Loss of beta cell function as fasting glucose increases in the non-diabetic range

Diabetologia. 2004 Jul;47(7):1157-1166. doi: 10.1007/s00125-004-1454-z. Epub 2004 Jul 13.


Aims/hypothesis: Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline.

Methods: Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis.

Results: As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG.

Conclusions/interpretation: The range of FPG over which progressive loss of the first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase insulin responses declining at FPG concentrations above 6.0 mmol/l.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Blood Pressure
  • Body Mass Index
  • C-Peptide / blood
  • Cohort Studies
  • Fasting
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Male
  • Models, Biological
  • Reference Values
  • Risk Factors
  • Smoking


  • Blood Glucose
  • C-Peptide
  • Insulin