Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes

Abstract

We investigated whether serum levels of N-(carboxymethyl)lysine (CML), non-CML advanced glycation endproducts (AGEs), or pentosidine are associated with severity of diabetic microvascular complications in patients with Type 1 diabetes. Serum levels of CML, non-CML AGE, and pentosidine were measured by an enzyme-linked immunosorbent assay in 38 males and 47 females aged 31±8 years (mean±S.D.) with Type 1 diabetes for 18.7±7.0 years. There was a significant correlation between serum levels of CML or non-CML AGE and current HbA 1c level ( P<.01 and P<.05, respectively). The serum levels of non-CML AGE, but not CML or pentosidine, were significantly increased as normal renal status advanced to microalbuminuria, clinical nephropathy, and hemodialysis ( P<.0001) and were positively correlated with urinary albumin excretion (UAE) in patients with Type 1 diabetes ( P<.0001). A significant elevation of serum non-CML AGE was found in association with the severity of diabetic retinopathy ( P<.0001). We found in the present study that CML levels were also increased in the stage of simple retinopathy, the early stage of clinically evident retinopathy ( P<.05). Serum levels of non-CML AGE were significantly associated with the severity of diabetic nephropathy and retinopathy, suggesting a role of non-CML AGE in the progression of microvascular complications in patients with Type 1 diabetes. Since serum levels of CML were significantly increased in patients with simple retinopathy, CML may participate in the initiation of diabetic retinopathy.