Dairy milk, regardless of fat content, protects against postprandial hyperglycemia-mediated impairments in vascular endothelial function in adults with prediabetes by limiting oxidative stress responses that reduce nitric oxide bioavailability.

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative-stress-dependent manner by decreasing nitric oxide (NO) bioavailability. Dairy milk, regardless of fat content, attenuates PPH, but whether this improves VEF by limiting oxidative stress responses that otherwise decrease NO bioavailability is not known. We hypothesized that nonfat and full-fat dairy milk would similarly improve VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO biosynthesis and bioavailability. A randomized, crossover trial was conducted in adults with prediabetes (n=22) who ingested glucose (75 g) dissolved in 473 ml of water (GLU), or glucose with an equal volume of nonfat dairy milk (NFM) or full-fat dairy milk (FFM). Prior to and at 30-min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured circulating biomarkers of glycemic control, oxidative stress and NO homeostasis. AUC for FMD and NO metabolites was lowest in GLU but relatively greater in NFM and FFM. Compared with GLU, AUCs for glucose, malondialdehyde, F-isoprostanes and endothelin-1 were similarly lower in dairy trials. Milk-mediated vasoprotection was accompanied by greater levels of plasma arginine and lower levels of asymmetric dimethylarginine and symmetric dimethylarginine. Postprandial insulin, lipids and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, regardless of its fat content, 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.