Glycation is a non-enzymatic, post-translational modification of proteins which is elevated in several pathologies, notably diabetes. An early-stage glycation product, glycated hemoglobin (HbA1c), is used in the clinical management of diabetes, and advanced glycation end-products (AGEs) are implicated in the etiology of diabetic complications. Fingernail clippings contain a time-integrated repository of several metabolic processes during the preceding 3–5 months, are easily sampled, and various elements and molecules have been shown to remain stable within them for long periods without refrigeration.Building upon a few underexploited studies, we investigated fingernails as a non-invasive matrix to assess glycation using liquid chromatography–mass spectrometry to quantify ungual biomarkers of early- and advanced glycation (respectively furosine, as a fructose-lysine derivative, and two AGEs (Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL)). The method was appropriately validated and provided accurate and precise measurements of two amino acids and the glycation biomarkers. Sample storage at ± 25 °C for 12 months had no effect upon these analytes, and the method was applied to fingernails from 87 people with diabetes.There was a moderate, linear correlation between ungual furosine concentrations and HbA1c at the time of nail sampling (rs = 0.339, p = 0.0011). Among subjects for whom previous measurements were available, there was no correlation between ungual glycation and HbA1c measured > 3 months before nail sampling, indicating that ungual furosine reflects early-stage glycation over a similar period to HbA1c. This study provides further evidence, using modern analytical techniques, that fingernails offer the possibility to quantitatively and non-invasively assess glycation.
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