Skin AGEs and diabetic neuropathy

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Main idea: Skin autofluorescence represents a non-invasive, inexpensive, highly reproducible method of measuring AGEs. Increased skin AGEs have been linked with microvascular complications of diabetic neuropathy. In retinopathy, some correlation has been shown between AGEs and the progression of this complication. Additionally, skin AGEs are being increasingly appreciated as predictors of nephropathy. They appear to become increased before the impairment of nerve conduction parameters, the onset of symptoms, or an increase in vibration perception threshold.

Abstract: Skin autofluorescence represents a non-invasive, inexpensive, highly reproducible method of measuring AGEs. Increased skin AGEs have been linked with microvascular complications of diabetic neuropathy. In retinopathy, some correlation has been shown between AGEs and the progression of this complication. Additionally, skin AGEs are being increasingly appreciated as predictors of nephropathy. They appear to become increased before the impairment of nerve conduction parameters, the onset of symptoms, or an increase in vibration perception threshold. Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for the measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast, and simple method of skin autofluorescence (sAF) has recently gained special interest by its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy, and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The present review aims to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify their role and provide data on patient selection and cost-effectiveness.

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