Diabetes
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21709
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Browsing Diabetes by Author "Cistola, David"
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Item Plasma Water T2 as a Biomarker for Early Insulin Resistance Syndrome(2016-03-23) Robinson, Michelle; Deodhar, Sneha; Patel, Vipul; Cistola, David; Mishra, InaInsulin resistance is defined as a blunted response to insulin by tissues. It is thought to be the body's response to energy imbalance and is exacerbated by over-nutrition, physical inactivity, obesity and/or genetic factors. Early-stage insulin resistance does not occur in isolation, but is part of a broader syndrome that includes four main components: (1) compensatory hyperinsulinemia, (2) dyslipidemia, (3) subclinical inflammation with shifts in plasma protein levels, and (4) subclinical acid-base abnormalities. Individuals with insulin resistance are at higher risk for developing type 2 diabetes. Yet, insulin resistance is often undetected by the tests used to diagnose and screen for type 2 diabetes, namely fasting serum glucose and hemoglobin A1c. There is an unmet need for practical screening tools for early insulin resistance syndrome in order to preserve pancreatic function and prevent type 2 diabetes. Since water hydrogen bonds to virtually every protein and lipoprotein particle in the blood, we hypothesized that the mobility of water in plasma is sensitive to the subclinical shifts in proteins and lipoproteins that occur in early insulin resistance syndrome. Water mobility can be measured as plasma water T2 using a simple benchtop implementation of nuclear magnetic resonance. To test this hypothesis, we conducted an observational cross-sectional study of 51 asymptomatic, non-diabetic human subjects, ages 24-80, and quantified the association of plasma water T2 values with over 100 established metabolic biomarkers and diagnostic tests. Plasma water T2 exhibited bivariate correlations with markers of each of the four components of the insulin resistance syndrome. Multiple regression models revealed independent associations of plasma water T2 with fasting insulin levels, total serum protein concentration or viscosity, white blood cell or neutrophil count, and total cholesterol. Analysis using receiver operator characteristic curves demonstrated that plasma water T2 can diagnose insulin resistance (as defined by the McAuley Index) with a sensitivity of 86%. By comparison, the sensitivities of fasting glucose and hemoglobin A1c were 14 and 47%, respectively. This discovery provides a foundation for developing a new diagnostic test for early insulin resistance syndrome and a practical screening tool for the early identification of individuals at risk for type 2 diabetes.Item Whole Blood NMR Relaxometry for the Detection of Insulin Resistance(2016-03-23) Deodhar, Sneha; Mishra, Ina; Cistola, David; Patel, VipulkumarTime-domain nuclear magnetic resonance relaxometry (TD-NMR) is a practical method for measuring the physical and dynamical properties of complex, heterogeneous samples. In prior work, we showed that TD-NMR measurements of human plasma or serum report on an individual’s metabolic status, particularly with respect to insulin resistance. The relationship between plasma water transverse relaxation time (T2) and insulin resistance is mediated by subtle subclinical shifts in protein and lipoprotein levels in the circulation. The previous test required separation of blood cells in order to conduct T2 measurements on isolated plasma or serum. We hypothesized that this separation may not be required, as it is conceivable that similar metabolic relationships could be gleaned from T2 measurements on water in whole blood. To test this hypothesis, we conducted an observational, cross-sectional study of over 30 asymptomatic, non-diabetic human subjects who were recruited though an approved IRB protocol. Antecubital venous blood was drawn into lavender-top tubes containing EDTA as the anticoagulant. The blood samples, prior to NMR measurements, were allowed to spontaneously settle in the tube thereby creating two phases: a liquid supernatant (plasma) and blood cell pellet. The NMR relaxation constants T1 and T2 were determined using a Bruker mq20 Minispec NMR instrument operating at 20MHz. The data were collected using inversion recovery and modified Carr-Purcell-Meiboom-Gill pulse sequences, respectively. The NMR time-decay curves were transformed using an inverse-Laplace algorithm in order to extract T2 values. In addition, we measured over 100 diagnostic biomarkers on each subject and correlated the NMR measurements with established markers of metabolic function. The supernatant water T2 values from whole blood were compared to those obtained from fractionated plasma samples and to the other 100-plus biomarkers. The associations were quantified using parametric and non-paramertic correlations and the Student t-test. Statistically-significant bivariate correlations were observed between whole blood water T2 and and lipid biomarkers, which are associated with insulin resistance and metabloic disease.