Assessment of oxidative stress and endothelial dysfunction in Asian Indians with type 2 diabetes mellitus with and without macroangiopathy.
BACKGROUND
Enhanced oxidative stress coupled with increased expression of adhesion molecules (e.g. VCAM-1, ICAM-1) and decreased nitric oxide (NO) levels are implicated in development of atheromatous vascular lesion in diabetes. The present study addresses the correlation between oxidative stress, vascular cell adhesion molecules-1 (VCAM-1), NO end products and macroangiopathic complications in type 2 diabetes mellitus (DM).


METHODS
The study population consisted of three groups (i) diabetic patients with macroangiopathy (Group I); (ii) diabetic patients without macroangiopathy (Group II) and (iii) healthy controls (Group III) (n = 30, each group).


RESULTS
Serum malondialdehyde(MDA) concentration was significantly higher in diabetic patients as compared to controls. Group I had significantly higher malondialdehyde level as compared to Group II (P < 0.05) (5.12 +/- 1.83 micromol/l vs. 4.22 +/- 1.03 micromol/l), suggesting higher oxidative stress in patients with macroangiopathy. Significant reduction in NO end products was observed in diabetic patients compared to controls. Levels of serum NO end products levels were further reduced in patients with macroangiopathy compared to those without macroangiopathy. Group I (971.67 +/- 230.13 ng/ml) and Group II (823.55 +/- 197.74 ng/ml) had significantly higher level of sVCAM-1 compared to healthy controls (541.14 +/- 118.25 ng/ml) (P < 0.001). Also, patients with macroangiopathy had significantly higher levels of sVCAM-1 compared to those without macroangiopathy (P < 0.05). Multiple regression analysis indicated that post-prandial blood glucose, GSH and MDA were independent predictors of sVCAM-1 level (R = 0.690, P = 0.000).


CONCLUSIONS
It can be concluded from the present study that an enhanced oxidative stress coupled with endothelial dysfunction as indicated by reduced activity of NO pathway and enhanced expression of sVCAM-1 play an important intermediary role in the pathogenesis of macrovascular complications in type 2 DM.
Singhania
N
N
Department of Biochemistry, University College of Medical Sciences, Shahdara, Delhi, India.
Puri
D
D
Madhu
S V
SV
Sharma
S B
SB
D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007194:India / Q000208:ethnology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000172:deficiency / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012044:Regression Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D008315:Malondialdehyde