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

Michelle D Robinson,Kim Brown,Leigh Johnson,Ina Mishra,Raul Vintimilla,Sneha Deodhar,Vipulkumar Patel,David P Cistola,Katrina V Gordon,Sid O’Bryant

doi:10.1186/s12967-017-1359-5

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.

Highlights

Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease
Called insulin resistance syndrome or syndrome X, MetS can be defined in two ways [4,5,6]: (i) generally, as a constellation of abnormalities that includes insulin resistance, glucose intolerance, abdominal obesity, elevated blood pressure, dyslipidemia, and/or a pro-inflammatory, prothrombotic state, and (ii) as a set of clinical criteria and cutoffs
With respect to glucose markers, 47 of the 72 subjects were normoglycemic by American Diabetes Association criteria [40], with both fasting glucose < 100 mg/dL and H bA1c < 5.7%

Summary

Introduction

Metabolic 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. 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. The concepts are sound, but questions remain about how best to capture the heterogeneity of MetS, the subtypes, stages and unmeasured or residual risk factors [5]

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Results

Conclusion