Amadori albumin in type 1 diabetic patients - Correlation with markers of endothelial function, association with diabetic nephropathy, and localization in retinal capillaries

Nonenzymatic glycation is increased in diabetes. Most studies so far have f ocused on the role of advanced glycation end products (AGEs) in vascular co mplications, whereas the role of early glycation Amadori-modified proteins, which is the predominant form of glycated proteins, has not been systemica lly investigated in humans. Fire developed an antiserum against glycated hu man serum albumin (HSA) and used this to study the role of early glycation products in vascular complications in type 1 diabetic patients. Amadori alb umin mas determined to be the recognition epitope of the antiserum. The ant ibody recognized a specific glucose adduct and a conformational component s pecific for human albumin in Amadori albumin, with no recognition of AGEs. Plasma Amadori albumin levels mere significantly higher in type 1 diabetic patients (n = 55) than in healthy control subjects (n = 60) (39.2 +/- 9.9 v s. 20.9 +/- 4.0 U/ml, P < 0.0005). Amadori albumin correlated with levels o f plasma markers of endothelial function von Willebrand factor (r = 0.29, P < 0.05) and vascular cell adhesion molecule-1 (r = 0.41, P < 0.005), but n ot soluble E-selectin. in addition, Amadori albumin immunoreactivity was de tected in the capillaries of retinas of diabetic patients. Plasma levels of Amadori albumin mere determined in a second group of type 1 diabetic patie nts with long-standing diabetes with (n = 199) or without (n = 192) diabeti c nephropathy. Patients with nephropathy had higher Amadori albumin levels than did those without it (50.9 +/- 9.5 vs. 45.1 +/- 6.3 U/ml, P < 0.0005). Age-, sex-, and diabetes duration-adjusted analyses showed that nephropath y was significantly associated with Amadori albumin with an odds ratio (OR [95% CI]) of 1.11 [1.08-1.15] per U/ml increase. After additional adjustmen t for levels of creatinine, glycated hemoglobin, cholesterol, triglycerides , blood pressure, preexistent retinopathy, and cardiovascular disease, Amad ori albumin continued to be significantly associated with nephropathy (OR 1 .06 [1.01-1.11]) per U/ml increase. Our results are consistent with a propo sed pathophysiological role of Amadori albumin in microvascular complicatio ns of type 1 diabetic patients.