Fasting glucagon concentrations are associated with longitudinal decline of β-cell function in non-diabetic humans

Jon D. Adams, Chiara Dalla Man, Marcello C. Laurenti, M. Daniela Hurtado Andrade, Claudio Cobelli, Robert A. Rizza, Kent R. Bailey, Adrian Vella

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Purpose: Abnormal glucagon concentrations are a feature of prediabetes but it is uncertain if α-cell dysfunction contributes to a longitudinal decline in β-cell function. We therefore sought to determine if a decline in β-cell function is associated with a higher nadir glucagon in the postprandial period or with higher fasting glucagon. Methods: This was a longitudinal study in which 73 non-diabetic subjects were studied on 2 occasions 6.6 ± 0.3 years apart using a 2-hour, 7-sample oral glucose tolerance test. Disposition Index (DI) was calculated using the oral minimal model applied to the measurements of glucose, insulin, C-peptide concentrations during the studies. We subsequently examined the relationship of glucagon concentrations at baseline with change in DI (used as a measure of β-cell function) after adjusting for changes in weight and the baseline value of DI. Results: After adjusting for covariates, nadir postprandial glucagon concentrations were not associated with changes in β-cell function as quantified by DI. On the other hand, fasting glucagon concentrations during the baseline study were inversely correlated with longitudinal changes in DI. Conclusions: Defects in α-cell function, manifest as elevated fasting glucagon, are associated with a subsequent decline in β-cell function. It remains to be ascertained if abnormal α-cell function contributes directly to loss of β-cell secretory capacity in the pathogenesis of type 2 diabetes.

Original languageEnglish (US)
Article number154175
JournalMetabolism: Clinical and Experimental
StatePublished - Apr 2020


  • Glucagon
  • Insulin action
  • Prediabetes
  • α-Cell function
  • β-Cell function

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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