Diabetes and mass spectrometry

Abstract

Mass spectrometry (MS) has been successfully employed to investigate non-enzymatic protein glycation, a process relevant in diabetic disease. The high sensitivity and specificity of this technique allowed the development of methods that can individuate and evaluate some glycation markers to be validly employed in monitoring diabetes. More recent mass spectrometric techniques, such as the matrix-assisted laser desorption/ionization (MALDI), are able to determine the molecular weight of intact proteins. They were first employed in studying the in vitro reaction between hexoses and different proteins. Once the validity of the results obtained by this analytical approach was confirmed, a series of investigations on plasma proteins were undertaken in healthy and diabetic subjects. The method led to the evaluation of the number of glucose molecules condensed on the protein being studied, and consequently can be validly used for an accurate follow-up of metabolic control in diabetic patients. When applied to studies on haemoglobin glycation, the method showed that both alpha- and beta-globins are glycated to a similar extent and that the simply glycated molecules are accompanied by glyco-oxidized species therefore giving information on the oxidative stress experimented on in the subject. Furthermore, in the case of immunoglobulins, MALDI/MS was able to determine not only the total glycation level of IgG, but also to establish that the fragment antigen binding (Fab) moiety is the most glycated one, thus suggesting that the possible immunological impairment sometimes invoked in diabetes is related to the inhibition of the process of molecular recognition between antibody and antigen.