Published Online
on April 25, 2005

A more recent version of this article appeared on July 1, 2005

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Submitted on February 2, 2005
Revised on February 24, 2005

Advanced Glycation End Products Are Associated With Pulse Pressure in Type 1 Diabetes. The EURODIAB Prospective Complications Study

Miranda T. Schram; Casper G. Schalkwijk^*; Aart H. Bootsma; John H. Fuller; Nish Chaturvedi; Coen D.A. Stehouwer; EURODIAB Prospective Complications Study Group

From the Department of Internal Medicine (M.T.S., A.H.B.), Erasmus Medical Center, Rotterdam, the Netherlands; Departments of Internal Medicine (M.T.S., C.D.A.S.) and Clinical Chemistry (C.G.S.), VU University MC, Amsterdam, the Netherlands; Department of Epidemiology and Public Health (J.H.F.), University College, London, UK; International Centre for Circulatory Health and National Heart and Lung Institute (N.C.), Imperial College, London, UK; and Department of Medicine (C.D.A.S.), Academic Hospital Maastricht, the Netherlands.

Abstract--We investigated the associations of pulse pressure (a measure of arterial stiffness) with the early glycation products hemoglobin A1c (HbA1c) and Amadori albumin and the advanced glycation end products pentosidine, N-(carboxymethyl)lysine and N-(carboxyethyl)lysine in a large group of type 1 diabetic individuals of the EURODIAB Prospective Complications Study. We did a cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 543 (278 men) European individuals with type 1 diabetes diagnosed at <36 years of age. We used linear regression analyses to investigate the association of pulse pressure with glycation products. Pulse pressure was significantly associated with plasma levels of N-(carboxymethyl)lysine and N-(carboxyethyl)lysine but not with HbA1c, Amadori albumin, and urinary levels of pentosidine. Regression coefficients adjusted for age, sex, mean arterial pressure, and duration of diabetes were 0.09 mm Hg (P=0.003) per 1 µM/M lysine N-(carboxymethyl)lysine; 0.24 mm Hg (P=0.001) and -0.03 mm Hg (P=0.62) per 1 µM/M lysine N-(carboxyethyl)lysine (in individuals with and without complications, respectively; P interaction=0.002); and 0.50 mm Hg (P=0.16) per 1% HbA1c; 0.07 mm Hg (P=0.12) per 1 U/mL Amadori albumin; and 0.77 mm Hg (P=0.48) per 1 nmol/mmol creatinine pentosidine. In young type 1 diabetic individuals, arterial stiffness is strongly associated with the advanced glycation end products N-(carboxymethyl)lysine and N-(carboxyethyl)lysine. These findings suggest that the formation of advanced glycation end products is an important pathway in the development of arterial stiffness in young type 1 diabetic individuals.

Key words: diabetes mellitus • arteriosclerosis • elasticity • aging

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