WHOLE BLOOD T2P LINKS HEMOGLOBIN STATUS TO CARDIOMETABOLIC HEALTH

Abstract

Therapeutic Area: Diabetes Background: Plasma water T2 is an early, global and practical biomarker of cardiometabolic health. It is measured by compact magnetic resonance relaxometry using separated human plasma. A prior goal was to determine whether plasma water T2 could be estimated using unseparated whole blood. Settled, EDTA-anticoagulated whole blood yields two T2 values: T2S for the plasma supernatant and T2P for the blood cell pellet. Whole blood T2P measures the properties of water inside red blood cells and monitors the oxygenation and oxidation states of hemoglobin. Here we investigated the independent and mediating role of T2P with markers of cardiometabolic health. Methods: This was an observational, cross-sectional biomarker discovery study of 43 asymptomatic disease-free adults, ages 23-61, of varying race/ethnicity, 47% female. Each participant underwent a medical history & physical exam and was metabolically phenotyped using >130 biomarkers or clinical lab tests. Whole blood T2P values were recorded using a Bruker mq20 benchtop relaxometer and resolved using the discrete inverse Laplace transform algorithm in XpFIT (SoftScientific, Alango, Ltd.). The association of T2P with candidate predictors was explored using JMP Pro v16.2 (SAS Institute, Inc.). Machine-learning predictor screening was followed by multi-variable linear regression, along with correlation, latent-factor and mediation analyses. The effect size was standardized beta coefficient with 95% confidence interval (CI). Results: The strongest predictor of T2P was a latent variable incorporating markers of hyperinsulinemia, oxidative stress, inflammation, adiposity, dyslipidemia and hypoxia: β = -10.5, 95% CI: -15.4,-5.7, p<0.0001. Preliminary mediation analysis provided evidence that whole blood T2P (hemoglobin deoxygenation and/or oxidation) is a full mediator for the association between fasting insulin and markers of hypoxia (lactate) and chronic inflammation (IgG). Conclusions: A missing link between non-optimal cardiometabolic health and insidious cell/tissue damage may be a subclinical impairment in hemoglobin's ability to deliver oxygen. To pinpoint the impairment, whole blood T2P and metabolic markers are being compared with hemoglobin parameters from blood gas analysis of asymptomatic disease-free adults. As whole blood T2P can be measured using a fingerstick drop of blood and a miniaturized low-cost magnetic resonance device, it shows promise for cardiometabolic health screening at the point of care.