Clinical implications of N epsilon-(carboxymethyl)lysine, advanced glycation end product, in children and adolescents with type 1 diabetes.

Abstract

AIM: The aim of this study was to investigate the relationship between serum levels of the glycoxylation product N(epsilon)-(carboxymethyl)lysine (CML) and development of chronic diabetic complications and degree of diabetic control in children and adolescents with type 1 diabetes.

METHODS: The serum levels of CML were measured in 87 patients with uncomplicated type 1 diabetes mellitus (12.7 +/- 4.6 years of age) and in seven patients with background retinopathy, microalbuminuria or neuropathy (18.2 +/- 5.2 years of age) and compared with those in 64 normal control subjects (12.6 +/- 5.2 years of age). The mean durations of diabetes in uncomplicated and complicated patients were 5.0 +/- 3.4 years (0.1-14 years), and 8.6 +/- 5.0 years (3.1-18 years), respectively. The serum levels of CML were measured by enzyme-linked immunosorbent assay using a monoclonal anti-CML antibody (6D12).

RESULTS: The serum levels of CML were significantly higher in the patient group than those in the control group; 0.85 +/- 0.37 (0.37-1.93) U/ml vs. 0.56 +/- 0.23 (0.15-1.05) U/ml (p < 0.001) and significantly higher in the patient group with chronic complications than those in patient group without chronic complications; 1.06 +/- 0.39 (0.72-1.78) U/ml vs. 0.83 +/- 0.36 (0.37-1.93) U/ml (p < 0.05). Weak, but statistically significant relationship between CML levels and haemoglobin A(1c) levels at the measurement of CML was observed (r = 0.29, p < 0.05).

CONCLUSIONS: Our data are suggesting that higher serum levels of CML are involved in the development of chronic diabetic complications, and serum levels of CML reflect the degree of diabetic control for a long duration in type 1 diabetic children and adolescents.