Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes.
Increased production of advanced glycosylation end products (AGEs) and augmented oxidative stress may contribute to vascular complications in diabetes. Little is known about the formation and accumulation of AGEs in young patients with type 1 diabetes. The aim of the present study was to investigate whether AGE production and oxidative stress are augmented in young patients with type 1 diabetes at early clinical stages of the disease. Urine samples of 38 patients with type 1 diabetes [mean age (+/-SD), 12.8 +/- 4.5 y; diabetes duration, 5.7 +/- 4.3 y; HbA1c, 8.0 +/- 1.6%; urinary albumin excretion, 12.6 +/- 14.4 mg/g creatinine (Cr)] and those of 60 age-matched healthy control subjects were assayed for AGEs, pentosidine and pyrraline, and markers of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and acrolein-lysine. Of these four markers, urinary concentrations of pentosidine, 8-OHdG, and acrolein-lysine were significantly higher in the patients with diabetes than in the healthy control subjects. For the patient group, pentosidine correlated significantly with 8-OHdG and acrolein-lysine, and pyrraline correlated significantly with acrolein-lysine. Urinary pentosidine, 8-OHdG, and acrolein-lysine but not pyrraline correlated significantly with urinary albumin excretion. Patients with microalbuminuria (> or =15 mg/g Cr) showed significantly higher levels of all four markers than did normoalbuminuric patients and control subjects. The present study indicates that accumulation of AGEs, whose formation is closely linked to oxidative stress, and resultant endothelial dysfunction may start early in the course of type 1 diabetes. This means that the risk of vascular complications may be present at an early age and that the best possible glycemic control should be emphasized from the diagnosis of diabetes.
Tsukahara
Hirokazu
H
Department of Pediatrics, Fukui Medical University, Fukui 910-1193, Japan; htsuka@fmsrsa.fukui-med.ac.jp
Sekine
KyouchiI
K
Uchiyama
Mayumi
M
Kawakami
Hisako
H
Hata
Ikue
I
Todoroki
Yukiko
Y
Hiraoka
Masahiro
M
Kaji
Masayuki
M
Yorifuji
Tohru
T
Momoi
Toru
T
Yoshihara
Kazuhiro
K
Beppu
Masatoshi
M
Mayumi
Mitsufumi
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000171:Acrolein / Q000737:chemistry / Q000652:urine; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D008297:Male; D009646:Norleucine / Q000031:analogs & derivatives* / Q000652:urine; D018384:Oxidative Stress; D011758:Pyrroles / Q000652:urine; D012044:Regression Analysis
D017127:Glycation End Products, Advanced; D011758:Pyrroles; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D000171:Acrolein; D009646:Norleucine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D001120:Arginine; D003404:Creatinine; C062187:pentosidine; D003849:Deoxyguanosine; D008239:Lysine