Abstract
Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.
Highlights
Diabetic retinopathy (DR), which is a major vascular complication of diabetes mellitus (DM), has been recognized for decades, and disease progression often results in devastating visual loss [1]
Since non-invasively measured skin autofluorescence (sAF) can estimate the levels of advanced glycation end products (AGEs) accumulation, we examined the demographic differences and AGE scores measured by sAF in each DR stages and evaluated the clinical relevance of AGEs in patients with DM, especially those with proliferative diabetic retinopathy (PDR)
AGE scores were higher in patients with DM, and independently associated with progression of DR
Summary
Diabetic retinopathy (DR), which is a major vascular complication of diabetes mellitus (DM), has been recognized for decades, and disease progression often results in devastating visual loss [1]. Several previous studies have shown that hyperglycemia, smoking, hypertension, and other factors are related closely to diabetic angiopathy [2,3,4,5], these traditional factors do not fully explain the development of the vascular complications of DM and the involvement of other factors likely to promote this process. The accumulation of advanced glycation end products (AGEs) in tissues increases in DM. AGEs can modify the functional properties of intracellular proteins such as antioxidant enzymes, induce crosslinking of collagen leading to increased stiffness of the blood vessels, and interact with a receptor for AGEs (RAGE), which activate proinflammatory signaling pathways [6,7,8]. The relevance between AGEs levels and DR stages and the clinical utility of skin autofluorescence (sAF) measurements are largely unknown
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