Molecular Phenotyping of Oxidative Stress in Diabetes Mellitus with Point-of-care NMR system

Abstract

Diabetes mellitus is one of the fastest growing health burdens globally. Oxidative stress which has been implicated to the pathogenesis of diabetes complication (e.g., cardiovascular event) were, however, poorly understood. We report a novel approach to rapidly manipulate the redox chemistry (in a single drop) of blood using point-of-care NMR system. We exploit the fact that oxidative stress changes the subtle molecular motion of water-proton in the blood, and thus inducing a measurable shift in magnetic resonance relaxation properties. This technique is label-free and the whole assays finish in a few minutes. Various redox states of the hemoglobin were mapped out using our newly proposed two-dimensional map, known as T1-T2 magnetic state diagram. We demonstrated the clinical utilities of this technique to rapidly sub-stratify diabetes subjects based on their oxidative status (in conjunction to the traditional glycemic level), to improve the patient risk stratification and thus the overall outcome of clinical diabetes care and management. (155 words) Key Points for SummariesO_LIA novel approach to rapidly manipulate the redox chemistry (in a single drop) of blood using point-of-care NMR system. C_LIO_LIAssessment of the oxidative status, in conjunction to their glycemic level allows sub-stratification of diabetes subjects which was demonstrated clinically. C_LI Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/565325v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@123d111org.highwire.dtl.DTLVardef@72e4e9org.highwire.dtl.DTLVardef@112b9bforg.highwire.dtl.DTLVardef@60e498_HPS_FORMAT_FIGEXP M_FIG C_FIG