Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy Kiran Kalia * , Seema Sharma, Kinnari Mistry Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar-388120 Gujarat, India Received 10 February 2004; received in revised form 19 April 2004; accepted 19 April 2004 Abstract 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 1 DM patients; 40 type 2 DM patients with nephropathy and 37 type 1 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 1 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 1 and type 2 DM without and with diabetic nephropathy, respectively, whereas correlation between glycosylated IgG and serum fructosamine was observed only in type 1 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. D 2004 Elsevier B.V. All rights reserved. Keywords: Glycosylated immunoglobulins; Fructosamine; Glycosylated hemoglobin; Diabetic nephropathy 1. Introduction Diabetic nephropathy, a complication of diabetes, is the most devastating and resource-consuming com- plication in patients with diabetes throughout the world. The cardinal lesion of diabetic nephropathy resides in renal glomeruli (diabetic glomerulosclero- sis). Hyperglycemia is responsible for the develop- ment and progression of diabetic nephropathy through metabolic derangements, including increased oxida- tive stress, renal polyol formation, activation of pro- tein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and accumulation of advanced glycosylation end products (AGEs) as well as such homodynamic factors as systemic hypertension and increased intraglomerular pressure [1], although these studies did not define the mechanisms responsible for secondary complications in type 1 and type 2 DM. 0009-8981/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.cccn.2004.04.016 * Corresponding author. Tel.: +91-2692-226863; fax: +91-2692- 226865. E-mail address: kirankalia _ in@yahoo.com (K. Kalia). www.elsevier.com/locate/clinchim Clinica Chimica Acta 347 (2004) 169 – 176