Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study

Abstract

Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ≥ 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.

Progress of clinical evaluation for vascular aging in humans

“…At the same time, FMD is also an important assessment method of target organ injury. [7] baPWV is another main index to detect the degree of arteriosclerosis, and its change is the overall reflection of abnormal structure and function of arteries. The results showed that baPWV was an independent predictor of hypertension, and the risk ratio of baPWV increased by 1…”

Advanced glycation end product intake during pregnancy and offspring allergy outcomes: A Prospective cohort study

“…Previous studies have indicated that AGEs intake may be implicated in non-communicable diseases such as diabetes, 31,32 chronic kidney disease, 33 non-alcoholic fatty liver disease, 34 coronary heart disease, 32 obstructive airway diseases, 35 cancer, 36 dementia and aging, 37 arthritis, 38 asthma/wheeze 39,40 and chronic bronchitis. 37,[41][42][43] Studies focusing on allergy outcomes, showed an association between the childhood diet, studied at a similar time as allergic outcomes.…”

“…The discrepancy in findings between our study and previous studies may also be explained by different measures and methods used to determine AGEs intake or different methods for assessment of allergy outcomes. Previous studies investigating the association between AGEs and disease outcomes used serum levels of AGEs, 31,46 or activity of the age receptor (RAGE) 37,42,43 rather than dietary intake of AGEs as in our study. Some studies measured reported highfructose corn syrup-sweetened soft drinks, fruit drinks, 38 apple juice, and soda intake.…”

The role of diabetes in the onset and development of endothelial dysfunction

“…Накопление конечных продуктов гликирования при прогрессировании диабета способствует структурному ремоделированию сосудистой стенки, что проявляется, в частности, увеличением толщины интимы и медии сонных артерий [51].…”