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.
School of Health Sciences, University of Wolverhampton, Wolverhampton, UK.
Y
Y
Wen
J C
JC
Skidmore
M M
MM
Porter-Turner
C A
CA
Rea
M A
MA
Khokher
B M
BM
Singh
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