Insulin resistance is accompanied by increased fasting glucagon and delayed glucagon suppression in individuals with normal and impaired glucose regulation

Research output: Contribution to journalArticle


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.


  • Kristine Færch
  • Dorte Vistisen
  • Giovanni Pacini
  • Signe S. Torekov
  • Nanna B. Johansen
  • Daniel R. Witte
  • Anna Jonsson
  • Oluf Pedersen
  • Torben Hansen
  • Torsten Lauritzen
  • Marit E. Jørgensen
  • Bo Ahrén
  • Jens Juul Holst
External organisations
  • Steno Diabetes Center Copenhagen
  • University of Copenhagen
  • Aarhus University
  • CNR Institute of Neuroscience, Pisa
  • Danish Diabetes Academy
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)3473-3481
Number of pages9
Issue number11
Publication statusPublished - 2016 Nov 1
Publication categoryResearch