Exp Clin Endocrinol Diabetes 2014; 122 - P011
DOI: 10.1055/s-0034-1372028

Altered methylglyoxal metabolism identifies patients with late diabetic complications

JB Groener 1, F Blachutzik 1, D Oikonomou 1, E Kliemank 1, T Fleming 1, PP Nawroth 1
  • 1University of Heidelberg, Department of Medicine I and Clinical Chemistry, Heidelberg, Germany

Introduction: Since glucose lowering only partially prevents late diabetic complications, other indices are needed to distinguish between diabetics with and without complications.

To estimate whether the formation of methylglyoxal (MG), a reactive metabolite formed under conditions of increased glycolytic flux, and triose phosphates (TP) correlates with the severity of late diabetic complications, changes in glucose-dependent production of TP and MG were determined in red blood cells (RBC) of diabetics with severe and moderate diabetic complications as well as non-diabetic controls.

Methods: Isolated RBC from diabetic (N = 30) and non-diabetic individuals (N = 21) were incubated in Krebs-Ringer phosphate buffer with 5 – 100mM glucose at 37 °C with samples taken at 0, 1 and 6 hrs. The concentration of TP and MG was determined by end-point enzymatic-assay and HPLC, respectively.

Results: The production of TP and MG increased in a dose dependent manner with respect to glucose for both diabetics and controls. Diabetics were found to have higher levels of MG compared to healthy controls. No association was observed with respect to blood glucose and HbA1c, pointing to a glucose and HbA1c independently acquired error of toxic metabolite metabolism.

While controls had MG concentrations of 0.054 pmol Hbmg-1 mmol glucose-1, diabetics without complications had lower levels of 0.025 pmol Hbmg-1 mmol glucose-1 (p = 0.050). Most important, diabetics with late complications showed a trend towards increased levels of 0.116 pmol Hbmg-1 mmol glucose-1 (p = 0.109 compared to diabetics without complications). When studying TP, a similar pattern was observed.

Conclusion: This data indicates that the risk of complications in type 2 diabetics is not well recognized by glucose and HbA1c alone. Looking at a dynamic assay for MG formation and detoxification, a more precise risk assessment could become possible, further supporting the assumption that toxic metabolites are driving late diabetic complications.