Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes

A time-delayed fluorescence immunoassay was developed for the determination of serum levels of methylglyoxal (MG)-derived hydroimidazolone using a monoclonal antiserum raised against Nα-acetyl-Nδ-(5-hydro-5-methyl)-4-imidazolone, Europium-labeled anti-mouse IgG antiserum as indicator, and MG modified bovine serum albumin (BSA) as standard. Serum levels of hydroimidazolone were measured in 45 patients with type 2 diabetes aged 59.4 ± 6.1 (mean ± SD) years and with duration of diabetes of 7.3 ± 3.1 years, and in 19 nondiabetic controls aged 56.3 ± 4.3 years. The serum levels of hydroimidazolone were significantly higher in patients compared to controls: median, 3.0 (5-95 percentile, 1.6 to 5.4) U/mg protein versus 1.9 (1.2 to 2.8) U/mg protein (P = .0005). Significant positive correlations were observed between the serum levels of hydroimidazolone and serum levels of advanced glycation end products (AGEs), measured with a polyclonal anti-AGE antibody: r = 0.59 for patients (P < .0001), and r = 0.65 for controls (P = .002). Similarly, significant correlations were also found between serum levels of hydroimidazolone and N^ε-(carboxymethyl)-lysine (CML): r = 0.36 in patients and r = 0.55 for controls (both P = .02). Serum hydroimidazolone levels did not correlate with fasting plasma glucose or hemoglobin A_1c (HbA_1c) levels. The observed differences between patients with diabetes and nondiabetic controls seem to be comparable to differences measured for other AGE compounds.