Loss of beta cell function as fasting glucose increases in the non-diabetic range
Loss of beta cell function as fasting glucose increases in the non-diabetic range
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DOI：
10.1007/s00125-004-1454-z
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发表时间：
2004-07-01
期刊：
影响因子：
8.2
通讯作者：
Johnston, DG
中科院分区：
文献类型：
--
作者：
Godsland, IF;Jeffs, JAR;Johnston, DG
目的/假说。我们的目的是确定胰胰岛素分泌，特别是第一阶段胰岛素释放开始下降的血糖水平。在IVGTT期间测量了553名非糖尿病患者空腹血糖浓度的血浆葡萄糖和胰岛素浓度。对466名男性的c肽也进行了估计。IVGTT初期和晚期胰岛素分泌通过以下方式评估：(i)循环胰岛素反应；（ii）血浆c肽浓度总体参数反褶积分析；（iii）利用胰岛素和c肽浓度的组合模型。胰岛素敏感性和消除的测量也通过模型分析得出。随着空腹血糖（FPG）的升高，三种方法IVGTT一期胰岛素分泌量分别下降73%、71%和68%。变化点回归测定的FPG值开始下降时分别为4.97、5.16和5.42 mmol/l。FPG浓度高于6.0 mmol/l时，后期胰岛素分泌对葡萄糖的敏感性下降。胰岛素消除，而不是胰岛素敏感性，在fpg中有所不同。第一阶段胰岛素反应开始逐渐丧失的FPG浓度范围可能低至5.0 ~ 5.4 mmol/l，当FPG浓度高于6.0 mmol/l时，晚期胰岛素反应下降。
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.