The Relationship of Serum Soluble Receptor for Advanced Glycation End Products (sRAGE) and Carboxymethyl Lysine (CML) to the Incidence of Diabetic Nephropathy in Persons With Type 1 Diabetes

We hypothesized that persons with type 1 diabetes with higher serum levels of carboxymethyl lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) are at a higher risk of developing incident diabetic nephropathy (DN). We examined this hypothesis using data from up to four follow-up examinations over a 22-year period in persons with type 1 diabetes participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We also examined the relationship of CML and sRAGE to mortality. Descriptions of the cohort, participation statistics, and reasons for nonparticipation have appeared elsewhere (1). Of 1,210 persons with type 1 diabetes receiving care in an 11-county area of south central Wisconsin in 1979–1980, 996 were examined in 1980–1982. The individuals were 3–79 years of age with type 1 diabetes duration of 1–59 years. These persons participated in up to six follow-up examinations in 1984–1986 ( n = 903), 1990–1992 ( n = 816), 1994–1996 ( n = 667), 2000–2001 ( n = 567), 2005–2007 ( n = 520), and 2012–2014 ( n = 414). The tenets of the Declaration of Helsinki were followed, and institutional review board approval was obtained from the University of Wisconsin–Madison. Written informed consent was obtained. Starting with the third examination in 1990–1992 and continuing with follow-up examinations, serum was collected, processed, and frozen at −80°C. Serum sRAGE and CML levels were measured …