Elevated postprandial glycemic responses (PPGRs) are associated with type 2 diabetes and cardiovascular disease. PPGRs to the same foods have been shown to vary between individuals, but systematic characterization of the underlying physiologic and molecular basis is lacking. We measured PPGRs using continuous glucose monitoring in 55 well-phenotyped participants challenged with seven different standard carbohydrate meals administered in replicate. We also examined whether preloading a rice meal with fiber, protein or fat (‘mitigators’) altered PPGRs. We performed gold-standard metabolic tests and multi-omics profiling to examine the physiologic and molecular basis for interindividual PPGR differences. Overall, rice was the most glucose-elevating carbohydrate meal, but there was considerable interindividual variability. Individuals with the highest PPGR to potatoes (potato-spikers) were more insulin resistant and had lower beta cell function, whereas grape-spikers were more insulin sensitive. Rice-spikers were more likely to be Asian individuals, and bread-spikers had higher blood pressure. Mitigators were less effective in reducing PPGRs in insulin-resistant as compared to insulin-sensitive participants. Multi-omics signatures of PPGR and metabolic phenotypes were discovered, including insulin-resistance-associated triglycerides, hypertension-associated metabolites and PPGR-associated microbiome pathways. These results demonstrate interindividual variability in PPGRs to carbohydrate meals and mitigators and their association with metabolic and molecular profiles.

餐后血糖反应 （PPGRs） 升高与 2 型糖尿病和心血管疾病有关。已证明相同食物的 PPGR 因个体而异，但缺乏对潜在生理和分子基础的系统表征。我们使用连续血糖监测测量了 55 名表型良好的参与者的 PPGRs，这些参与者重复服用了 7 种不同的标准碳水化合物餐。我们还检查了在米粉中预加载纤维、蛋白质或脂肪 （“缓解剂”） 是否改变了 PPGRs。我们进行了金标准代谢测试和多组学分析，以检查个体间 PPGR 差异的生理和分子基础。总体而言，大米是最能提高葡萄糖的碳水化合物餐，但存在相当大的个体间差异。对马铃薯 （potato-spikers） 具有最高 PPGR 的个体对胰岛素的抵抗力更强，β 细胞功能较低，而葡萄-spirks 对胰岛素更敏感。稻穗者更可能是亚洲个体，而面包獥者的血压更高。与胰岛素敏感的参与者相比，缓解剂在降低胰岛素抵抗患者的 PPGRs 方面效果较差。发现了 PPGR 和代谢表型的多组学特征，包括胰岛素抵抗相关的甘油三酯、高血压相关的代谢物和 PPGR 相关的微生物组途径。这些结果表明 PPGR 对碳水化合物膳食和缓解剂的个体间变异性及其与代谢和分子谱的关联。