Serum levels of low molecular weight advanced glycation end products in diabetic subjects

AIMS: One of the principal theories of the development of diabetic complications proposes that increased levels of advanced glycation end products (AGE) are formed in diabetes by prolonged exposure of proteins, lipids and nucleotides to glucose. Such AGEs may contribute to the development of diabetic complications by a number of mechanisms. Circulating AGEs can be detected in serum, and in the present study, we analysed the clinical correlates of circulating serum low molecular weight AGE (LMW-AGE). METHODS: Serum LMW-AGE was measured in 106 non-diabetic and 499 diabetic subjects using fluorescence spectroscopy. Results were calibrated against an in-house AGE albumin preparation, and expressed as absolute fluorescence units (AFU). RESULTS: Serum LMW-AGE values were significantly higher in diabetic than non-diabetic subjects [median 7.5 (range 0-595.5) vs. 5.3 (1.0-15.5) AFU, P<0.01]. In the normal subjects, there were significant correlations between serum LMW-AGE and age (r=0.42, P<0.01) and serum creatinine (r=0.39, P<0.01). In the diabetic patients, serum LMW-AGE correlated significantly with age (r=0.315, P<0.01), systolic blood pressure (r=0.141, P=0.002), serum creatinine (r=0.449, P<0.01) and urinary albumin/creatinine ratio (ACR) (r=0.265, P<0.01). There was no correlation between serum LMW-AGE and HbA1c. On regression analysis, with serum LMW-AGE as the dependent variable, serum creatinine emerged as the most significant factor (t=8.1, P<0.01), followed by age (t=4.0, P<0.01) and ACR (t=2.9, P=0.004). There was no significant difference in serum LMW-AGE between those with and without retinopathy or in those with vascular disease. CONCLUSIONS: We conclude that circulating LMW-AGEs are increased in diabetic subjects. The major determinant appears to be renal dysfunction in the form of raised albumin/creatinine ratio or creatinine. There was no association with other markers of vascular disease or presence of diabetic complications.