Nonsuppressed glucagon after glucose challenge as a potential predictor for glucose tolerance

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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 glucagon120 had 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 glucagon120/0 was associated with an improvement in insulin sensitivity (P = 0.003). We characterize nonsuppressed glucagon120 during the OGTT. Lower glucagon suppression after oral glucose administration is associated with a metabolically healthier phenotype, suggesting that it is not an adverse phenomenon.


  • Róbert Wagner
  • Liisa H. Hakaste
  • Emma Ahlqvist
  • Martin Heni
  • Jürgen Machann
  • Fritz Schick
  • Emmanuel Van Obberghen
  • Norbert Stefan
  • Baptist Gallwitz
  • Tiinamaija Tuomi
  • Hans Ulrich Häring
  • Leif Groop
  • Andreas Fritsche
External organisations
  • University of Tübingen
  • Skåne University Hospital
  • University of Côte d'Azur
  • University of Helsinki
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
Issue number5
Publication statusPublished - 2017 May 1
Publication categoryResearch