TY - JOUR
T1 - Water T2 as an early, global and practical biomarker for metabolic syndrome
T2 - An observational cross-sectional study
AU - Robinson, Michelle D.
AU - Mishra, Ina
AU - Deodhar, Sneha
AU - Patel, Vipulkumar
AU - Gordon, Katrina V.
AU - Vintimilla, Raul
AU - Brown, Kim
AU - Johnson, Leigh
AU - O'Bryant, Sid
AU - Cistola, David P.
N1 - Funding Information:
This work was supported by institutional start-up funds (to D.P.C.) from the University of North Texas Health Science Center, Fort Worth and the Texas Tech University Health Sciences Center El Paso, as well as a grant from the Garvey Texas Foundation. The Health & Aging Brain Study, which provided some of the subjects and data for this study, is supported by NIA/NIH Grant R01AG039389 (to S.O.) and the UNT Health Science Center. Additional funding was received from the Hogg Foundation, the Institute for Aging and Alzheimer’s Disease Research and the Alzheimer’s Disease Center, University of Texas Southwestern Medical Center, Dallas.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/19
Y1 - 2017/12/19
N2 - Background: 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. 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. Methods: Water 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. Results: Plasma 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. Conclusions: Water 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.
AB - Background: 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. 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. Methods: Water 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. Results: Plasma 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. Conclusions: Water 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.
KW - Atherosclerosis, cardiovascular disease
KW - Inflammation, dyslipidemia, magnetic resonance relaxometry
KW - Insulin resistance
KW - Metabolic syndrome
KW - T, transverse relaxation time, type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85038391196&partnerID=8YFLogxK
U2 - 10.1186/s12967-017-1359-5
DO - 10.1186/s12967-017-1359-5
M3 - Article
C2 - 29258604
AN - SCOPUS:85038391196
SN - 1479-5876
VL - 15
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 258
ER -