title: Insulin Resistance Is Accompanied by Increased Fasting Glucagon and Delayed Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation.
abstract: Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon suppression was defined as suppression in the period from 0 to 30 min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin sensitivity was estimated by the validated insulin sensitivity index. Individuals with screen-detected diabetes had 30% higher fasting glucagon levels and diminished early glucagon suppression, but greater late glucagon suppression when compared with individuals with normal glucose tolerance (P ≤ 0.014). Higher insulin resistance was associated with higher fasting glucagon levels, less early glucagon suppression, and greater late glucagon suppression (P < 0.001). The relationship between insulin sensitivity and fasting glucagon concentrations was nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and delayed glucagon suppression, together with increased circulating insulin levels, develop in parallel with insulin resistance. Therefore, glucose maintenance during insulin resistance may depend not only on hyperinsulinemia but also on the ability to suppress glucagon early after glucose intake.
authors: Steno Diabetes Center, Gentofte, Denmark krif@steno.dk.
authors: Kristine
authors: K
authors: Færch
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Dorte
authors: D
authors: Vistisen
authors: Metabolic Unit, Institute of Neurosciences, Istituto Di Neuroscienze-Consiglio Nazionale Delle Ricerche, Padova, Italy.
authors: Giovanni
authors: G
authors: Pacini
authors: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Signe S
authors: SS
authors: Torekov
authors: Steno Diabetes Center, Gentofte, Denmark.|The Danish Diabetes Academy, Odense, Denmark.
authors: Nanna B
authors: NB
authors: Johansen
authors: The Danish Diabetes Academy, Odense, Denmark.|Section of General Practice, Institute of Public Health, University of Aarhus, Aarhus, Denmark.
authors: Daniel R
authors: DR
authors: Witte
authors: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Anna
authors: A
authors: Jonsson
authors: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Oluf
authors: O
authors: Pedersen
authors: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Torben
authors: T
authors: Hansen
authors: Section of General Practice, Institute of Public Health, University of Aarhus, Aarhus, Denmark.
authors: Torsten
authors: T
authors: Lauritzen
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Marit E
authors: ME
authors: Jørgensen
authors: Division of Medicine, Lund University, Lund, Sweden.
authors: Bo
authors: B
authors: Ahrén
authors: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Jens Juul
authors: JJ
authors: Holst
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose