Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy

Background: Diabetic nephropathy is a relatively common microvascular complication in people suffering from diabetic mellitus. Chronic hyperglycemia leads to the accumulation of advanced glycosylation end products (AGEs) that covalently trap extravasated serum proteins such as immunoglobulins, albumin, and LDL through glucose derived cross-linking to the extra vascular matrix. Methods: Serum fructosamine, glycosylated hemoglobin and percent glycosylation of IgG, IgA, IgM were measured in five different groups of human subjects: 50 normal individuals; 40 type 2 DM patients; 42 type I DM patients; 40 type 2 DM patients with nephropathy and 37 type I DM patients with nephropathy. Results: Patients with long-term history of diabetes and chronic hyperglycemia as well as suffering from diabetic nephropathy showed an increased glycosylated hemoglobin level and serum fructosamine as compared to those with diabetes mellitus and to the normal individuals. Glycosylation of IgG, IgA and IgM showed an increase in both type I and type 2 DM patients with nephropathy as compared to the diabetic patients without any complication. A positive correlation has been observed between glycosylated IgG and glycosylated hemoglobin (R-2 = 0.522, 0.5113, 0.7117, 0.673) in type I and type 2 DM without and with diabetic nephropathy, respectively, whereas correlation between glycosylated IgG and serum fructosamine was observed only in type I and type 2 DM without nephropathy (R-2 =0.7318, 0.5767). Conclusion. The present study suggests that glycosylation of IgG is an equivalent marker for advanced glycosylation as GHb and may have some role to play in the on onset of diabetic nephropathy by altering their immunoreactivity leading to micro vascular complications. (C) 2004 Elsevier B.V. All rights reserved.