Evaluation of Urinary 8-Hydroxydeoxy-Guanosine as a Novel Biomarker of Macrovascular Complications in Type 2 Diabetes
- Takeshi Nishikawa, MD, PHD1,
- Takayuki Sasahara, MD, PHD2,
- Shinsuke Kiritoshi, MD1,
- Kazuhiro Sonoda, MD1,
- Takahumi Senokuchi, MD1,
- Tomoko Matsuo, MD1,
- Daisuke Kukidome, MD1,
- Nakayasu Wake, MD, PHD1,
- Takeshi Matsumura, MD, PHD1,
- Nobuhiro Miyamura, MD, PHD1,
- Michiharu Sakakida, MD, PHD1,
- Hideki Kishikawa, MD, PHD3 and
- Eiichi Araki, MD, PHD1
- 1Department of Metabolic Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
- 2Insurance Omuta Tenryo Hospital, Fukuoka, Japan
- 3Kumamoto University Health Care Center, Kumamoto, Japan
Abstract
OBJECTIVE—To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications.
RESEARCH DESIGN AND 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 HbA1c than in those with normal HbA1c (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.
- CHD, coronary heart disease
- CIT, conventional insulin injection therapy
- IMT, intima-media thickness
- MIT, multiple insulin injection therapy
- MROS, mitochondrial reactive oxygen species
- 8-OHdG, 8-hydroxydeoxyguanosine
- ROS, reactive oxygen species
- U8-OHdG, urinary 8-OHdG:creatinine ratio
Footnotes
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Address correspondence and reprint requests to Takeshi Nishikawa, Department of Metabolic Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo Kumamoto 860-8556, Japan. E-mail: takeshi{at}kaiju.medic.kumamoto-u.ac.jp.
Received for publication 24 May 2002 and accepted in revised form 21 January 2003.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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