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

J Diabetes Complications. Jan-Feb 2003;17(1):16-21. doi: 10.1016/s1056-8727(02)00183-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / blood
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Blood Pressure
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetic Angiopathies / blood*
  • Diabetic Nephropathies / blood
  • Diabetic Retinopathy / blood
  • Female
  • Glycated Hemoglobin A / analysis
  • Glycation End Products, Advanced / blood*
  • Humans
  • Logistic Models
  • Lysine / analogs & derivatives*
  • Lysine / blood*
  • Male
  • Renal Dialysis


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • N(6)-carboxymethyllysine
  • Arginine
  • pentosidine
  • Lysine