Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is elevated in young, complication-free patients with Type 1 diabetes

Objectives: Elevated advanced glycation endproducts (AGEs) are implicated in diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of the most abundant AGEs in vivo. Our objective was to develop a time-saving, specific method to measure free MG-H in plasma and determine its levels in complication-free young individuals with Type 1 diabetes (T1DM). The relationship of plasma free MG-H to hemoglobin A1C (A1C) and plasma methylglyoxal levels was also determined. Design and methods: A solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, and free plasma MG-H levels were measured in 40 T1DM patients (DM group), aged 6-21 years, and 11 non-diabetics (ND group), 6-22 years. Methylglyoxal was measured using LC-MS/MS and A1C by a Tosoh G7 high-performance liquid chromatograph. Results: Our method showed high recovery, sensitivity and short run-time. Plasma free MG-H (nmol/L) was higher (p<0.001) ill the DM group (1318 +/- 569; mean +/- standard deviation) as compared to the ND group (583 +/- 419). Within the DM group, plasma free MG-H did not correlate with Plasma methylglyoxal or A1C. Conclusions: Our LC-MS/MS method to measure free MG-H in plasma may be useful for future clinical application. The increased levels of free MG-H observed in individuals with TIDM are not merely the result of short term changes in glucose or methylglyoxal, but may reflect long-term alterations to tissue proteins. (C) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.