Application of Comparative Lipidomics to Elucidate Postprandial Metabolic Excursions Following Dairy Milk Ingestion in Individuals with Prediabetes

Nutrient-dense dairy foods are an important component of a healthy diet. Recommendations, however, advise non- and low-fat dairy foods despite controversy concerning whether full-fat dairy foods adversely impact cardiometabolic health. Therefore, in this study, our objective is to examine the differential plasma lipidomic responses to non-fat or full-fat milk ingestion during postprandial hyperglycemia. Seven adults with prediabetes completed a randomized cross-over study in which glucose was consumed alone or with non-fat or full-fat dairy milk. Plasma samples collected at 90 min and 180 min post milk ingestion were used to perform untargeted lipidomics analysis. A total of 332 lipids from 20 classes and five lipid categories were detected at different time points during the postprandial period. Dairy milk, especially non-fat milk, protected against lipid changes otherwise induced by glucose ingestion. Co-ingestion of dairy milk with glucose, regardless of fat content, significantly altered lipid profiles although full-fat milk more substantially modulated lipid profiles. For the identified lipid biomarkers, 68.0% and 66.7% of the lipids significantly increased at 90 and 180 min, respectively, while phosphatidylcholines (GPs) contributed most for the significant increase. Comparative lipidomics analysis indicated that both types of dairy milk induced significant changes in several lipid pathways, including glycerophospholipid metabolism and α-linolenic acid metabolism, to protect against postprandial hyperglycemia. In summary, our comparative lipidomics results suggested that dairy milk-mediated lipid modulation may be an effective dietary approach to reduce the risk of metabolic diseases among those with prediabetes.