Methods and tools for diagnosing insulin resistance and assessing health status using nmr relaxation times for water

Abstract

The subject invention pertains to a method that involves at least three steps: (1) acquisition of a NMR data set or spin relaxation curve for plasma, serum or whole blood samples, or for tissues monitored from outside the body, (2) analysis of the NMR data or relaxation curve to extract the T 2 and/or T 1 relaxation times for water (or surrogates thereof), and (3) conversion of the water T 2 and/or T 1 values (or surrogates thereof) into a measure of someone's health status (referred to as a T 2 or T 1 health score depending on the value (T 1 or T 2 or both T 1 and T 2 ) associated with the score). The T 1 and/or T 2 health score utilizes a statistical database derived from previous studies of subjects ranging from normal, healthy individuals to those having varying degrees of hidden or non-hidden metabolic abnormalities, such as inflammation, insulin resistance, lipid abnormalities (dyslipidemia), oxidative stress, brain abnormalities, cognitive impairment or other disorders, and provides a measure of a subject's overall metabolic and brain health status.

1 - 49 . (canceled) 
     
     
         50 . A method for determining the T 2  and/or T 1  health score of a subject comprising obtaining a NMR data set or spin relaxation curve for a sample with an NMR or MRI instrument tuned to measure a particular nucleus selected from  1 H,  2 H,  3 H or  17 O, analyzing the data or curve to extract T 2  and/or T 1  relaxation times for water or surrogates thereof and converting the water T 2  and/or T 1  values into a measure of the health status of the subject (the T 2  and/or T 1  health score). 
     
     
         51 . The method according to  claim 50 , wherein the sample is a plasma sample, a serum sample, whole blood sample, a tissue sample or a subject, such as a human being. 
     
     
         52 . The method according to  claim 50 , wherein the method comprises a step of partially suppressing the water signal, for example with a 180-degree inversion pulse followed by a delay or any other suitable method for partial suppression of the water signal prior to recording the relaxation curve. 
     
     
         53 . The method according to  claim 52 , wherein the delay time is tuned to eliminate radiation damping while maximizing water signal intensity. 
     
     
         54 . The method according to  claim 50 , wherein the step of analyzing the exponentially decaying or recovering NMR signal comprises acquiring the relaxation curve and subjecting the data to exponential analysis, for example transforming the data with an inverse Laplace transformation, or using any other suitable exponential analysis algorithm. 
     
     
         55 . The method according to  claim 54 , wherein said exponential analysis comprises the analysis of one or more exponential terms, for example one to six exponential terms, two to four exponential terms or three exponential terms. 
     
     
         56 . The method according to  claim 52 , wherein data acquisition begins about 1 to about 50 milliseconds after the start of pulse scheme that acquires the relaxation decay curve; about 16 to about 20 milliseconds after the start of the pulse scheme; or about 19 milliseconds after the start of the pulse scheme 
     
     
         57 . The method according to  claim 50 , wherein said sample is scanned multiple times. 
     
     
         58 . The method according to  claim 50 , wherein the step of converting the T 2  and/or T 1  values into a measure of the health status of the subject comprises comparing the T 2  and/or T 1  values obtained for the sample from the subject with T 2  and/or T 1  values obtained from a database, said database comprising T 2  and/or T 1  values obtained for a range of subjects, from those who are normal and healthy to those having varying degrees of inflammation, insulin resistance, lipid abnormalities, oxidative stress, brain or cognitive abnormalities and/or other disorders. 
     
     
         59 . The method according to  claim 50 , said method comprising referring an individual subject with a plasma T 2  value less than about 800 to a registered dietician, certified personal trainer, physician or other licensed health provider to improve health and well-being, and prevent the onset of diabetes, coronary artery disease, myocardial infarction, ischemic vascular disease, stroke, cognitive impairment, neurodegenerative diseases and dementia, including Alzheimer's disease, or any other diseases that arise from metabolic abnormalities such as chronic, low-grade inflammation, insulin resistance, lipid/lipoprotein abnormalities and/or oxidative stress and/or treating the subject with an appropriate treatment for inflammation, insulin resistance, lipid abnormalities, oxidative stress, brain or cognitive abnormalities and/or other disorders. 
     
     
         60 . An apparatus for health-screening a subject comprising:
 a NMR or MRI instrument or portable device tuned to measure a particular nucleus selected from  1 H,  2 H,  3 H or  17 O;   one or more computer readable storage media;   a processing system;   a data store contained on the one or more computer readable storage media comprising:   one or more reference T 2  relaxation times for water and a reference T 1  relaxation times for water, for one or more of a sample type, wherein the reference T 2  and/or reference T 1  values are associated with a health status;   program instructions for a health screening service stored on the one or more computer readable storage media that direct the processing system to:   acquire an NMR data set, relaxation decay or recovery signal, using the NMR instrument, from a sample of a particular sample type from the subject;   analyze the NMR data set or relaxation curve to extract a T 2  relaxation time for water and/or a T 1  relaxation time for water, or a surrogate of T 2  or T 1 , such as T 2 * or water peak linewidth;   identify the reference values for the particular sample type associated with the extracted T 2  and/or T 1  values or surrogate values and determine the health status associated with the reference values; and   display a health score determined from the health status.   
     
     
         61 . The apparatus according to  claim 60 , wherein the sample type is a whole blood sample, a serum sample, a plasma sample, a tissue sample or a subject, such as a human being. 
     
     
         62 . The apparatus according to  claim 60 , wherein the NMR instrument is a wearable device or is a benchtop or portable time domain NMR instrument or is a NMR spectrometer or magnetic resonance imager. 
     
     
         63 . An apparatus comprising:
 one or more computer readable storage media;   a processing system;   program instructions stored on the one or more computer readable storage media that direct the processing system to:   obtain an NMR data set or relaxation decay or recovery curve from a sample obtained from a subject, wherein the data set or relaxation curve was obtained using a NMR instrument tuned to measure a particular nucleus selected from  1 H,  2 H,  3 H or  17 O;   analyze the NMR data set or relaxation decay curve to extract a T 2  relaxation time for water and/or a T 1  relaxation time for water or a surrogate of water T 2  or T 1 , such as T 2 * or water peak linewidth;   determine a health status value of the subject, wherein the health status is determined from water T 1  and/or T 2  values, or surrogates therefor, from the sample; and   store the water T 2  and/or T 1  values, or surrogates therefor, in association with the health status in a data store contained on the one or more computer readable storage media.   
     
     
         64 . A method of treating a subject with a plasma water T 2  value less than about 800 and at risk for the development of hidden metabolic abnormalities selected from inflammation, insulin resistance, lipid abnormalities (dyslipidemia), oxidative stress, brain abnormalities or other disorders comprising obtaining a health score for a subject according to  claim 50  and treating a subject having a health score lower than about 800 for said metabolic abnormality and/or referring said subject to a physician for further evaluation. 
     
     
         65 . The method according to  claim 64 , wherein said hidden metabolic abnormality is low grade inflammation and said subject is further evaluated for treatment with one or more anti-inflammatory agents and/or treated with one or more anti-inflammatory agents. 
     
     
         66 . The method according to  claim 65 , wherein said anti-inflammatory agent is selected from ibuprofen, naproxen, aspirin, celecoxib, sulindac, oxaprozin, salsalate, diflunisal, piroxicam, indomethacin, etodolac, meloxicam, nambumetone, ketorolac tromethamine, or corticosteroids selected from as beclomethasone, beclometasone, budesonide, flunisolide, fluticasone, tramcinolone, methylprednisone, prenisolone or prednisone. 
     
     
         67 . The method according to  claim 64 , wherein said metabolic abnormality is insulin resistance and said subject is further evaluated and/or treated to improve insulin sensitivity, said treatment to improve insulin sensitivity being selected from the start or modification of an exercise and physical activity program, alteration of diet, or other modification of behavior so as to improve insulin sensitivity and reduce the likelihood of developing diabetes arising from insulin resistance. 
     
     
         68 . The method according to  claim 64 , wherein the metabolic abnormality is dyslipidemia and said subject is referred to a physician for further diagnostic evaluation and/or treated with low dose aspirin, statins and/or other lipid-lowering agents. 
     
     
         69 . The method according to  claim 68 , wherein the statin is selected from atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simcastatin. 
     
     
         70 . The method according to  claim 64 , wherein the metabolic abnormality is oxidative stress and a subject is referred to a physician and/or registered dietician to receive nutritional advice and/or is evaluated and treated with anti-oxidants such as ascorbic acid (Vitamin C), vitamin E or other nutritional supplements, and/or evaluated and treated for any accompanying inflammation or insulin resistance. 
     
     
         71 . A method of referring an individual with a plasma water T 2  value less than about 800 to a registered dietician, certified personal trainer, physician or other licensed health provider, with the goal to improve health and well-being, and prevent the onset of diabetes, coronary artery disease, myocardial infarction, ischemic vascular disease, stroke, cognitive impairment, neurodegenerative disease and dementia, including Alzheimer's disease, or any other diseases that arise from hidden metabolic abnormalities such as chronic, low-grade inflammation, insulin resistance, lipid/lipoprotein abnormalities, oxidative stress and/or brain abnormalities.