Low-molecular-weight AGEs are associated with GFR and anemia in patients with type 2 diabetes

Abstract

Background. Advanced glycation end products (AGEs) are implicated in the development and progression of diabetic nephropathy. We examined the predictors of low-molecular-weight (LMW) AGEs in a cross-sectional survey of 604 patients with type 2 diabetes in a single clinic. Methods. A clinical history and results of routine blood and urine testing were obtained for all patients over a 2-year period. Fluorescent LMW AGEs were estimated in serum samples taken concurrently, using an established flow injection method. Predictors of LMW AGEs were identified using multiple regression analysis. Results. LMW AGEs were 34% higher in patients with diabetes than nondiabetic volunteers from the same community (P < 0.001). Independent predictors for LMW AGEs in patients with diabetes were glomerular filtration rate (GFR) and hemoglobin (both P < 0.001). While patients with renal impairment and anemia had the highest levels of LMW AGEs, both GFR and hemoglobin remained predictive when patients with a serum creatinine or hemoglobin within the "normal range" were analyzed separately. Patients with hyperfiltration had significantly lower LMW AGEs than those with normal renal function. Gender was also a significant independent predictor of LMW AGEs in patients without anemia. However, LMW AGEs were not associated with metabolic control or the presence of macrovascular disease. Conclusion. Circulating levels of LMW AGEs are elevated in patients with diabetes, especially those with impaired renal function or anemia. These findings extend the evidence for an association between AGEs and progressive renal injury in patients with type 2 diabetes. Whether LMW AGEs contribute to, or are a marker of, renal damage needs to be established by prospective studies.