Simple non-invasive assessment of advanced glycation endproduct accumulation

Abstract

Aims/hypothesis. The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. Methods. Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age-and sexmatched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N ε -(carboxymethyl)-lysine (CML) and N ε -(carboxyethyl)lysine (CEL).Results. Autofluorescence correlated with CLF, pentosidine, CML, and CEL (r=0.47-0.62, p≤0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA 1 c of the previous year and creatinine levels. Conclusions/interpretation. The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.

Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue

“…AGE-reader measurements AGE levels on the volar side in the forarm skin were measured with the AGE reader, a noninvasive, portable device, which has been comprehensively validated with AGEs measured in skin biopsies (Meerwaldt et al 2004), DiagnOptics BV, Groningen, the Netherlands. The AGE reader measurements were made after the main study due to the availability of the AGE reader equipment.…”

Elevated skin autofluorescence is strongly associated with foot ulcers in patients with diabetes: a cross-sectional, observational study of Chinese subjects

“…Skin AF was measured with an AGE reader (DiagnOptics BV, Groningen, the Netherlands), as previously described (Meerwaldt et al, 2004). The measurement steps were carried out in strict accordance with the product instructions.…”

“…This simple, non-invasive method was designed based on the fluorescent properties of AGEs. Their first clinical trial showed a positive correlation between collagen-linked fluorescence and AGEs content in skin biopsies (Meerwaldt et al, 2004;2005b). The assessment of skin AF has some advantages over traditional measurements of plasma AGEs (Dorrian et al, 1998), including being inexpensive, easy to conduct, non-invasive, with a more reproducibility and a higher correlation to tissue contents of AGEs (Monami et al, 2008).…”

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

“…Assessment of AGE accumulation in practice has been simplified by devices that measure skin autofluorescence (AF). AF allows for noninvasive assessment of tissue AGE deposition by exploiting the close correlation between collagen-linked fluorescence and AGE content observed in skin biopsies (13). Skin AF measurement has been validated against levels of specific AGE molecules in patients with diabetes and CKD and healthy controls (14)(15)(16)(17)(18).…”