Differential contribution of alpha and beta cell dysfunction to impaired fasting glucose and impaired glucose tolerance

Jacob D. Kohlenberg, Marcello C. Laurenti, Aoife M. Egan, Daniel Schembri Wismayer, Kent R. Bailey, Claudio Cobelli, Chiara Dalla Man, Adrian Vella

Research output: Contribution to journalArticlepeer-review


Aims/hypothesis: People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG. Methods: We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose. We studied 39 non-diabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m2), categorised by fasting glucose and glucose tolerance status. After an overnight fast, a variable insulin infusion was used to maintain glucose at ~4.44 mmol/l (07:00 to 08:30 hours). At 09:00 hours, graded glucose infusion commenced at 1 mg kg−1 min−1 and doubled every 60 min until 13:00 hours. GSR and ISR were calculated by nonparametric deconvolution from concentrations of glucagon and C-peptide, respectively. Results: The relationship of ISR with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that in people with normal fasting glucose and normal glucose tolerance. GSR exhibited a single-exponential relationship with glucose that could be characterised by G50, the change in glucose necessary to suppress GSR by 50%. G50 was increased in IFG compared with normal fasting glucose regardless of the presence of impaired or normal glucose tolerance. Conclusions/interpretation: These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)201-212
Number of pages12
Issue number1
StatePublished - Jan 2023


  • Alpha cell function
  • Beta cell function
  • Deconvolution
  • Glucagon suppression
  • Impaired fasting glucose
  • Impaired insulin action
  • Insulin secretion
  • Prediabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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