HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahmed, N. Articles by Beisswenger, P. J. Search for Related Content PubMed PubMed Citation Articles by Ahmed, N. Articles by Beisswenger, P. J. Social Bookmarking                What's this?

Glycated and Oxidized Protein Degradation Products Are Indicators of Fasting and Postprandial Hyperglycemia in Diabetes

¹ Department of Biological Sciences, University of Essex, Colchester, Essex, U.K.
² Section of Endocrinology, Diabetes and Metabolism, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Address correspondence and reprint requests to Paul J. Beisswenger, MD, Professor of Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr., Lebanon, NH 03756. E-mail: paul.j.beisswenger{at}dartmouth.edu

OBJECTIVE—To assess the relative importance of fasting and postprandial hyperglycemia to vascular dysfunction in diabetes, we have measured indicators of glycation, oxidative and nitrosative stress in subjects with type 1 diabetes, and different postprandial glucose patterns.

RESEARCH DESIGN AND METHODS—Plasma and urinary levels of specific arginine- and lysine-derived advanced glycation end products, as well as oxidative and nitrosative products, were measured by liquid chromatography with triple quadrupole mass spectrometric detection (LC-MS/MS) after 2 months of treatment with insulin lispro or human regular insulin in 21 subjects participating in a cross-over study. Hb-bound early glycation (Amadori) products were also measured after each treatment period by high-performance liquid chromatography (fructosyl-valine Hb or HbA_1c [A1C]:Diamat) and fructosyl-lysine Hb by LC-MS/MS (A1C:fructosyl-lysine).

RESULTS—In diabetic patients, the concentrations of protein glycation and oxidation-free adducts increased up to 10-fold, while urinary excretion increased up to 15-fold. Decreasing postprandial hyperglycemia with lispro gave 10–20% decreases of the major free glycation adducts, hydroimidazolones derived from methylglyoxal and 3-deoxyglucosone, and glyoxal-derived N-carboxymethyl-lysine. No differences were observed in A1C:Diamat or A1C:fructosyl-lysine with lispro or regular insulin therapy in spite of significant decreases in postprandial glycemia with lispro.

CONCLUSIONS—We conclude that the profound increases in proteolytic products of proteins modified by advanced glycation endproducts in diabetic patients are responsive to changes in mean hyperglycemia and also show responses to changes in postprandial hyperglycemia.

Abbreviations: 3-DG, 3-deoxyglucosone • 3DG-H, 3-DG–derived hydroimidazolone N-(5-hydro-5-[2,3,4-trihydroxybutyl]-4-imidazolon-2-yl)ornithine • 3-NT, 3-nitrotyrosine • AGE, advanced glycation end product • CEL, N-carboxyethyl-lysine • CML, N-carboxymethyl-lysine • FPG, fasting plasma glucose • G-H1, glyoxal-derived hydroimidazolone N-(5-hydro-4-imidazolon-2-yl)ornithine • LC-MS/MS, liquid chromatography with triple quadrupole mass spectrometric detection • MetSo, methionine sulfoxide • MG-H1, methylglyoxal-derived hydroimidazolone N-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine • MPG, mean plasma glucose • NFK, N-formylkynurenine • PPG, postprandial glucose

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. A Williams, Y. S Choe, M. J Noss, C. J Baumgartner, and V. A Mustad Extract of Salacia oblonga lowers acute glycemia in patients with type 2 diabetes Am. J. Clinical Nutrition, July 1, 2007; 86(1): 124 - 130. [Abstract] [Full Text] [PDF]

				F. Galli Protein damage and inflammation in uraemia and dialysis patients Nephrol. Dial. Transplant., July 1, 2007; 22(suppl_5): v20 - v36. [Abstract] [Full Text] [PDF]

				A. Goldin, J. A. Beckman, A. M. Schmidt, and M. A. Creager Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury Circulation, August 8, 2006; 114(6): 597 - 605. [Abstract] [Full Text] [PDF]

				D. Dobler, N. Ahmed, L. Song, K. E. Eboigbodin, and P. J. Thornalley Increased Dicarbonyl Metabolism in Endothelial Cells in Hyperglycemia Induces Anoikis and Impairs Angiogenesis by RGD and GFOGER Motif Modification. Diabetes, July 1, 2006; 55(7): 1961 - 1969. [Abstract] [Full Text] [PDF]