Advanced Glycation End Products and Antioxidant Status in Type 2 Diabetic Patients With and Without Peripheral artery disease Annunziata Lapolla; Francesco Piarulli; Giovanni Sartore; Antonio Ceriello; et al Diabetes Care, 2007, vol 30 R2 황연희

INTRODUCTION Diabetes : risk factor of cardiovascular disease 1. Hyperglycemia and increased oxidative stress 2. Antioxidant defenses reduction in diabetes

AGEs : formation of abnormal cross-links in collagen  vascular stiffening : modification of lipoprotein( glycation)  foam cell formation : accumulate in coronary atherosclerotic plaques and cardiac tissue of diabetic patients Pentosidine (a marker of glycoxidation) : increased carotid intima-media wall thickness, arterial stiffening

Oxidative stress  protein & lipid peroxidation oxidized low density lipoprotein (oxLDL) are important events in the progression of atherosclerosis in diabetes mellitus Malondialdehyde (MDA) (an indicator of lipid peroxidation and oxidative stress in vivo) : elevated in diabetic patients with macroangiopathy Antioxidant defenses : Total reactive anti-oxidant potentials (TRAPs), vitamin E

Peripheral artery disease (PAD) : strong predictor of coronary and carotid atherosclerosis  Purpose : Relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD)

RESEARCH DESIGN AND METHODS 99 type 2 diabetic patients with and without PAD Control group : 20 subjects (10 men and 10 women) AGEs, pentosidine, MDA, TRAP, and vitamin E Coronary heart disease Cerebral vasculopathy Hypertension A physical examination and ophthalmoscopy ABI values

RESULT ABI values : 33 individuals with PAD (ABI ≤0.9) : the characteristic below-the-knee macroangiopathy, without media calcification : 66 patients without PAD (ABI >0.9)

By using linear regression analysis FBG A1C AGEs, MDA Pentosidine No-correlation ABICholesterol TG No-correlation AGEsInversely correlation all patients (slope = , r = , P < 0.001) with PAD (slope = , r = , P < 0.001) without PAD (slope = , r = , P < 0.001) pentosidineInversely correlation all patients (slope = , r = , P < 0.001) with PAD (slope = , r = , P < 0.001) without PAD (slope = , r = , P < 0.001) MDAInversely correlation only in patients with PAD (slope = , r = , P < 0.001) TRAPs Vit. E Correlation In patients with PAD (slope = , r = , P < 0.05)

Figure 1-Correlations between ABI and serum AGEs (A) and between ABI and serum pentosidine (B) in diabetic patients with PAD. with PAD (slope = , r = , P < 0.001) with PAD (slope = , r = , P < 0.001)

By a multiple regression model ABIAGEs & Pentosidine correlation in both patients with PAD (r = , P < ) without PAD (r = , P < 0.001) no significance in healthy control subjects TRAP, vitamin E, and MDA with PAD, a significant regression (r = , P < 0.001) TRAP, vitamin Eno significant regression coefficient  by a single linear regression between MDA and ABI.

DISCUSSION AGEs, pentosidine, and MDA : highly significant increased levels in patients with PAD AGEs and pentosidine : correlation with ABI in all diabetic patients : glyco-oxidation contributes to the development of atherosclerosis in the below-the-knee peripheral artery tree in type 2 diabetes. : more precisely strongly association pentosidine  may be a predictor of PAD in diabetes

MDA (lipid oxidation) : association with peripheral diabetic angiopathy TRAP and vitamin E (a defense mechanism against glycolipid oxidation) : were lower in type 2 diabetic patients with PAD : positively correlation with ABI in patients with PAD : not correlation with AGEs or pentosidine.

Rimm EB, Stampfer MJ : decreased levels of antioxidants favor cardiovascular disease Jones AF, Strain J : conflicting results of anti-oxidant status in type 2 diabetes TRAP : Only inversely correlation with MDA not AGEs  failed defensive role of antioxidants in the presence of the already developed vascular damage in type 2 diabetic patients  the inefficacy of treatment with antioxidants in 2ndary prevention

CONCLUSION In type 2 diabetic patients, glyco-oxidation, lipid oxidation (pentosidine and MDA) : strong association with below-the-knee diabetic macroangiopathy. Serum antioxidant capacity (TRAPs) : association with MDA (lipid oxidation) : not with AGEs  cannot prevent the development of PAD caused by AGEs