Amadori albumin in type 1 diabetic patients: Correlation with markers of endothelial function, association with diabetic nephropathy, and localization in retinal capillaries

Casper G. Schalkwijk*, Nicole Ligtvoet, Harry Twaalfhoven, Agnes Jager, Harriët G.T. Blaauwgeers, Reinier O. Schlingemann, Lise Tarnow, Hans Henrik Parving, Coen D.A. Stehouwer, Victor W.M. Van Hinsbergh

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

146 Citations (Scopus)


Nonenzymatic glycation is increased in diabetes. Most studies so far have focused on the role of advanced glycation end products (AGEs) in vascular complications, whereas the role of early glycation Amadori-modified proteins, which is the predominant form of glycated proteins, has not been systemically investigated in humans. We developed an antiserum against glycated human serum albumin (HSA) and used this to study the role of early glycation products in vascular complications in type 1 diabetic patients. Amadori albumin was determined to be the recognition epitope of the antiserum. The antibody recognized a specific glucose adduct and a conformational component specific for human albumin in Amadori albumin, with no recognition of AGEs. Plasma Amadori albumin levels were significantly higher in type I diabetic patients (n = 55) than in healthy control subjects (n = 60) (39.2 ± 9.9 vs. 20.9 ± 4.0 U/ml, P < 0.0005). Amadori albumin correlated with levels of plasma markers of endothelial function von Willebrand factor (r = 0.29, P < 0.05) and vascular cell adhesion molecule-1 (r = 0.41, P < 0.005), but not soluble E-selectin. In addition, Amadori albumin immunoreactivity was detected in the capillaries of retinas of diabetic patients. Plasma levels of Amadori albumin were determined in a second group of type 1 diabetic patients with long-standing diabetes with (n = 199) or without (n = 192) diabetic nephropathy. Patients with nephropathy had higher Amadori albumin levels than did those without it (50.9 ± 9.5 vs. 45.1 ± 6.3 U/ml, P < 0.0005). Age-, sex-, and diabetes duration-adjusted analyses showed that nephropathy was significantly associated with Amadori albumin with an odds ratio (OR [95% CI]) of 1.11 [1.08-1.15] per U/ml increase. After additional adjustment for levels of creatinine, glycated hemoglobin, cholesterol, triglycerides, blood pressure, preexistent retinopathy, and cardiovascular disease, Amadori albumin continued to be significantly associated with nephropathy (OR 1.06 [1.01-1.11]) per U/ml increase. Our results are consistent with a proposed pathophysiological role of Amadori albumin in microvascular complications of type 1 diabetic patients.

Original languageEnglish
Pages (from-to)2446-2453
Number of pages8
Issue number12
Publication statusPublished - Dec 1999
Externally publishedYes

Bibliographical note

This work was supported by a grant from the Dutch Kidney Foundation (C98.1786), Diabetes Fonds Netherland (95.103),
Praeventiefonds (28-2622-2), and a University Stimulating Fund grant of the Vrije Universiteit, Amsterdam. C.D.A.S. is
supported by a Clinical Research Fellowship from the Diabetes Fonds Netherland and the Netherlands Organization for
S c i e n t i fic Research (NWO).


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