title: Plasma levels of AGE peptides in type 1 diabetic patients are associated with serum creatinine and not with albumin excretion rate: possible role of AGE peptide-associated endothelial dysfunction.
abstract: Patients with renal impairment have an increased risk for cardiovascular disease, which may be the result of advanced glycation end products (AGEs). The aim of this study was to investigate the levels of AGE peptides in relation to kidney function and to study the relationship of AGE peptides with endothelial function and inflammation in type 1 diabetic patients. We measured plasma levels of AGE peptides with a simple fluorescent analytical procedure in patients with end-stage renal disease with or without diabetes and in 60 type 1 diabetic patients categorized as having normo-, micro-, or macroalbuminuria. Using enzyme-linked immunosorbent assays, we determined vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin, plasminogen activator inhibitor 1 (PAI-1), tissue type-specific plasminogen activator (tPA), von Willebrand factor (vWF), and soluble thrombomodulin (sTM) to be markers of endothelial function and determined C-reactive protein (CRP) to be a marker of inflammation. AGE peptides were increased approximately fivefold in patients with end-stage renal disease, without difference between patients with or without diabetes. In type 1 diabetic patients, the increase of AGE peptides across the groups normo-, micro-, and macroalbuminuria (with medians [range] of 12.6% [7.8-27.2%], 12.1% [7.8-162%], and 46.5% [9.0-248.9%]) was associated with serum creatinine level and not with albumin excretion rate (AER). The relationship with serum creatinine decreased but remained significant after adjusting for age, sex, diabetes duration, hemoglobin A1c (HbA1c), AER, systolic and diastolic blood pressure (BP), and CRP in multiple linear-regression analysis. AGE peptide levels were significantly associated with sVCAM-1 and sTM, independently of serum creatinine. However, these relationships were no longer significant after adjusting for age, sex, diabetes duration, HbA1c, AER, systolic and diastolic BP, and CRP. This study shows that plasma levels of AGE peptides rise with renal impairment, as determined by serum creatinine. AGE peptides are associated with some markers of endothelial activation, which may suggest an involvement of AGE peptides in the acceleration of cardiovascular complications in type 1 diabetic patients with renal impairment.
authors.affiliation: Department of Clinical Chemistry, University Medical Center, Amsterdam, the Netherlands. C.Schalkwijk@INTMED.unimaas.nl
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Piet M
authors.initials: PM
authors.lastname: Ter Wee
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000419:Albuminuria; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000652:urine; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000628:therapy; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis; D017582:Renal Replacement Therapy; D012307:Risk Factors
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced