A Clinical And Experimental Study On Advanced Glycation End Products And Arterial Stiffness

Part I.Association between skin or plasma advanced glycation end products and arterial stiffnessObjective We compared skin and plasma measurements of advanced glycation end products(AGEs),with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension.Methods Skin AGEs accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25.Plasma AGEs concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis.Arterial stiffness was assessed by carotid-femoral pulse wave velocity(PWV)using the Sphygmo Cor system(Sydney,Australia).Results The 218 participants(96 [44.0%] men,mean age 51.9 years)had a mean skin autofluorescence of 1.89 arbitrary units,plasma AGEs concentration of 4.47 μg/ml,and carotid-femoral PWV of 8.0 m/s.Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients(n=31,r=0.37,P=0.04)but not in subjects with normoglycemia(n=187,r=-0.05,P=0.48).Nonetheless,both measurements were significantly(P≤0.001)higher in men(2.00 arbitrary units and 6.73 μg/ml,respectively)than women(1.81 arbitrary units and 3.60 μg/ml,respectively)and in diabetic or prediabetic(2.03 arbitrary units and 6.61 μg/ml,respectively)than normoglycemia subjects(1.87 arbitrary units and 4.17 μg/ml,respectively),but similar in hypertensive(n=105)and normotensive subjects(n=113,P≥0.35).In adjusted multiple regression analyses,plasma AGEs concentration was significantly associated with PWV in all subjects(β 0.44 m/s for each 10-time increase;P=0.04)and in subgroups of men and diabetes and prediabetes(β 0.51 to 3.01 m/s for each 10-time increase;P≤0.02).Conclusions In conclusion,although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes,they might measure something different and have different clinical relevance,such as for arterial stiffness.Part II.Effects of high-fat diet and high-fructose beverage on plasma advanced glycation end products in ratsObjective Our previous study showed that plasma AGEs concentration was higher in the presence of diabetes or prediabetes and with higher total cholesterol/HDL ratio.In the present experiment,we investigated effects of highfat diet and high-fructose beverage on plasma advanced glycation end products in rats.Methods After one week adaptive feed,48 Sprague Dawley(SD)male rats were randomly divided into four groups: A normal diet,B high-fructose beverage(12%),C high-fat diet,and a combination of high-fat and high-fructose diet.All rats were fed with for 12 weeks.Dietary intake and body weight were measured every other week.Blood pressure on the tail artery was measured 3 times consecutively at week 0,6 and 12.Blood and urine were sampled at 6 and 12 weeks for measurements of plasma glucose,serum lipids,plasma AGEs,and serum uric acid and for measurement of urinary albuminuria excretion.Results Although food intake did not change with time,body weight increased significantly(P<0.0001)in all four groups,with the greatest growth in group C to an average of 605 g at week 12(P<0.05,versus groups A,B,and D).Plasma glucose concentration was similar in all four groups at week 6,but was significantly higher in groups B,C and D than group A at week 12.Serum lipids differed between the four groups,with higher levels of serum triglycerides and total and LDL cholesterol and lower levels of HDL cholesterol in groups B,C,and D than group A,with a greater difference at week 12.Plasma AGEs concentration significantly(P≤0.003)increased from 6 to 12 weeks in groups B(21.1 to 49.3 mg/m L),C(28.5 to 50.5 mg/m L)and D(33.6 to 52.4 mg/m L),but not in group A(34.5 to 45.6 mg/m L P=0.23).Urinary albumin excretion also significantly increased from 6 to 12 weeks in groups B(342.1 to 412.4 mg/m L),C(351.2 to 399.9 mg/m L),and D(350.5 to 415.5 mg/m L)and serum uric acid in group D(90.9 to 103.4 μmol/L),but not in group A(329.2 to 327.0 mg/m L,P=0.90),with significant differences between groups B,C and D and group A at 12 weeks(P≤0.02).Further analysis showed that the change in plasma AGEs concentration from 6 to 12 weeks were significantly correlated with the changes in plasma glucose concentration(r=0.44,P=0.004)and serum HDL concentration(r=-0.33,P=0.04).Conclusions Plasma AGEs concentration increased with age advancing.High-fat diet and high-fructose beverage significantly increased plasma AGEs and serum uric acid and urinary albuminuria excretion.