title: Nonsuppressed Glucagon After Glucose Challenge as a Potential Predictor for Glucose Tolerance.
abstract: Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT). Glucagon levels were measured during OGTT in a total of 4,194 individuals without diabetes in three large European cohorts. Longitudinal changes in glucagon suppression were investigated in 50 participants undergoing a lifestyle intervention. Only 66-79% of participants showed suppression of glucagon at 120 min (fold change glucagon120/0<1) during OGTT, whereas 21-34% presented with increasing glucagon levels (fold change glucagon120/0≥1). Participants with nonsuppressed glucagon120had a lower risk of IGT in all cohorts (odds ratio 0.44-0.53,P< 0.01). They were also leaner and more insulin sensitive and had lower liver fat contents. In the longitudinal study, an increase of fold change glucagon120/0was associated with an improvement in insulin sensitivity (P= 0.003). We characterize nonsuppressed glucagon120during the OGTT. Lower glucagon suppression after oral glucose administration is associated with a metabolically healthier phenotype, suggesting that it is not an adverse phenomenon.
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Róbert
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Diabetes and Obesity Research Program, Research Programs Unit, Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland.
authors.forename: Liisa H
authors.initials: LH
authors.lastname: Hakaste
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Ahlqvist
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.affiliation: Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.|Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.affiliation: Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.affiliation: Université Côte d'Azur, CHU, INSERM, CNRS, Institute of Research on Cancer and Aging in Nice (IRCAN), Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.
authors.forename: Baptist
authors.initials: B
authors.lastname: Gallwitz
authors.affiliation: Diabetes and Obesity Research Program, Research Programs Unit, Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland.|Department of Endocrinology, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.|Finnish Institute of Molecular Medicine, Helsinki University, Helsinki, Finland.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany andreas.fritsche@med.uni-tuebingen.de.|Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich, University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control; D004035:Diet Therapy; D015444:Exercise; D005260:Female; D005387:Finland / Q000453:epidemiology; D005934:Glucagon / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism* / Q000628:therapy; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D005934:Glucagon