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Higher Plasma Soluble Receptor for Advanced Glycation End Products (sRAGE) Levels Are Associated With Incident

Corneal complications are often associated with diabetes mellitus and can be vision threatening. As a result of AGE accumulation in the arterial wall, collagen fibers are crosslinked.4, 5, 6 In contrast to the physiological crosslinking of collagen (on N- and C-terminal ends only), AGE-mediated crosslinking increases the collagen content in the arterial wall (primarily because of its higher resistance to enzymatic proteolysis and decreased degradation rate), which is clinically manifested as an increased pulse wave velocity (PWV).6, 7 The community-based Baltimore Longitudinal Study of Ageing (493 participants) showed that elevated serum AGEs were independently associated with an increased PWV.8 A smaller study by McNulty et al.9 demonstrated the same association in 30 untreated hypertensive patients. However, the molecular mechanism for thrombogenic diathesis in diabetes is not fully elucidated. The aim of our current study is to investigate how non-cross-link and non-fluorescent Nɛ-carboxymethyl-Lysine (CML), a major immunogen of AGEs, affect the progression of atherosclerotic calcification in diabetes. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. In addition, inflammation may also reduce NO release because inflammatory cytokines like tumor necrosis factor-α have been shown to reduce the expression of endothelial NO synthase (eNOS) (5). CONCLUSIONS Higher levels of sRAGE are associated with incident fatal and nonfatal CVD and all-cause mortality in individuals with type 1 diabetes.

Among them, cernuoside was shown to be the most potent AGE inhibitor with an IC50 value of 21.21 μ mol/L. Exposure to lower temperatures with more moisture corresponded to lower levels of AGE as opposed to cooking with higher temperatures and lower moisture levels for equal weights. At the molecular level, RAGE is upregulated in atherosclerotic lesions in diabetes (2). With duration of diabetes, the AGE contents increased significantly both in renal cortex and aorta. The latter was significantly reduced by co-incubation with sRAGE (P < 0.01). Effects of incubation with G-6-P and aminoguanidine (AG) on glycation of ECM components. In addition, the extent to which any such associations could be explained by markers of endothelial and renal dysfunction, low-grade inflammation, arterial stiffness, and AGEs is also not known. We hereby address these questions in a 12-year prospective follow-up study.

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