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(Hypertension. 2005;46:232.)
© 2005 American Heart Association, Inc.

Fifth International Workshop on Structure and Function of Large Arteries

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 on behalf of the 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.

Correspondence to Casper G. Schalkwijk, PhD, Department of Medicine, Academic Hospital Maastricht, 6202 AZ Maastrich, The Netherlands.

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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