Glycated immunoglobulin M in diabetic patients

Abstract

Measurement of glycation levels on isolated immunoglobulin M (IgM), a short half-life protein, could be an index of glycaemic control. We determined glycated IgM levels in a diabetic patients population as compared to control non-diabetic subjects in a cross-sectional and longitudinal study. For that purpose we developed a precipitation method for IgM purification, measured glycation on the purified protein by a nitroblue tetrazolium assay and correlated glycated IgM, glycated haemoglobin (HbA1c) and fructosamine rates. The purification method we developed comprises dextran sulfate-CaCl2, ammonium sulfate and polyethylene glycol precipitations and it allows extraction of IgM free of contaminants as shown by immunoelectrophoresis. Glycated IgM levels were 8.65 +/- 0.15 nmol deoxymorpholinofructose (DOMF) equivalents/mg protein for non-diabetic subjects (n = 30) and 12.08 +/- 0.60 nmol DOMF equivalents/mg protein (n = 67) for diabetic patients. Diabetic patients had then a 40% rise in glycated IgM (p < 0.0005). In a longitudinal study with patients undergoing treatment aimed at improving their metabolic control, glycated IgM levels decreased significantly (p < 0.001) between the day of admission and the fifth day. Average rate of fall was 13% with a range of 3.0 to 22.0% (n = 28). Glycated IgM clearly responds more rapidly than fructosamines which fell by 7.0% and than HbA1c, which showed a rate of fall of 3.9% in the same period. A significant positive correlation was found between these parameters, being stronger between glycated IgM and fructosamines. This method could provide an alternative approach as a short-term marker of glycaemic control for clinical trials.