It has been reported that the concentrations of both
pyrraline and
pentosidine, well-characterized
advanced glycation end products, are increased in the urine of diabetic patients. To determine factors that influence the urinary excretion of
pyrraline or
pentosidine, we compared
pyrraline or
pentosidine concentrations with
glycemic-control indexes, urinary
albumin excretion, and urinary beta2-microglobulin in patients with
type 2 diabetes. The study was conducted in 39 age-matched healthy control subjects and 50 diabetic patients, including 22 patients with normoalbuminuria, 15 with microalbuminuria, and 13 with macroalbuminuria. Both urinary
pyrraline and
pentosidine were measured in early-morning urine specimens with the use of high-pressure liquid chromatography. The urinary
pentosidine concentration was significantly higher in diabetic patients than in control subjects (P <.01). In contrast, the urinary
pyrraline concentration was significantly lower in diabetic patients than in control subjects (P <.001). Urinary
pentosidine concentrations were greater in diabetic patients with macroalbuminuria and microalbuminuria than in those with normoalbuminuria. However, urinary
pyrraline concentrations were significantly lower in diabetic patients with advanced nephropathy. Both the
hemoglobin A(1c) (HbA(1c)) and the preceding year's mean HbA(1c) were lower in patients with macroalbuminuria than in those with normoalbuminuria or microalbuminuria. Urinary
pyrraline, but not
pentosidine, showed a significantly positive correlation with the preceding year's mean HbA(1c) (P<0.01). Multivariate analysis disclosed that urinary beta-2-microglobulin was independently correlated with the urinary concentrations of
pentosidine and
pyrraline (P <.05 for both). We conclude that the urinary concentration of
pentosidine is greater in diabetic patients with overt nephropathy, whereas the urinary
pyrraline concentration is significantly lower in diabetic patients with overt nephropathy. Because urinary
pyrraline is more directly influenced by glycemia than by
pentosidine, the difference in
glycemic control among diabetic patients with various grades of nephropathy may be responsible for a dissociation between urinary
pyrraline and
pentosidine concentrations in patients with overt
diabetic nephropathy.