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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number258
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
StatePublished - 19 Dec 2017

Fingerprint

Biomarkers
Cross-Sectional Studies
Water
Medical problems
Plasmas
Insulin
Inflammation
Type 2 Diabetes Mellitus
Insulin Resistance
Fasting
Atherosclerosis
Screening
Blood
Water-Electrolyte Balance
Blood Coagulation Factors
Acute-Phase Proteins
R Factors
Hyperinsulinism
Proteome
Dyslipidemias

Keywords

  • Atherosclerosis, cardiovascular disease
  • Inflammation, dyslipidemia, magnetic resonance relaxometry
  • Insulin resistance
  • Metabolic syndrome
  • T, transverse relaxation time, type 2 diabetes mellitus

Cite this

Robinson, M. D., Mishra, I., Deodhar, S., Patel, V., Gordon, K. V., Vintimilla, R., ... Cistola, D. P. (2017). Water T2 as an early, global and practical biomarker for metabolic syndrome: An observational cross-sectional study. Journal of Translational Medicine, 15(1), [258]. https://doi.org/10.1186/s12967-017-1359-5
Robinson, Michelle D. ; Mishra, Ina ; Deodhar, Sneha ; Patel, Vipulkumar ; Gordon, Katrina V. ; Vintimilla, Raul ; Brown, Kim ; Johnson, Leigh ; O'Bryant, Sid ; Cistola, David P. / Water T2 as an early, global and practical biomarker for metabolic syndrome : An observational cross-sectional study. In: Journal of Translational Medicine. 2017 ; Vol. 15, No. 1.
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Water T2 as an early, global and practical biomarker for metabolic syndrome : An observational cross-sectional study. / Robinson, Michelle D.; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V.; Vintimilla, Raul; Brown, Kim; Johnson, Leigh; O'Bryant, Sid; Cistola, David P.

In: Journal of Translational Medicine, Vol. 15, No. 1, 258, 19.12.2017.

Research output: Contribution to journalArticle

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.

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

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