Acute macrovascular dysfunction in patients with type 2 diabetes induced by ingestion of advanced glycated β-lactoglobulins

Alin Stirban, Paraskevi Kotsi, Knut Franke, Ulf Strijowski, Weijing Cai, Christian Götting, Diethelm Tschoepe, Alin Stirban, Paraskevi Kotsi, Knut Franke, Ulf Strijowski, Weijing Cai, Christian Götting, Diethelm Tschoepe

Abstract

Objective: Recent 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 methods: In 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.

Results: Following 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 N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage.

Conclusions: In 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.

Trial registration: ClinicalTrials.gov NCT01456026.

Figures

Figure 1
Figure 1
Changes in FMD (A) and CML (B) after administration of AGE-BLG and C-BLG (mean and SEM). *P < 0.05 vs. before ingestion; ‡P < 0.05 vs. control protein ingestion.

References

    1. Vlassara H. Recent progress in advanced glycation end products and diabetic complications. Diabetes 1997;46(Suppl. 2):S19–S25
    1. Vlassara H, Palace MR. Glycoxidation: the menace of diabetes and aging. Mt Sinai J Med 2003;70:232–241
    1. Nin JW, Jorsal A, Ferreira I, et al. Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study. Diabetes Care 2011;34:442–447
    1. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813–820
    1. Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25:1055–1059
    1. Uribarri J, Woodruff S, Goodman S, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010;110:911–916, e12
    1. Vlassara H, Cai W, Crandall J, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA 2002;99:15596–15601
    1. Uribarri J, Peppa M, Cai W, et al. Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol 2003;14:728–731
    1. Uribarri J, Peppa M, Cai W, et al. Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. Am J Kidney Dis 2003;42:532–538
    1. Förster A, Kühne Y, Henle T. Studies on absorption and elimination of dietary maillard reaction products. Ann N Y Acad Sci 2005;1043:474–481
    1. Foerster A, Henle T. Glycation in food and metabolic transit of dietary AGEs (advanced glycation end-products): studies on the urinary excretion of pyrraline. Biochem Soc Trans 2003;31:1383–1385
    1. Erbersdobler HF, Faist V. Metabolic transit of Amadori products. Nahrung 2001;45:177–181
    1. Koschinsky T, He CJ, Mitsuhashi T, et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997;94:6474–6479
    1. Negrean M, Stirban A, Stratmann B, et al. Effects of low- and high-advanced glycation endproduct meals on macro- and microvascular endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Clin Nutr 2007;85:1236–1243
    1. Uribarri J, Stirban A, Sander D, et al. Single oral challenge by advanced glycation end products acutely impairs endothelial function in diabetic and nondiabetic subjects. Diabetes Care 2007;30:2579–2582
    1. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 1994;24:1468–1474
    1. Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag 2005;1:183–198
    1. Shimokawa H. Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol 1999;31:23–37
    1. Ahmed N, Mirshekar-Syahkal B, Kennish L, Karachalias N, Babaei-Jadidi R, Thornalley PJ. Assay of advanced glycation endproducts in selected beverages and food by liquid chromatography with tandem mass spectrometric detection. Mol Nutr Food Res 2005;49:691–699
    1. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–1115
    1. Birlouez-Aragon I, Saavedra G, Tessier FJ, et al. A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr 2010;91:1220–1226
    1. Grau M, Hendgen-Cotta UB, Brouzos P, et al. Recent methodological advances in the analysis of nitrite in the human circulation: nitrite as a biochemical parameter of the L-arginine/NO pathway. J Chromatogr B Analyt Technol Biomed Life Sci 2007;851:106–123
    1. Seftel AD, Vaziri ND, Ni Z, et al. Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS. Urology 1997;50:1016–1026
    1. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004;291:1978–1986
    1. Stirban A, Negrean M, Stratmann B, et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care 2006;29:2064–2071
    1. Kanabrocki EL, Murray D, Hermida RC, et al. Circadian variation in oxidative stress markers in healthy and type II diabetic men. Chronobiol Int 2002;19:423–439
    1. Blanco RA, Ziegler TR, Carlson BA, et al. Diurnal variation in glutathione and cysteine redox states in human plasma. Am J Clin Nutr 2007;86:1016–1023
    1. Zhang H, Tasaka S, Shiraishi Y, et al. Role of soluble receptor for advanced glycation end products on endotoxin-induced lung injury. Am J Respir Crit Care Med 2008;178:356–362
    1. Buetler TM, Latado H, Leclerc E, et al. Glycolaldehyde-modified β-lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE-expressing human cell lines. Mol Nutr Food Res 2011;55:291–299
    1. Inagawa H, Kohchi C, Soma G. Oral administration of lipopolysaccharides for the prevention of various diseases: benefit and usefulness. Anticancer Res 2011;31:2431–2436
    1. Sonaje K, Lin KJ, Tseng MT, et al. Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins. Biomaterials 2011;32:8712–8721

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever