Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes.
OBJECTIVE
To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications.


METHODS
The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21-B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion.


RESULTS
The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA(1c) than in those with normal HbA(1c) (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01).


CONCLUSIONS
Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.
Nishikawa
Takeshi
T
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan. takeshi@kaiju.medic.kumamoto-u.ac.jp
Sasahara
Takayuki
T
Kiritoshi
Shinsuke
S
Sonoda
Kazuhiro
K
Senokuchi
Takahumi
T
Matsuo
Tomoko
T
Kukidome
Daisuke
D
Wake
Nakayasu
N
Matsumura
Takeshi
T
Miyamura
Nobuhiro
N
Sakakida
Michiharu
M
Kishikawa
Hideki
H
Araki
Eiichi
E
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D017536:Carotid Artery, Common / Q000473:pathology; D003404:Creatinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D003925:Diabetic Angiopathies / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine; D003930:Diabetic Retinopathy / Q000145:classification; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D015415:Biomarkers; D007328:Insulin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D003849:Deoxyguanosine