N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of renal function.

Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine (CML) have been implicated in the development and progression of diabetic nephropathy. The aim of the present study is to investigate AGE levels in patients with type 2 diabetes with special regard to the role of renal impairment. Serum and urine CML levels (using a newly developed enzyme-linked immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109 patients with type 2 diabetes. Patients were divided into groups with normal and impaired renal function. We found elevated serum fluorescent AGE and CML levels, as well as decreased urinary CML excretion rates, in patients with diabetes with renal impairment, but not those with normal renal function. In the presence of impaired renal function, serum CML and fluorescent AGE levels showed a significant inverse relation with creatinine clearance and a significant direct correlation with each other. No relationship could be found between serum AGE levels and parameters of blood glucose control or the presence of the following clinical complications: ischemic heart disease, diabetic retinopathy, and neuropathy. We conclude that the decline in renal function leads to increased serum AGE levels in patients with type 2 diabetes.