Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia.
BACKGROUND
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 20-34 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).


CONCLUSIONS
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.
den Hollander
N C
NC
Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Mulder
D J
DJ
Graaff
R
R
Thorpe
S R
SR
Baynes
J W
JW
Smit
G P A
GP
Smit
A J
AJ
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology*; D003094:Collagen / Q000737:chemistry; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D005953:Glycogen Storage Disease Type I / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D018384:Oxidative Stress; D012306:Risk; D012867:Skin / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D017127:Glycation End Products, Advanced; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine