Elevation of N-(Carboxymethyl)valine Residue in Hemoglobin of Diabetic Patients
Its role in the development of diabetic nephropathy
- Tomonori Uchimura, MD1,
- Kazushi Nakano, MD1,
- Teruto Hashiguchi, MD1,
- Hisahiko Iwamoto, MSc2,
- Keisuke Miura, MSc2,
- Yoshimichi Yoshimura, PhD2,
- Naohiro Hanyu, MSc3,
- Koichiro Hirata, MSc3,
- Misturu Imakuma, MD4,
- Yoshihiro Motomiya, MD5 and
- Ikuro Maruyama, MD, PhD1
- 1Department of Laboratory and Molecular Medicine, Kagoshima University School of Medicine, Kagoshima
- 2Department of Research and Development for Diagnostics, A&T Corp., Hasaki, Ibaraki
- 3Tsukuba Research Laboratories, Tokuyama Corp., Tsukuba, Ibaraki
- 4Kimotsuki-gun Ishikai Hospital, Onejime, Kagoshima
- 5Suiyukai Clinic, Kashihara, Nara, Japan
Abstract
OBJECTIVE—Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein, we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathy.
RESEARCH DESIGN AND METHODS—BALB/c mice were immunized with carboxymethylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 ± 12.0 vs. 61.1 ± 13.2 years, NS; HbA1c 6.9 ± 1.5 vs. 5.2 ± 0.4%, P < 0.0001).
RESULTS—A monoclonal antibody against CMV-Hb β-chain NH2-terminal and an assay method for measurement for CMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 ± 6.9 vs. 12.7 ± 6.9 pmol CMV/mg Hb, P < 0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed.
CONCLUSIONS—We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.
- CM-Hb, carboxymethylated Hb
- CML, carboxymethyl lysine
- CMV, N-(carboxymethyl)valine
- CMV-Hb, N-(carboxymethyl)valine of Hb
- HPLC, high-performance liquid chromatography
- HAS, human serum albumin
- RAGE, receptor for AGE
- RU, resonance unit
- SPR, surface plasmon resonance
- TEA, triethylamine
Footnotes
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Address correspondence and reprint requests to Ikuro Maruyama, Department of Laboratory and Molecular Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima City, 890-8520, Japan. E-mail: ucchii{at}khosp2.kufm.kagoshima-u.ac.jp.
Received for publication 28 September 2000 and accepted in revised form 23 January 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
