Koopman A D M, Rutters F, Rauh S P, Nijpels G, Holst J J, Beulens J W, Alssema M, Dekker J M
EMGO+ Institute for health and care research, VUmc, Amsterdam, the Netherlands.
Department of Epidemiology and Biostatistics, VUmc, Amsterdam, the Netherlands.
PLoS One. 2018 Jan 11;13(1):e0191114. doi: 10.1371/journal.pone.0191114. eCollection 2018.
We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.
我们开展了首项前瞻性观察性研究，在基线时对口服葡萄糖耐量试验（OGTT）和混合餐试验（MMT）的肠促胰岛素反应与7年后空腹血糖水平变化之间的关联进行了研究，研究对象为基线时非糖尿病个体。我们使用了霍恩餐研究的数据；这是一项针对121名年龄在61.0±6.7岁受试者的基于人群的队列研究。在基线时测定了GIP和GLP-1反应，并表示为曲线下总面积和增量面积（tAUC和iAUC）。使用线性回归评估基线时肠促胰岛素反应与空腹血糖水平变化之间的关联。7年间血糖的平均变化为0.43±0.5 mmol/L。对于GIP，未观察到与空腹血糖水平变化有显著关联。相比之下，OGTT的GLP-1 iAUC反应处于中间和最高三分位数的参与者空腹血糖水平的升高（实际上是降低）明显较小；与最低三分位数的参与者相比，分别为-0.28（95%置信区间：-0.54；-0.01）mmol/L和-0.39（-0.67；-0.10）mmol/L。OGTT后tAUC GLP-1也观察到相同趋势（最高三分位数：与最低三分位数相比为-0.32（-0.61；-0.04）mmol/L）。MMT后GLP-1反应未观察到显著关联。总之，在我们基于非糖尿病人群的队列中，对OGTT的GLP-1反应较低与随访7年间空腹血糖水平的急剧升高有关。这表明GLP-1反应降低先于血糖恶化，可能在2型糖尿病的病因中起作用。
