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

Diabetes Care. 2001 May;24(5):891-6. doi: 10.2337/diacare.24.5.891.

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 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Biosensing Techniques
  • Blood Urea Nitrogen
  • Cholesterol / blood
  • Creatinine / blood
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / physiopathology*
  • Diabetic Nephropathies / physiopathology*
  • Erythrocytes / chemistry
  • Female
  • Glycated Hemoglobin / analysis
  • Glycation End Products, Advanced / blood
  • Hemoglobins / chemistry*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Reference Values
  • Regression Analysis
  • Risk Factors
  • Valine / analysis*

Substances

  • Antibodies, Monoclonal
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Hemoglobins
  • N-(carboxymethyl)valine
  • Cholesterol
  • Creatinine
  • Valine