Skin autofluorescence is associated with microvascular complications in type 2 diabetes

Abstract

Background and aims: Skin autofluorescence (AF) is a marker of advanced glycation endproduct (AGE) accumulation in the body. AGEs are molecules formed through the non-enzymatic reactions of reducing sugars with proteins, lipids and nucleic acids. They accumulate at a constant but slow rate in the normal body. With increased glucose availability in diabetes, their formation is accelerated, and their deleterious effects on proteins have been implicated in diabetic complications. Upon excitation at 370 nm, AGEs have an emission spectrum at 440 nm, which is quantifiable as skin AF. This cross-sectional study investigated the relationship between skin AF and microvascular complications in Chinese type 2 diabetic subjects. Material and methods: Subjects were recruited from the diabetic complication assessment program of our hospital. Skin AF was measured over the volar surface of the forearms using the AGE Reader. Three measurements were taken over each forearm according to the manufacturer's instructions, and the skin AF, in arbitrary units (AU), was recorded as the average of the three measurements on each side. To adjust for the effect of skin pigmentation, which absorbs light and thus influences skin AF, the AGE Reader automatically compared skin reflectance measurements across the 300 to 420 nm range with those of a white Teflon block, which was assumed to have 100% reflectance. Anthropometric and biochemical data includingbody height and weight, blood pressure, fasting glucose and lipids and HbA1c were collected. Statistical analysis was performed with SPSS 19.0. Results: Skin AF was measured in 322 Chinese type 2 diabetic subjects (192 male, 130 female, 63.9+/-11.0 years), of which 229 had one or more microvascular complication(s). The median DM duration was 10 years (interquartile range 6-15 years) and the mean HbA1c was 7.84+/-1.35%. Skin AF correlated positively with age (r=0.350, p<0.001), DM duration (r=0.256, p<0.001), serum creatinine (r=0.280, p<0.001) and smoking pack-years (r=0.287, p=0.006), but not HbA1c (p=0.306). There was no gender difference in skin AF (p=0.73). Subjects with any microvascular complication had higher skin AF than those without (2.41+/-0.48 AU vs. 2.17 +/- 0.37 AU, p<0.001). Skin AF was higher in subjects with retinopathy (2.41+/-0.46 AU vs. 2.26 +/-0.45 AU, p=0.006), nephropathy (2.49+/-0.49 AU vs. 2.20+/-3.98 AU, p<0.001) and neuropathy (2.56+/-0.51 AU vs. 2.27+/-0.42 AU, p<0.001) compared to those without the respective complication. Skin AF was independently associated with nephropathy (OR for one AU increase in AF 2.65 [1.42-4.95]; p=0.002) and neuropathy (OR for one AU increase in AF 2.28 [1.15-4.54]; p=0.019) after adjusting for gender, age, smoking status and DM duration. The optimal skin AF cut-off value for having any microvascular complication, nephropathy and neuropathy were 2.263 AU (sensitivity 59.8%, specificity 63.6%), 2.263 AU (sensitivity 68.8%, specificity 62.0%) and 2.307 (sensitivity 70.1%, specificity 57.6%) respectively on ROC analysis. Conclusion: Skin AF was associated with diabetic complications, in particular nephropathy and neuropathy, in Chinese type 2 diabetic subjects. The AGE Reader might serve as a simple and non-invasive method to evaluate the risk of diabetic microvascular complication.