n(6)-(1-carboxyethyl)lysine and Diabetes-Mellitus--Type-1

We investigated the associations of pulse pressure (a measure of arterial stiffness) with the early glycation products hemoglobin A1c (HbA1c) and Amadori albumin and the advanced glycation end products pentosidine, Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine in a large group of type 1 diabetic individuals of the EURODIAB Prospective Complications Study. We did a cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 543 (278 men) European individuals with type 1 diabetes diagnosed at <36 years of age. We used linear regression analyses to investigate the association of pulse pressure with glycation products. Pulse pressure was significantly associated with plasma levels of Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine but not with HbA1c, Amadori albumin, and urinary levels of pentosidine. Regression coefficients adjusted for age, sex, mean arterial pressure, and duration of diabetes were 0.09 mm Hg (P=0.003) per 1 microM/M lysine Nepsilon-(carboxymethyl)lysine; 0.24 mm Hg (P=0.001) and -0.03 mm Hg (P=0.62) per 1 microM/M lysine Nepsilon-(carboxyethyl)lysine (in individuals with and without complications, respectively; P interaction=0.002); and 0.50 mm Hg (P=0.16) per 1% HbA1c; 0.07 mm Hg (P=0.12) per 1 U/mL Amadori albumin; and 0.77 mm Hg (P=0.48) per 1 nmol/mmol creatinine pentosidine. In young type 1 diabetic individuals, arterial stiffness is strongly associated with the advanced glycation end products Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine. These findings suggest that the formation of advanced glycation end products is an important pathway in the development of arterial stiffness in young type 1 diabetic individuals.

Topics: Adult; Blood Pressure; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Linear Models; Lysine; Male; Middle Aged; Multicenter Studies as Topic; Platelet Activating Factor; Prospective Studies

Diabetic and non-diabetic patients with renal failure have an increased risk for cardiovascular disease, which may be the result of uraemic toxins, including advanced glycation end-products (AGEs). The aim of the study was to investigate the levels of well-characterized AGEs, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) in relation to kidney function and to study the relationship of these AGEs to endothelial function and inflammation in type 1 diabetic patients.. Plasma levels of CML and CEL were measured in 60 type 1 diabetic patients categorized as having normal glomerular filtration rate (GFR) (>80 ml/min, n = 31) or decreased GFR (<80 ml/min, n = 29) as estimated by the Cockcroft-Gault formula. To assess the relationship of these AGEs to endothelial function and inflammation, markers of endothelial function von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), tissue type-specific plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP), a marker of inflammatory activity, were determined by enzyme-linked immunosorbent assays.. Plasma levels of CML and CEL were increased in diabetic patients with decreased GFR as compared with patients with normal GFR [CML 4.9 (2-12.6) vs 2.9 (1.7-4.4) micromol/l, P<0.000; and CEL 1.7 (0.9-3.3) vs 1.2 (1.7-4.4) micromol/l, P = 0.004, respectively). Independently of the GFR, the plasma levels of CML and CEL were significantly associated with sVCAM-1, vWf and sTM.. Plasma levels of CML and CEL rise with deterioration of GFR. Furthermore, CML and CEL levels are associated with markers of endothelial activation independently of renal function. This suggests an involvement of these AGEs in the acceleration of cardiovascular complications in patients with renal impairment.

Topics: Adult; Aged; Blood Coagulation Factors; C-Reactive Protein; Case-Control Studies; Diabetes Mellitus, Type 1; E-Selectin; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Kidney; Lysine; Male; Middle Aged; Thrombomodulin; Vascular Cell Adhesion Molecule-1