2002 Fiscal Year Final Research Report Summary
The role of mitochondria-derived reactive oxygen species in the pathogenesis of diabetic complications
| Project/Area Number |
13671195
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
TOYONAGA Tetsushi Kumamoto University, Department of Medicine, Assistant, 医学部, 助手 (60295128)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Eiichi Kumamoto University, Department of Medicine, Professor, 医学部, 教授 (10253733)
MIYAMURA Nobuhiro Kumamoto University, University Hospital, Assistant, 医学部附属病院, 講師 (40274716)
NISHIKAWA Takeshi Kumamoto University, Department of Medicine, Assistant, 医学部, 助手 (70336212)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Diabetic complications / Oxidative stress / Mitochondria / 8-hydroxydeoxyguanosine / Manganese superoxide dismutase |
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| Research Abstract |
Recently we proposed that hyperglycemia-induced ROS production from mitochondria is a key event in the development of diabetic complications (Nishikawa et al. 2000; Nature 404: 787-90). During 2001-2002, we have performed below project based on our hypothesis.
Objective - To evaluate urinary 8-hydroxydeoxyguanosine as a marker for the progression of diabetic macroangiopathic complications.
Research design and methods - The content of urinary 8-hydroxydeoxyguanosine (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 mellitus including 32 patients, who had been nominated for Kumamoto Study (Shichiri M, et al, Diabetes Care 23 Suppl 2:B21-29, 2000). In addition, the patients from Kumamoto were further evaluated the effect of intensive insulin therapy on urinary 8-OHdG excretion.
Results - The urinary 8-OHdG/creatinine ratio (U8-OHdG) was 2.5 fold elevated in patients with increased HbA1c compared to those with normal HbA1c (p<0.05). In addition, U8-OHdG was 2.3 fold elevated 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 elevated in patients with simple retinopathy (p<0.05) and those with advanced retinopathy (p<0.01) compared to patients without retinopathy. Similarly, U8-OHdG was significantly elevated in patients with albuminuria (p<0.01). Furthermore, U8-OHdG was significantly lower in multiple insulin injection therapy group compared with conventional insulin injection therapy group in patients from Kumamoto Study (p<0.01).
Conclusions - Hyperglycemia suggested to be independently increase 8-OHdG in type 2 diabetic patients. 8-OHdG is a useful biomarker of not only microvascular but also microvascular complications in patients with type 2 diabetes.
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[Publications] Nishikawa T, Sasahara T, Kiritoshi S, Sonoda K, Senokuchi T, Matsuo T, Kukidome D, Wake N, Matsumura T, Miyamura N, Sasakida M, Kishikawa H, Araki E: "Evaluation of urinary 8-hydroxydeoxyguanosine as a novel biomarker of macrovascular complications in type 2 diabetes"Diabetes Care. in press. (2003)
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