Serum Levels of Antibodies to Advanced Glycation End Products in Patients with Type 2 Diabetes Mellitus and Hypertension

Abstract

Background and Aims: Proteins containing advanced glycation end products are highly immunogenic and anti-advanced glycation end products antibodies (anti-AGEs antibodies) are found in the sera of diabetics. Materials and methods: Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of anti-advanced glycation end products antibodies in sera of 93 patients with type 2 diabetes mellitus and arterial hypertension (mean age 61.4±11.3 years, diabetes duration 9.88±3.12 years; hypertension duration 9.28±4.98). These values were compared to serum anti-AGEs antibodies in 42 age and sex matched controls. Diabetics were divided in two groups according to presence or absence of microangiopathy, group 1 (n=67) and group 2 (n=26), respectively. Results: Serum levels of anti-AGEs antibodies in patients with type 2 diabetes mellitus and arterial hypertension were statistically significantly higher than those in the control group (1.39±0.39 vs. 1.05±0.32), (p<0.05). Group 1 showed significantly higher levels of anti-AGEs antibodies than those of healthy controls (1.53±0.14 vs. 1.05±0.32), (p<0.01). Anti-AGEs antibodies levels were higher in patients with microvascular complications than these in patients without complications. Anti-AGEs antibodies correlate with diastolic blood pressure (r=0.26, p=0.05) and body mass index (r=0.37, p=0.03). We found significantly higher percentage of positive patients for anti-AGEs antibodies (mean+2SD) in group 1 than in group 2. Conclusion: Determining the levels of serum anti-AGEs antibodies can help physicians make early diagnosis and prognosis of the severity of late diabetic complications in hypertensive patients.

Aerobic Exercise Training Improves Microvascular Function and Oxidative Stress Parameters in Diet-Induced Type 2 Diabetic Mice

“…10 Further, Gu et al showed that the activity of key enzymes in AGE formation, concentration of highly reactive intermediates, expression of RAGE, oxidative stress, and inflammation in the aortas of aged rats could be reduced by physical training. [76][77][78] To date, few studies have examined the content of AGEs in WAT; to our knowledge, this is the first study to examine the AGE-RAGE axis in pre-clinical models of T2D. [79][80][81] Although we did not find significant differences in AGE-RAGE axis activation among the groups, we observed a positive correlation between AGE levels and microcirculatory changes in WAT, suggesting that AGEs could be involved in developing adipose tissue microcirculation dysfunction in T2D.…”

“… 7 , 10 Monitoring serum AGE levels has recently been reported to help in the early diagnosis of T2D and in predicting the severity of its late complications. 76 Therefore, the AGE-RAGE signaling pathway was examined in the liver of T2D mice to determine its involvement in the exercise-mediated improvement of microcirculation. T2D mice exhibited increased AGE-RAGE levels, which were negatively affected by aerobic exercise.…”

“… 10 Further, Gu et al showed that the activity of key enzymes in AGE formation, concentration of highly reactive intermediates, expression of RAGE, oxidative stress, and inflammation in the aortas of aged rats could be reduced by physical training. 76–78 …”

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression

“…The detection of elevated levels of autoantibodies to AGEs in patients with T2D raises the question of their role in the pathophysiology of the disease. Nikolov et al have found that serum levels of total anti-AGE antibodies were significantly higher in hypertensive patients with T2D with microvascular complications than healthy controls and patients without such complications [ 22 ]. Similar results have also been reported in patients with T1D [ 29 , 30 ].…”

“…Structural changes in biomolecules due to AGE modifications are associated with the formation of new epitopes that make them potential targets of the immune system. Anti-AGE antibodies that can be used as a biomarker for vascular damage have been found in the sera of patients with diabetes [ 4 , 21 , 22 , 23 ]. Due to their immunogenicity, AGEs can cause inflammation by stimulating the AGE receptor (RAGE), which triggers a series of signaling cascades and activates pro-inflammatory genes [ 24 , 25 , 26 ].…”