Turku, Finland
Department of Gastroenterology, Turku University Hospital, Turku, Finland

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Saila Kauhanen Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland

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Nobuyuki Kudomi Faculty of Medicine, Kagawa University, Kagawa, Japan

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Saija Hurme Department of Biostatistics, University of Turku, Turku, Finland

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Andrea Mari Institute of Neuroscience, National Research Council, Padua, Italy

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Andreas Lindqvist Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Nils Wierup Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Riitta Parkkola Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland

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Leif Groop Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden

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Pirjo Nuutila Turku PET Centre, University of Turku, Turku, Finland
Department of Endocrinology, Turku University Hospital, Turku, Finland

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incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) account for the gut-derived amplification of insulin secretion ( 4 ). In addition to the effect on pancreatic islets, we ( 5 ) and others ( 6 ) have

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Cheryl M Isherwood Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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M Denise Robertson Section of Metabolic Medicine, Food and Macronutrients, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Debra J Skene Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Jonathan D Johnston Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Obesity is a major cause of type 2 diabetes. Transition from obesity to type 2 diabetes manifests in the dysregulation of hormones controlling glucose homeostasis and inflammation. As metabolism is a dynamic process that changes across 24 h, we assessed diurnal rhythmicity in a panel of 10 diabetes-related hormones. Plasma hormones were analysed every 2 h over 24 h in a controlled laboratory study with hourly isocaloric drinks during wake. To separate effects of body mass from type 2 diabetes, we recruited three groups of middle-aged men: an overweight (OW) group with type 2 diabetes and two control groups (lean and OW). Average daily concentrations of glucose, triacylglycerol and all the hormones except visfatin were significantly higher in the OW group compared to the lean group (P < 0.001). In type 2 diabetes, glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 increased further (P < 0.05), whereas triacylglycerol, ghrelin and plasminogen activator inhibitor-1 concentrations were significantly lower compared to the OW group (P < 0.001). Insulin, C-peptide, glucose-dependent insulinotropic peptide and leptin exhibited significant diurnal rhythms in all study groups (P < 0.05). Other hormones were only rhythmic in 1 or 2 groups. In every group, hormones associated with glucose regulation (insulin, C-peptide, glucose-dependent insulinotropic peptide, ghrelin and plasminogen activator inhibitor-1), triacylglycerol and glucose peaked in the afternoon, whereas glucagon and hormones associated with appetite and inflammation peaked at night. Thus being OW with or without type 2 diabetes significantly affected hormone concentrations but did not affect the timing of the hormonal rhythms.

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Kim K B Clemmensen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Jonas S Quist Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Dorte Vistisen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Daniel R Witte Department of Public Health, Aarhus University, Aarhus, Denmark
Danish Diabetes Academy, Odense, Denmark

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Anna Jonsson NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Oluf Pedersen NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Torben Hansen NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

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Jens J Holst NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Torsten Lauritzen Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark

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Marit E Jørgensen Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark

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Signe Torekov NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Kristine Færch Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Agnieszka Kosowska Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Enrique Gallego-Colon Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Wojciech Garczorz Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Agnieszka Kłych-Ratuszny Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Mohammad Reza F Aghdam Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Michał Woz´niak Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Andrzej Witek Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Agnieszka Wróblewska-Czech Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Anna Cygal Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Jerzy Wojnar Department of Internal Medicine and Oncological Chemotherapy, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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Tomasz Francuz Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland

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( 4 ). Alternatively, incretin mimetic drugs are a relatively new group of drugs used in the treatment of diabetes that are currently recommended by American Diabetes Association in dual therapy with metformin for the treatment of T2D ( 5 , 6 ). The

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