I F Godsland1,2, J A R Jeffs3, D G Johnston3. 1. 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. 2. Wynn Institute, Division of Medicine, Imperial College London, London, UK. i.godsland@imperial.ac.uk. 3. 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.
Abstract
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.
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.
Authors: Muhammad Abdul-Ghani; Hussein Al Jobori; Giuseppe Daniele; John Adams; Eugenio Cersosimo; Curtis Triplitt; Ralph A DeFronzo Journal: Diabetes Date: 2017-06-13 Impact factor: 9.461