Introduction: Advanced glycation end-products (AGEs) are known to play an important role in the pathogenesis of diabetic complications. Skin autofluorescence (AF), a marker of AGE accumulation in tissue, can be measured noninvasively using a skin AF reader. The present study aimed to evaluate the relationships of skin AF with diabetic microvascular complications and carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, in Japanese subjects with type 2 diabetes (T2D).
Methods: One hundred sixty-two subjects with T2D and 42 nondiabetic control subjects attending the outpatient clinic were examined. Skin AF and carotid max-IMT were measured using an AGE Reader™ and ultrasonography, respectively. Nephropathy was classified into five stages based on the urinary albumin-to-creatinine ratio (UACR) as follows: (1) pre-nephropathy (stage 1) (UACR < 30 mg/g Cr); (2) incipient nephropathy (stage 2) (30 ≤ UACR < 300 mg/g Cr); (3) overt nephropathy (stage 3) (UACR ≥ 300 mg/g Cr); (4) kidney failure (stage 4) (estimated glomerular filtration rate (eGFR) < 30 ml/min/1.732); and (5) dialysis therapy (stage 5). Patients with kidney failure and those receiving dialysis therapy were excluded because the sample size was too small. Retinopathy was diagnosed as nondiabetic retinopathy (NDR), nonproliferative retinopathy (NPDR), or proliferative retinopathy (PDR). Diabetic peripheral neuropathy (DPN) was diagnosed if two or more of the following were present: neuropathic symptoms (decreased sensation, positive neuropathic sensory symptoms), symmetric decreased distal sensation, and unequivocally decreased or absent ankle reflexes.
Results: Skin AF values were significantly higher in subjects with T2D (2.53 ± 0.45 AU) than in nondiabetic subjects (2.19 ± 0.34 AU, p < 0.001). Skin AF significantly increased with the severity of DPN (2.39 ± 0.37 with DPN vs 2.80 ± 0.48 without DPN, p < 0.001), retinopathy (NDR 2.42 ± 0.45, mild and moderate NPDR 2.64 ± 0.42, p = 0.042, severe NPDR and PDR 2.85 ± 0.35, p < 0.001), and nephropathy (pre-nephropathy 2.42 ± 0.44, incipient nephropathy 2.62 ± 0.45, p = 0.049, overt nephropathy 2.59 ± 0.46, p = 0.80). Skin AF was an independent determinant of the presence of DPN (OR 8.49, 95% CI 2.04-44.32, p = 0.006) and retinopathy (OR 3.73, 95% CI 1.20-12.90, p = 0.028) but not of diabetic nephropathy after correcting for confounding factors. In addition, skin AF (β = 0.170, p = 0.029) was an independent determinant of max-IMT, as was age (β = 0.436, p < 0.0001), after adjusting for other risk factors.
Conclusion: Skin AF as measured using an AGE Reader is a noninvasive surrogate marker for diabetic microvascular complications and early-stage atherosclerosis.
Keywords: Atherosclerosis; Diabetic microvascular complications; Intima–media thickness; Skin autofluorescence; Type 2 diabetes.