Fiamoncini Jarlei, Donado-Pestana Carlos M, Duarte Graziela Biude Silva, Rundle Milena, Thomas Elizabeth Louise, Kiselova-Kaneva Yoana, Gundersen Thomas E, Bunzel Diana, Trezzi Jean-Pierre, Kulling Sabine E, Hiller Karsten, Sonntag Denise, Ivanova Diana, Brennan Lorraine, Wopereis Suzan, van Ommen Ben, Frost Gary, Bell Jimmy, Drevon Christian A, Daniel Hannelore
Department Food and Nutrition, Technische Universität München, Freising, Germany.
Food Research Center, Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Front Nutr. 2022 Jun 14;9:898782. doi: 10.3389/fnut.2022.898782. eCollection 2022.
Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as "at risk" for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.
摄入碳水化合物后胰岛素的分泌会影响众多代谢途径，这些代谢途径会同时改变糖、脂质和氨基酸在器官间通量的方向和数量。在本研究中，我们旨在识别与健康成年人群口服葡萄糖耐量试验（OGTT）不同反应相关的标志物。通过使用三种代谢物分析平台，我们评估了72名接受全面表型分析的健康志愿者血浆中总共202种代谢物的餐后反应，其中一半志愿者在三个月内参加了减肥计划。标准口服葡萄糖耐量试验（OGTT）作为饮食激发试验，以识别餐后代谢物谱的变化。尽管根据世界卫生组织标准被归类为健康人群，但根据餐后血糖谱仍识别出两个离散的组（A组和B组），且志愿者在性别和其他指标上分布均衡。A组个体的餐后血糖水平高出26%，葡萄糖清除延迟，并且空腹血浆中20多种先前在大型队列研究中确定的胰岛素抵抗和糖尿病已知生物标志物的浓度增加。通过典型餐后反应识别出的属于A组的志愿者可能被称为糖尿病前期，并被定义为有发展为胰岛素抵抗的“风险”。此外，选定脂肪酸和复合脂质、胆汁酸、氨基酸、酰基肉碱和诸如甘露糖等糖类的餐后变化显示，A组和B组个体的反应存在显著差异，且在整个240分钟的激发试验期内持续存在。几乎所有代谢物，包括葡萄糖和胰岛素，在试验结束时（240分钟时）都恢复到基线值，但有多种氨基酸以及那些与糖尿病发展相关的氨基酸除外。因此，分析空腹血样中的相应代谢物谱可能有助于早期识别这些有胰岛素抵抗风险的受试者，而无需进行OGTT。
