Relationship of glycation, antioxidant status and oxidative stress to vascular endothelial damage in diabetes.
OBJECTIVE
To examine the inter-relationships of various microvascular pathogenic mechanisms in diabetic patients.


METHODS
Patients with diabetes (n = 18) and non-diabetic subjects (n = 18) were studied.


RESULTS
Blood markers of glycaemic control and glycation differed between the two groups (glucose 10.9 +/- 7.6 vs. 4.7 +/- 0.63 mmol/l, p < 0.01; HbA1c 7.0 +/- 1.3 vs. 4.5 +/- 0.3%, p < 0.001; glycated LDL 8.8 +/- 2.5 vs. 6.1 +/- 1.2%, p < 0.001) but plasma antioxidant status did not. LDL oxidation resistance, measured as lag time to maximum oxidation initiated by copper ions, was decreased in diabetes (58. +/- 14.3 vs. 76.3 +/- 21.5 min, p < 0.01). Both soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), markers of endothelial dysfunction, were significantly higher in diabetes (ICAM 491 +/- 128 vs. 403 +/- 131 micro g/l, p < 0.05; VCAM 546 +/- 157 vs. 393 +/- 106 micro g/l, p < 0.01). Linear correlations were significant between HbA1c and lag time of LDL oxidation (r = -0.39, p < 0.05), ICAM (r = 0.40, p < 0.05) and VCAM (r = 0.38, p < 0.05). LDL oxidizability correlated with vitamin C (r = 0.51, p < 0.01) but not any adhesion molecule. In multivariate analysis, both ICAM and VCAM correlated with HbA1c only (r(2) = 0.16, F = 6.3, p < 0.01; r(2) = 0.14, F = 5.4, p < 0.01 respectively).


CONCLUSIONS
In diabetes, glycation, tissue oxidation and endothelial function are all abnormal and predisposing to microvascular complications but interrelationships are complex with glycation appearing most direct.
Wen
Y
Y
School of Health Sciences, University of Wolverhampton, Wolverhampton, UK.
Skidmore
J C
JC
Porter-Turner
M M
MM
Rea
C A
CA
Khokher
M A
MA
Singh
B M
BM
D000328:Adult; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*
D000975:Antioxidants; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL