Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia

N. C. den Hollander, D. J. Mulder, R. Graaff, S. R. Thorpe, J. W. Baynes, G. P. A. Smit and A. J. Smit

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Abstract

Introduction  

Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from lifetime low plasma glucose levels and decreased oxidative stress.

Methods  

In 8 GSD Ia patients (age 20–24 years) and 30 matched controls we measured carotid intima-media thickness (IMT), skin autofluorescence (AF; a non-invasive index for AGEs), and specific AGEs (pentosidine, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL)) and collagen linked fluorescence (CLF, measured at excitation/emission wavelength combinations of 328/378 and 370/440 nm) in skin samples.

Results  

Carotid IMT was significantly lower in GSD Ia patients. Skin AF did not differ between patients and controls. The skin samples showed higher CEL levels in the patient group (p=0.008), but similar levels of pentosidine, CML, and CLF. In the total group, skin AF correlated with CML (r=0.39, p=0.031), CLF 328/378 nm (r=0.53; p=0.002) and CLF 370/440 nm (r=0.60; p=0.001). In the control group, AF also correlated with the maximum carotid IMT (r=0.6; p=0.004).

Conclusion  

Although our data confirm that GSD Ia patients present with a reduced burden of atherosclerosis, this phenomenon cannot be explained by differences in AGE accumulation as measured in the skin.
Communicating editor: René Santer
Competing interests: R. Graaff and A.J. Smit are founders of DiagnOptics B.V., The Netherlands, manufacturer of the AGE- Reader
References to electronic databases: Glycogen storage disease type Ia (GSD Ia): OMIM +232200. Glucose-6-phosphatase (G6Pase) EC 3.1.3.9.

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