Acute Macrovascular Dysfunction in Patients With Type 2 Diabetes Induced by Ingestion of Advanced Glycated β-Lactoglobulins

Abstract

OBJECTIVERecent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSIn a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min.RESULTSFollowing the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in Nε-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage.CONCLUSIONSIn patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: meta-analysis of randomised controlled trials

“…Ten parallel 17 , 19 – 29 and seven randomised crossover studies 10 , 16 , 18 , 22 , 30 – 37 were included. The studies were conducted at research centres 10 , 15 , 16 , 18 , 24 , 27 , 34 – 37 , hospitals 20 , 28 , 30 , 32 , 33 and universities 17 , 19 , 21 – 23 , 25 , 26 , 29 , 31 in USA 17 , 20 – 24 , 27 – 29 , Australia 16 , 18 , Denmark 19 , 31 , Germany 10 , 34 – 37 , Mexico 25 , 26 , Spain 30 , 32 , 33 and France 15 . Twelve studies involved people without T2DM 15 , 17 , 18 , 21 , 23 , 26 – 33 , and six were in patients with T2DM 10 , 17 , 22 , 24 , 25 , 34 – 37 .…”

“…The studies were conducted at research centres 10 , 15 , 16 , 18 , 24 , 27 , 34 – 37 , hospitals 20 , 28 , 30 , 32 , 33 and universities 17 , 19 , 21 – 23 , 25 , 26 , 29 , 31 in USA 17 , 20 – 24 , 27 – 29 , Australia 16 , 18 , Denmark 19 , 31 , Germany 10 , 34 – 37 , Mexico 25 , 26 , Spain 30 , 32 , 33 and France 15 . Twelve studies involved people without T2DM 15 , 17 , 18 , 21 , 23 , 26 – 33 , and six were in patients with T2DM 10 , 17 , 22 , 24 , 25 , 34 – 37 . The majority (n = 13) of the studies used high AGE diets which were two or more times higher in AGE content than the low AGE diets 1 , 10 , 15 , 17 – 19 , 22 – 24 , 27 – 37 and the rest used high AGE diets that were less than two times higher in AGE content than the low AGE diets.…”

“…The majority (n = 13) of the studies used high AGE diets which were two or more times higher in AGE content than the low AGE diets 1 , 10 , 15 , 17 – 19 , 22 – 24 , 27 – 37 and the rest used high AGE diets that were less than two times higher in AGE content than the low AGE diets. The duration of 11 studies was ≥4 weeks 15 , 17 , 19 – 29 , four for 2–4 weeks 16 , 18 , 22 , 30 , 32 , 33 and two for <2 weeks 10 , 31 , 34 – 37 .…”

The Inhibition of Advanced Glycation End Products by Carnosine and Other Natural Dipeptides to Reduce Diabetic and Age‐Related Complications

“…Yeh, Yang, Pai, Wu, and Chen () administered methylglyoxal‐derived AGEs to mice for 16 wk and found that the treatment accelerated the accumulation of AGEs in the kidneys, increased the expression of inflammasome‐related proteins, and decreased the levels of nitric oxide synthase and nitric oxide. In patients with type 2 diabetes, oral administration of AGE‐modified β‐lactoglobulin significantly impaired macrovascular function and decreased nitric oxide bioavailability, although the effect was transient (Stirban et al., ). Many studies on AGEs have been heavily suggested to play a role in the progression of many age‐related and diabetic complications.…”

Vascular Effects of Dietary Advanced Glycation End Products

“…We therefore performed a randomized, double-blind, controlled, cross-over study that aimed at investigating the acute effects of dietary AGEs resulting from nonenzymatic glycation during heating of beta-lactoglobulins (a protein class frequently encountered in food) and compared these effects to nonglycated, but heated beta-lactoglobulins (BLG) [ 84 ]. Thus, the sole difference between the 2 protein preparations was the advanced protein glycation.…”