Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study

Abstract

BackgroundMetabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement.MethodsWater T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression.ResultsPlasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma.ConclusionsWater T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual’s metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1359-5) contains supplementary material, which is available to authorized users.

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

“…al. , recently found that the baseline T 2 of water plasma/serum shown a strong correlation in subjects with metabolic abnormalities 38, 48 . Interestingly, ROC analysis indicates DM subjects with good-glycemic control and healthy controls subjects had AUC of 0.91, much higher than the one observed in RBCs (AUC<0.67) (Figure 5C).…”

“…Water is an attractive natural molecular network probing system as it forms hydrogen bonds with practically all others macromolecule ( e.g. , protein, metabolite) that are present in human circulation 37, 38 . Therefore, a subtle change of the molecular environment can induce a measurable change in the proton relaxation rate.…”

Aptamer-based search for correlates of plasma and serum water T2: implications for early metabolic dysregulation and metabolic syndrome

“…In an observational cross-sectional study of 72 non-diabetic human subjects, we discovered that plasma and serum water T 2 detect MetS-associated abnormalities with high sensitivity and specificity [ 8 ]. Measured using benchtop nuclear magnetic resonance relaxometry [ 9 ], T 2 refers to the time constant for the decay or “relaxation” of the transverse component of the NMR signal.…”

“…One example is the shifts that occur with an acute phase response, which increase the levels of some globulins, while decreasing albumin. As globulins are higher molecular weight than albumin, the net effect is to slow the rotational mobility of bound water and decrease water T 2 [ 8 , 9 ].…”

“…Fasting hyperinsulinemia (insulin resistance), dyslipidemia and inflammation each have independent and additive contributions to the lowering of water T 2 [ 8 ]. Hence, water T 2 captures a global view of an individual’s metabolic health status with just one measurement.…”