Elevation of N-(carboxymethyl)valine residue in hemoglobin of diabetic patients. Its role in the development of diabetic nephropathy.
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


METHODS
BALB/c mice were immunized with carboxy-methylated 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 69 +/- 1.5 vs. 5.2 +/- 0.4%, P < 0.0001).


RESULTS
A monoclonal antibody against CMV-Hb beta-chain NH2-terminal and an assay method for measurement for CNMV-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 +/- 0.9 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.
Uchimura
T
T
Department of Laboratory and Molecular Medicine, Kagoshima University School of Medicine, Kagoshima City, Japan.
Nakano
K
K
Hashiguchi
T
T
Iwamoto
H
H
Miura
K
K
Yoshimura
Y
Y
Hanyu
N
N
Hirata
K
K
Imakuma
M
M
Motomiya
Y
Y
Maruyama
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D015374:Biosensing Techniques; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors; D014633:Valine / Q000032:analysis*
D000911:Antibodies, Monoclonal; D002784:Cholesterol; D003404:Creatinine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006454:Hemoglobins; D014633:Valine; C120200:N-(carboxymethyl)valine