Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability

Abstract

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative stress-dependent manner by decreasing nitric oxide (NO^•) bioavailability. Dairy milk and its proteins attenuate PPH, but whether this improves VEF is unknown. We hypothesized that dairy milk, mediated by its whey and/or casein proteins, improves VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO^• bioavailability. A randomized, cross-over trial was conducted in adults with prediabetes (n=23) who ingested glucose (75 g, GLU) alone or with 473 mL of non-fat dairy milk (MILK) or isonitrogenous (16.5 g) amounts of whey (WHEY) or casein (CASEIN) in 473 mL of water. Prior to and at 30 min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured biomarkers of glycemic control, oxidative stress, and NO^• homeostasis. FMD_AUC decreased to the greatest extent during GLU, which was similarly improved in dairy trials. Compared with GLU, AUCs for glucose, malondialdehyde, F₂-isoprostanes, methylglyoxal, and endothelin-1 were similarly lower in dairy trials. Plasma arginine and NO^• metabolites were greater but methylated arginine metabolites were lower in dairy trials compared with GLU. Postprandial insulin, lipids, and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, mediated by its whey and casein proteins, attenuates PPH-mediated impairments in VEF by limiting oxidative stress. This improves NO^• bioavailability to the vascular endothelium by increasing arginine availability and limiting competitive inhibition on NO^• biosynthesis by asymmetric dimethylarginine. These findings support observational studies that dairy milk lowers cardiovascular disease risk.

Keywords: Arginine; Dairy milk; Flow-mediated dilation; Gastric emptying; Oral glucose challenge.