Oxidised Met ¹⁴⁷ of human serum albumin is a biomarker of oxidative stress, reflecting glycaemic fluctuations and hypoglycaemia in diabetes

Abstract

Oxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity. We used liquid chromatography-high resolution mass spectrometry (LC-MS) to show that oxidised and non-oxidised Met residues at position 147 of human serum albumin (Met ¹⁴⁷) can be accurately and reproducibly quantified with stable isotope-labelled peptides. Met ¹⁴⁷ oxidation was significantly higher in patients with diabetes than in controls. Least square multivariate analysis revealed that glycated haemoglobin (HbA _1c) and glycated albumin (GA) did not significantly influence Met ¹⁴⁷ oxidation, but the GA/HbA _1c ratio, which reflects glycaemic excursions, independently affected Met ¹⁴⁷ oxidation status. Continuous glucose monitoring revealed that Met ¹⁴⁷ oxidation strongly correlates with the standard deviation of sensor glucose concentrations and the time spent with hypoglycaemia or hyperglycaemia each day. Thus, glycaemic variability and hypoglycaemia in diabetes may be associated with greater oxidation of Met ¹⁴⁷. Renal function, high-density lipoprotein-cholesterol and serum bilirubin were also associated with the oxidation status of Met ¹⁴⁷. In conclusion, the quantification of oxidised and non-oxidised Met ¹⁴⁷ in serum albumin using our LC-MS methodology could be used to assess the degree of intravascular oxidative stress induced by hypoglycaemia and glycaemic fluctuations in diabetes.