Loss of beta cell function as fasting glucose increases in the non-diabetic range |
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Authors: | Email author" target="_blank">I?F?GodslandEmail author J?A?R?Jeffs D?G?Johnston |
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Institution: | (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;(2) Wynn Institute, Division of Medicine, Imperial College London, London, UK |
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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.Abbreviations f fractional hepatic insulin throughput - FPG fasting plasma glucose - FSD fractional standard deviation - kc the plasma C-peptide elimination constant - ki the plasma insulin elimination constant - MFG mean fasting glucose - SG minimal model glucose effectiveness - SI minimal model insulin sensitivity In the course of this work, our colleague and co-author James Jeffs died unexpectedly after a short illness. His contribution will be greatly missed. |
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Keywords: | Beta cell function Fasting plasma glucose Insulin secretion Insulin sensitivity Modelling analysis |
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