Loss of beta cell function as fasting glucose increases in the non-diabetic range.
OBJECTIVE
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
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.
Godsland
I F
IF
Department of Endocrinology and Metabolic Medicine, Division of Medicine, Faculty of Medicine, Imperial College London, St. Mary's Hospital, Mint Wing 2nd Floor, London, W2 1PG, UK. i.godsland@imperial.ac.uk.|Wynn Institute, Division of Medicine, Imperial College London, London, UK. i.godsland@imperial.ac.uk.
Jeffs
J A R
JAR
Department of Endocrinology and Metabolic Medicine, Division of Medicine, Faculty of Medicine, Imperial College London, St. Mary's Hospital, Mint Wing 2nd Floor, London, W2 1PG, UK.
Johnston
D G
DG
Department of Endocrinology and Metabolic Medicine, Division of Medicine, Faculty of Medicine, Imperial College London, St. Mary's Hospital, Mint Wing 2nd Floor, London, W2 1PG, UK.
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D015331:Cohort Studies; D005215:Fasting; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin