Systems and methods for microscale nuclear magnetic resonance-based disease monitoring

Abstract

The present disclosure provides a method for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having the metabolic disorder. The method comprises obtaining a plasma or blood sample from said subject, wherein said subject has been treated with one or more therapies or treatments for said metabolic disorder. The method further comprises applying a micro-scale magnetic resonance relaxometry (µMRR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample. The method further comprises periodically repeating obtaining a plasma or blood sample and applying a µNMR assay for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements. The method further comprises evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject and determine effectiveness of said one or more therapies or treatments.

Description

SYSTEMS AND METHODS FOR MICROSCALE NUCLEAR MAGNETIC RESONANCE¬BASED DISEASE MONITORINGBACKGROUND

[0001] The term “oxidative stress” as applied to biological organisms refers to an imbalance between an organism’s reactive oxygen and reactive nitrogen species and the organism’s ability to detoxify these reactive species or repair damage from them. Reactive oxygen and reactive nitrogen species, such as peroxides and free radicals, can damage different components of the cell such as proteins, lipids, and DNA. Such damage may ultimately lead to cell death.SUMMARY

[0002] Increased oxidative stress levels are associated with many different diseases, including neurodegenerative diseases, cardiovascular disease, and diabetes. However, there is currently a dearth of routinely available biomarkers for oxidative stress in clinical practice and at point-of-care locations.

[0003] The present disclosure provides systems and methods for using an oxidative stress assay to monitor disease progression. An oxidative stress assay based on microscale nuclear magnetic resonance (pNMR) may be used to monitor disease progression in patients with diabetes and / or other metabolic diseases. Additionally, the oxidative stress assay may be used to monitor disease progression during administration of one or more therapies or treatments for said metabolic diseases. This may allow for the efficacy of said therapies or treatments to be evaluated.

[0004] The present disclosure provides a method for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having the metabolic disorder, the method comprising: (a) obtaining a plasma or blood sample from the subject, wherein the subject has been treated with one or more therapies or treatments for the metabolic disorder; (b) applying a micro-scale nuclear magnetic resonance (pNMR) assay on the plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample; periodically repeating (a) and (b) for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements: and evaluating the plurality of oxidative stress measurements to monitor disease progression in the subject and determine effectiveness of the one or more therapies or treatments. In some embodiments, the blood sample is a red blood cell (RBC) sample. In some embodiments, the oxidative stress measurement is calculated as a ratio between a longitudinal proton magnetic resonance relaxation time measurement and a transverse proton magnetic resonance relaxation time measurement of the plasma or blood sample. In some embodiments, the one or more therapies or treatments for the metabolic disorder are selected from a group comprising a GLP-1 agonist, a biguanide, a meglitinide, an alpha-glucosidase inhibitor, a thiazolidinedione, a DPP -4 inhibitor, asulfonylurea, a dopamine receptor agonist, a bile acid sequestrant. an SGLT2 inhibitor, a combination medicine, incretin, an incretin derivative, an ACE inhibitor, insulin, an insulin derivative, an amylin analog, and peptide YY. In some embodiments, the GLP-1 agonist is dulaglutide, exenatide, exenatide extended- release, liraglutidc, lixisenatide, scmaglutidc injection, scmaglutidc tablets, or tirzcpatidc. In some embodiments, the biguanide is metformin. In some embodiments, the one or more therapies or treatments is a control therapy or treatment. In some embodiments, the plurality of oxidative stress measurements is used to identify side effects of the one or more therapies or treatments. In some embodiments, an initial oxidative stress level is measured in the subject and used to identify whether the subject is suffering from a metabolic disorder or disease. In some embodiments, the oxidative stress measurement is generated by analyzing one or more T1 relaxation times and one or more T2 relaxation times of the plasma or blood sample for the subject. In some embodiments, the one or more T1 relaxation times and the one or more T2 relaxation times are generated using a micro-scale nuclear magnetic resonance (pNMR) device. In some embodiments, the plurality of plasma or blood samples is collected periodically every week over a period of 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, or 20 weeks. In some embodiments, tire plurality of oxidative stress measurements is ordered longitudinally to monitor disease progression and treatment effectiveness in the subject over time. In some embodiments, the plurality of plasma or blood samples is obtained in a minimally invasive manner. In some embodiments, the plurality of plasma or blood samples is obtained at a point-of-care location. In some embodiments, the pNMR assay comprises detection of redox changes in the plurality of plasma or blood samples. In some embodiments, the redox changes comprise one or more of increased ferric ion content, increased protein oxidation, or increased lipid peroxidation. In some embodiments, the method further comprises repeating steps (a) to (d) for a plurality of subjects. In some embodiments, the plurality of oxidative stress measurements is compared between a plurality of subjects with the metabolic disorder and a plurality of subjects without the metabolic disorder. In some embodiments, results from the pNMR assay are evaluated alongside other diabetic markers or metabolic markers, the diabetic markers or metabolic markers comprising one or more of blood glucose, HbAlc, or albumin creatinine ratio, for the subject orthe plurality of subjects. In some embodiments, results from the pNMR assay allow for real-time subject risk stratification. In some embodiments, results from the pNMR assay are used for cardiometabolic risk assessment. In some embodiments, the method is used to evaluate oxidative stress in mice. In some embodiments, the method is used to evaluate oxidative stress levels in one or more of lean mice, obese mice, ob / ob mice, diabetic mice, or db / db mice treated with the one or more therapies or treatments. In some embodiments, the method is used to evaluate oxidative stress levels in ZSF-1 rats. In some embodiments, the method is used to evaluate oxidative stress levels in one or more subjects in an observational study. In some embodiments, the method is used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in mice. Insome embodiments, the method is used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes, obesity, or diabetic kidney disease. In some embodiments, the method is used to evaluate oxidative stress levels in leptin-deficient mice. In some embodiments, the method is used to evaluate oxidative stress levels in ZSF-1 rats. In some embodiments, the metabolic disorder comprises pre-diabetes, diabetes, or diabetic kidney disease.

[0005] The present disclosure provides a method of treating a subject suffering from a metabolic disorder, the method comprising administering to the subject a metabolic disorder therapy, wherein the subject has been determined to be responsive to the metabolic disorder therapy via results from a pNMR assay that measures the subject’s oxidative stress levels from one or more plasma or blood samples of the subject. In some embodiments, the method comprises: (a) collecting a first oxidative stress measurement in the subject undergoing a first treatment for a metabolic disorder or disease; at a later time from (a), collecting a second oxidative stress measurement for the subject; and comparing the first oxidative stress measurement and the second oxidative stress measurement to determine a percent change in oxidative stress for the subject. In some embodiments, the second oxidative stress measurement is collected 2-8 weeks after the first oxidative stress measurement. In some embodiments, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than a threshold, a change in treatment protocol for the subject is made. In some embodiments, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than 2%, a change in treatment protocol for the subject is made. In some embodiments, the change in treatment protocol is stopping the first treatment and starting a second treatment different from the first treatment. In some embodiments, the change in treatment protocol is increasing a dose of the first treatment. In some embodiments, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by less than 2%, the first treatment is maintained for the subject. In some embodiments, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by less than a threshold, the first treatment is maintained for the subject. In some embodiments, the subject has been determined to be responsive to the metabolic disorder therapy by the methods described herein.

[0006] The present disclosure provides a system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having tire metabolic disorder, the system comprising: a micro-scalc nuclear magnetic resonance (pNMR) device for conducting pNMR-bascd assays on a plurality of plasma or blood samples; a processor; and a memory coupled to the processor and having instructions for the processor to perform any one of the methods described herein.

[0007] The present disclosure provides a system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having tire metabolic disorder, the system comprising: a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; a processor; and a memory coupled to the processor and having instructions for the processor to: detennine oxidative stress measurements based on the iiNMR-based assays conducted on the plurality of plasma or blood samples, store the determined oxidative stress measurements, and order the determined oxidative stress measurements longitudinally, wherein one or more of disease progression or effectiveness of the one or more therapies or treatments for the metabolic disorder is determined based on the determined oxidative stress measurements that are ordered longitudinally. In some embodiments, the plurality of plasma or blood samples is collected from one or more test mice. In some embodiments, the plurality of plasma or blood samples is collected from one or more test rats. In some embodiments, the plurality of plasma or blood samples is collected at regular intervals. In some embodiments, the pNMR-based assays detect redox changes in the plurality of plasma or blood samples. In some embodiments, the redox changes comprise one or more of increased ferric ion content, increased protein oxidation, or increased lipid peroxidation. In some embodiments, the determined oxidative stress measurements are compared between a plurality of subjects with tire metabolic disorder and a plurality of subjects without the metabolic disorder. In some embodiments, results from the pNMR-based assays allow for real-time subject risk stratification. In some embodiments, results from the pNMR-based assays are used for cardiometabolic risk assessment. In some embodiments, the system is used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes. In some embodiments, the metabolic disorder comprises pre-diabetes, diabetes, or diabetic kidney disease.

[0008] Tire present disclosure provides a method for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having the disorder or disease, the method comprising: (a) obtaining a plasma or blood sample from the subject, wherein the subject has been treated with one or more therapies or treatments for the disorder or disease; (b) applying a micro-scale magnetic resonance relaxometry (pNMR) assay on the plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample; periodically repeating (a) and (b) for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements; and evaluating the plurality of oxidative stress measurements to monitor disease progression in the subject and determine effectiveness of the one or more therapies or treatments.

[0009] The present disclosure provides a method of treating a subject suffering from a disorder or disease, the method comprising administering to the subject a therapy or treatment for the disorder or disease, wherein the subject has been determined to be responsive to the therapy or treatment via results from a micro-scalenuclear magnetic resonance assay that measures the subject’s oxidative stress levels from one or more plasma or blood samples of the subject.

[0010] The present disclosure provides a system for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having tire disorder or disease, tire system comprising: a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; a processor; and a memory coupled to the processor and having instructions for the processor to: detennine oxidative stress measurements based on the uNMR-based assays conducted on the plurality of plasma or blood samples, store the detennined oxidative stress measurements, and order the determined oxidative stress measurements longitudinally, wherein one or more of disease progression or effectiveness of the one or more therapies or treatments for the disorder or disease are determined based on the determined oxidative stress measurements that are ordered longitudinally.

[0011] Tire present disclosure provides a method for monitoring disease progression in a subject with or at risk of having a metabolic disorder, tire method comprising: (a) obtaining a plasma or blood sample from the subject; (b) applying a micro-scale nuclear magnetic resonance (pNMR) assay on the plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample; periodically repeating (a) and (b) for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements; and evaluating the plurality of oxidative stress measurements to monitor disease progression in the subject. The present disclosure provides a method of evaluating the effectiveness of a treatment for diabetes, obesity, or diabetic kidney disease in a patient undergoing the treatment, the method comprising: obtaining a first measurement of an A-ratio of a patient with diabetes, obesity, or diabetic kidney disease to establish a baseline of oxidative stress, wherein an A-ratio comprises a ratio of T1 relaxation time to T2 relaxation time in a micro-scale nuclear magnetic resonance (pNMR) assay; obtaining a second measurement of the A-ratio of the patient with diabetes, obesity, or diabetic kidney disease at a later time after the first measurement; and determining a percent change between the first measurement and the second measurement. In some embodiments, the second measurement of the A-ratio is obtained at least 2 weeks after the first measurement of the A-ratio. In some embodiments, the second measurement of the A-ratio is obtained at least 3 weeks after the first measurement of the A-ratio. In some embodiments, the second measurement is obtained at least 4 weeks after the first measurement. In some embodiments, the method comprises maintaining the treatment with respect to dose and administration schedule if the percent change between the first measurement and the second measurement is less than 3% when the second measurement is taken at a time between 14 days and 21 days after the first measurement. In some embodiments, the method comprises changing the treatment by increasing a dose of tire treatment if the percent change between the first measurement and the second measurement is greater than 3% when the second measurement is taken at least 14 days after the first measurement. In some embodiments, the method comprises stopping the treatment ifthe percent change between the first measurement and the second measurement is greater than 10% when the second measurement is taken at least 2 weeks after the first measurement.INCORPORATION BY REFERENCE

[0012] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the follow ing detailed description that sets forth illustrative embodiments, in which the principles of the present disclosure are utilized, and tire accompanying drawings of which:

[0014] FIG. 1 shows a schematic of a disease progression of an individual from metabolically healthy to metabolic disease to premature death.

[0015] FIG. 2 shows a schematic of how redox imbalance in red blood cells can change the magnetic properties of blood and activate cellular oxidative stress.

[0016] FIG. 3 shows a schematic of a micro-nuclear magnetic resonance (pNMR) device and its use in measuring oxidative stress in mice or rats.

[0017] FIG. 4 shows that non-oxidized and oxidized red blood cells (RBCs) have different magnetic resonance properties.

[0018] FIG. 5 shows subclassification of ZSF-1 rats by HbA 1c level and their measured oxidative stress levels over 12-23 weeks of age.

[0019] FIG. 6 shows a graph of results for groups of ZSF-1 rats (control, obese, and GLP-1 treated obese) and their oxidative stress levels at 19 weeks of age.

[0020] FIG. 7 shows a graph of albumin-creatinine ratio vs. oxidative stress for control, obese, and GLP-1 treated obese ZSF-1 rats.

[0021] FIG. 8 shows a graph of baseline oxidative stress, HbAlc, and albumin-creatinine ratio for lean, obese, and drug-treated obese ZSF-1 rats over a period of 12 to 19 weeks of age of the rats.

[0022] FIG. 9 shows a graph of baseline oxidative stress. HbAlc, and albumin-creatinine ratio for lean, obese, and drug-treated obese ZSF-1 rats over a period of 12 to 19 weeks of age of the rats.

[0023] FIG. 10 shows a graph of baseline oxidative stress, HbAlc, and albumin-creatinine ratio for lean, obese, and drug-treated obese ZSF-1 rats over a period of 12 to 19 weeks of age of the rats.

[0024] FIG. 11 shows a graph of baseline oxidative stress, HbAlc, and albumin-creatinine ratio for lean, obese, and drug-treated obese ZSF-1 rats over a period of 12 to 19 weeks of age of the rats.

[0025] FIG. 12 shows a schematic of a method of evaluating disease progression in a subject.

[0026] FIG. 13 shows a schematic of a method of evaluating disease progression and treatment effectiveness in a subject under treatment with one or more treatments or therapies.

[0027] FIG. 14 shows a graph of oxidative stress, HbAlC, and ACR over time in groups of lean, obese, and obese GLP-1 treated mice.

[0028] FIG. 15 illustrates a quantitative relationship between age and oxidative stress in ZSF-1 lean and ZSF-1 obese rats.

[0029] FIG. 16 illustrates a quantitative relationship between age and oxidative stress in db / db diabetic and db control mice.DETAILED DESCRIPTION

[0030] Oxidative stress is a major driver in the pathogenesis of diabetes, obesity, and related cardio-renal disorders. An individual's redox balance may reflect their health. FIG. 1 shows a schematic of a progression of an individual from metabolically healthy to metabolic disease to premature death. A metabolically healthy individual may experience obesity, which can lead to diabetes, followed by kidney system damage, circulatory system damage, and chronic systemic burden, eventually leading to end organ damage and finally early death. Disrupting disease progression in diabetes and obesity may improve outcomes. Reactive oxygen species (ROS) may exist in a balance between production and scavenging. ROS production may be increased by pro-oxidant inducers. ROS scavenging may be increased by antioxidant inhibitors. When ROS production is higher than ROS scavenging, this may lead to a redox imbalance, thereby producing oxidative stress. Early detection and prevention of an oxidative stress overload can improve and potentially modify the long-term harmful outcomes associated with chronic hyperglycemia. Early detection and prevention of an oxidative stress overload can improve and potentially modify the long-term hannful outcomes associated with metabolic diseases, including chronic hyperglycemia. However, there is currently a dearth of routinely available biomarkers and tests for oxidative stress in clinical practice and at point-of-care locations.

[0031] The criteria for diabetes diagnosis in a subject may generally be HbAlc > 6.4. HbA 1c may refer to a subject’s percentage of glycosylated hemoglobin. The range 5.7-6.4 may generally be considered to be pre-diabetic. Body weight or BMI may be used for obesity diagnosis. HbAlc levels and BMI are two distinct markers that may both be looked at by a healthcare provider.

[0032] One approach that can be used to quantify the redox state of red blood cells and / or plasma is microscale nuclear magnetic resonance (pNMR). pNMR is a type of nuclear magnetic resonance (NMR) spectroscopy performed in a bench-top system. pNMR assays may allow direct measurement of proton relaxation rates and times, including both n and r2 and Ti and T2, respectively, in blood and / or plasma samples. Oxidative stress may be artificially introduced into a sample using different biochemical compounds (e.g., nitrite or peroxide). This may allow for assessment of oxidative susceptibility, tolerance, and capacity of a given sample. To detect different redox states of red blood cells (e.g., Fe2+, Fej+, Fe4+), a two-dimensional proton relaxation map, known as a T1-T2 magnetic state diagram, may be used. The assay may be performed on a small volume of plasma and / or blood at a point-of-care location in less than 10 minutes. This assay may be highly sensitive to redox changes in tire blood microenvironment, including increased ferric iron (Fel+), protein oxidation, and lipid peroxidation. FIG. 2 shows a schematic of how a redox imbalance in red blood cells may activate cellular oxidative stress in blood. Reactive oxygen species (ROS) may exist in a balance between production and scavenging. ROS production may be increased by pro-oxidant inducers. ROS scavenging may be increased by antioxidant inhibitors. When ROS production is higher than ROS scavenging, this may lead to a redox imbalance, thereby producing oxidative stress. This oxidative stress can change the magnetic properties of blood. Cellular oxidative stress in the blood may lead to chronic and / or slow onset disease, producing cellular senescence. It may also lead to acute and / or rapid onset disease, producing direct tissue damage (e.g., severe inflammation). A red blood cell in the circulatory system may undergo a changed iron oxidative state from Fe2+to Fe3+when oxidized. An oxidized red blood cell may lyse and spill its contents into the circulatory system, including oxidized Fe3+ions. An Fe2+can react with O2 in the bloodstream to produce Fe3+and OH molecules. These OH molecules can oxidize albumin or lipoproteins. The excess OH molecules may produce oxidative stress. The Fe3+ions can also enter into endothelial cells lining the bloodstream, leading to endothelial dysfunction. Oxidative stress can ultimately affect multiple different organ systems in a subject, including the urinary system and the cardiovascular system.

[0033] The bench-top pNMR system may comprise a commercial console, a detection circuit coil mounted on a micro stage, and a small permanent magnet. A microcapillary tube containing a single drop of blood may be slotted into the radio-frequency probe for pNMR analysis. Longitudinal relaxation times Tl may be measured by inversion-recovery pulse sequences observed by CPMG train pulses. Transverse relaxation times T2 may be measured by CPMG train pulses consisting of echoes. The bench-top pNMR system described herein is further described in U.S. Patent No. 10,429,467 B2, herein incorporated by reference in its entirety. The use of the bench-top pNMR system described herein for analysis of blood or plasma from a subject withdiabetes is further described in U.S. Patent No. 10,393,684 B2, herein incorporated by reference in its entirety.

[0034] FIG. 3 shows a schematic of a bench-top pNMR system and its use in measuring oxidative stress in mice or rats. FIG. 3(a) shows the steps of the assay: in vivo sampling, sample handling, data collection, and data analysis. First, a blood sample may be taken from a rat or mouse. This blood sample may be processed using sample handling techniques (e.g., centrifugation) to produce red blood cell (RBC) and plasma components. The RBC and / or plasma samples may be inserted into the bench-top pNMR system, and the T1 and T2 relaxation times measured. The data may be analyzed using software methods. Stratification of risk may be performed, and good controls vs. bad controls identified. FIG. 3(b) shows a diagram of the bench-top pNMR system. The bench-top pNMR system may comprise a permanent magnet, a radio frequency (RF) coil, and a sample holder. A sample tube with the plasma or blood sample may be inserted into the sample holder. FIG. 3(b) further shows magnetic state measurements on the bench-top pNMR system. (1), (2), (3), and (4) indicate T1 and T2 relaxation times being measured with an RF pulse. FIG. 3(c) shows that blood with increased oxidative stress has lower T1 and T2 relaxation times than blood with decreased oxidative stress.

[0035] The bench-top pNMR system may use consumables (e g., blood / plasma) with a magnetic resonance (MR) scanner. pNMR technology may leverage biophysics of large nuclear magnetic resonance (NMR) systems, enabling non-de struct! ve and label-free characterization, by aligning the nuclear spins of protons. A redox state may be assessed by plotting a magnetic state diagram of the longitudinal relaxation time and the transverse relaxation time and interpreting the state of the sample based on the location of the sample in the diagram. Assessing the redox state can include calculating a ratio of longitudinal relaxation time to transverse relaxation time of the sample and comparing the ratio with a predetermined ratio of a reference sample. Plasma may provide some advantages over RBCs in terms of diagnostic use, as they may have increased diagnostic accuracy compared to RBCs. FIG. 4 shows that non-oxidized and oxidized red blood cells have different magnetic resonance properties. Oxidized RBCs may contain Fe3+pockets. In some cases, magnetic nanoparticles can be delivered in an in-vitro stress test to increase both T1 and T2 relaxation contrasts based on specific targets of interest. For example, a cysteine pocket in human serin albumin (HSA) may be targeted by these magnetic nanoparticles. In some cases, specific immune cells may be deployed in an in-vitro stress test delivered to red blood cells to bind to a specific target. In some cases, this specific target may be mRNA.

[0036] Hereinafter, the present disclosure will be described in more detail to help the understanding of the present disclosure.

[0037] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method,article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0038] The transitional phrase ‘'consisting of’ excludes any element, step, or ingredient not specified in the claim, closing the claim to tire inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consists of’ appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

[0039] The transitional phrase “consisting essentially of’ limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claimed embodiment. A “consisting essentially of’ claim occupies a middle ground between closed claims that are written in a “consisting of’ format and fully open claims that are drafted in a “comprising” format. Optional additives as defined herein, at a level that is appropriate for such additives, and minor impurities are not excluded from a composition by the term “consisting essentially of’.

[0040] Tire use of “a” or “an” to describe the various elements and components herein is merely for convenience and to give a general sense of the disclosure. Uris description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise. Further, unless expressly stated to the contrary, “or” and '‘and / or” refers to an inclusive and not to an exclusive. For example, a condition A or B, or A and / or B, is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

[0041] When the term “about” is used, it is used to mean a certain effect or result can be obtained within a certain tolerance, and the skilled person knows how to obtain the tolerance. When the term “about” is used in describing a value or an end-point of a range, the disclosure should be understood to include the specific value or end-point referred to. In one aspect, the term “about” means plus or minus 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% of the numerical value of the number with which it is being used.

[0042] The present disclosure provides a method for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having tire metabolic disorder (FIG. 13). A plasma or blood sample from the subject may be obtained. The blood sample may be an RBC sample. A subject may be an animal, such as a mammal. A subject may be a human or non-human mammal. A subject may be a plant. A subject may be afflicted with a disease or suspected of being afflicted with or having a disease. The subject may not be suspected of being afflicted with or having the disease. The subject may be symptomatic. Alternatively, the subject may be asymptomatic. In some cases, the subject may be treated to alleviate tire symptoms of the disease or cure the subject of the disease. A subject may be a patient undergoingtreatment by a healthcare provider, such as a doctor. The subject may have been treated with one or more therapies or treatments for the metabolic disorder (1301). The one or more therapies or treatments for the metabolic disorder may be selected from a group comprising a GLP-1 agonist, a biguanide, a meglitinide, an alpha-glucosidasc inhibitor, athiazolidincdionc, a DPP -4 inhibitor, a sulfonylurea, a dopamine receptor agonist, a bile acid sequestrant, an SGLT2 inhibitor, a combination therapy, incretin, an incretin derivative, an ACE inhibitor, insulin, an insulin derivative, an amylin analog, and peptide YY. In some cases, the meglitinide may be repaglinide or nateglinide. In some cases, the alpha-glucosidase inhibitor may be miglitol or acarbose. In some cases, the thiazolidinedione may be pioglitazone or rosiglitazone. In some cases, the DPP-4 inhibitor may be sitagliptin, saxagliptin, alogliptin, or linagliptin. In some cases, the sulfonylurea may be glimepiride, glyburidc, chlorpropamide, glipizide, tolbutamide, or tolazamide. In some cases, the GLP-1 agonist may be dulaglutide, exenatide, exenatide extended-release, liraglutide. lixisenatide, semaglutide injection, semaglutide tablets, or tirzepatide. In some cases, the biguanide may be metformin. In some cases, the dopamine receptor agonist may be bromocriptine. In some cases, the bile acid sequestrant may be colesevelam. In some cases, the SGLT2 inhibitor may be dapagliflozin, canagliflozin, empagliflozin, or ertugliflozin. In some cases, the combination therapy may be pioglitazone / metfonnin, rosiglitazonemetfonnin, rosiglitazone / glimepiride, pioglitazone / glimepiride. glyburide / metformin, empagliflozin / linagliptin, canagliflozin / metformin, sitagliptin / metformin, linagliptin / metformin, alogliptin / metformin, saxagliptin / metformin, glipizide / metformin. alogliptin / pioglitazone. repaglinide / metformin, or dapagliflozin / metformin. In some cases, the amylin analog may be pramlintide acetate. In some cases, said one or more therapies or treatments may be a control therapy or treatment. In some cases, a positive control may be used in evaluating the effectiveness of the one or more therapies or treatments. The positive control may comprise a therapeutic agent or other treatment that has been well- established as therapeutically effective to treat the metabolic disorder, including, but not limited to, any one or more of the aforementioned.

[0043] As used herein, “evaluate;’ “evaluating” may refer calculating, determining or judging the quality or amount or value of something. It may also mean determining the significance or condition of a study.

[0044] As used herein, “treating,” “treatment” may refer preventing (i.e. keeping from happening), reducing or alleviating at least one adverse effect or symptom of a disease, disorder or condition. It may refer to both therapeutic treatment and prophylactic or preventative measures; wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. In some embodiments, those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.

[0045] ‘'Metabolic disorder,” or “metabolic symdrom” may refer to disorders, diseases and conditions caused or characterized by abnormal weight gain, energy use or consumption, altered responses to ingested or endogenous nutrients, energy sources, hormones or other signaling molecules within the body or altered metabolism of carbohydrates, lipids, proteins, nucleic acids or a combination thereof. A metabolic disorder may be associated with either a deficiency or an excess in a metabolic pathway resulting in an imbalance in metabolism of carbohydrates, lipids, proteins and / or nucleic acids. Examples of metabolic disorders may include, but are not limited to, metabolic syndrome, insulin-deficiency or insulin-resistance related disorders, Diabetes Mellitus (such as, for example, Type 2 Diabetes), glucose intolerance, abnormal lipid metabolism, atherosclerosis, hypertension, cardiac pathology, stroke, non-alcoholic fatty liver disease, hyperglycemia, hepatic steatosis, dyslipidemia, dysfunction of the immune system associated with overweight and obesity, cardiovascular diseases, high cholesterol, elevated triglycerides, asthma, sleep apnoea, osteoarthritis, neurodegeneration, gallbladder disease, syndrome X, inflammatory and immune disorders, atherogenic dyslipidemia and cancer. The metabolic disorder may be selected from the group of obesity, Type 2 Diabetes, Metabolic Syndrome, lipodystrophy, impaired glucose tolerance, elevated plasma insulin concentrations, insulin resistance, dyslipidemia, hyperglycemia, hyperlipidemia, hypertension, cardiovascular disease or respiratory problems.

[0046] “Metabolic disorder” also may mean a condition characterized by an alteration or disturbance in one or more metabolic processes in the body. Metabolic disorders may include, but are not limited to, hyperglycemia, prediabetes, diabetes, type 1 diabetes, type 2 diabetes, obesity, diabetic dyslipidemia, metabolic syndrome, and hyperinsulinemia. '‘Diabetes” or “diabetes mellitus” may mean a disease in which the body does not produce or properly use insulin, resulting in abnormally high blood glucose levels.

[0047] Metabolic syndrome may be a group of conditions that together increase risk of cardiovascular disease, Type 2 diabetes, and stroke. It may lead to other health problems as well, like conditions related to plaque buildup in artery walls (atherosclerosis) and organ damage. It may includes syndrome X. insulin resistance syndrome, and dysmetabolic syndrome. A person may meet the criteria for metabolic syndrome if they have at least three of the following: excess abdominal weight (a waist circumference of more than 40 inches in males and 35 inches in females), hypertriglyceridemia (150 mg / dL or greater), low levels of HDL cholesterol (less than 40 mg / dL in males or less than 50 mg / dL in females), elevated blood sugar levels (fasting blood sugar level of 100 mg / dL or greater. If it’s 100 to 125 mg / dL, you have prediabetes. If it’s over 125 mg / dL, you likely have Type 2 diabetes), and high blood pressure (systolic 130 mmHg or higher (the top number) and / or diastolic 85 mmHg or higher (the bottom number)).

[0048] Several factors may contribute to the development of metabolic syndrome, but insulin resistance may be the main driver behind the syndrome. The insulin resistance and hyperinsulinemia may contribute toobcsity. cardiovascular disease, fatty liver disease, polycystic ovary syndrome. Metabolic syndrome may lead to a wide range of complications, including heart disease, aortic stenosis, atrial fibrillation, thromboembolic disease, stroke, organ damage, especially damage to your pancreas, liver, gallbladder and kidneys, certain cancers, like colon cancer, breast cancer and prostate cancer, type 2 diabetes, long-term inflammation and problems with your immune system, erectile dysfunction, pregnancy complications, such as preeclampsia, eclampsia and gestational diabetes, issues with thinking and memory.

[0049] Treatment of metabolic syndrome may involve medication and / or lifestyle changes. Lifestyle changes may include lose excess weight, regular exercise, eating heart-healthy food, getting quality sleep, avoiding or quitting smoking, and managing stress. Medication treatment may include cholesterol medications, such as Statins (HMG CoA reductase inhibitors), blood pressure medications, such as thiazide, ACE inhibitors and calcium channel blockers, oral diabetes medications, such as metformin, a biguanide, bariatric surgery, or psychotherapy. In some cases, metabolic disease is a chronic disease.

[0050] As used herein, the tenns “obesity” may be defined in general terms as an excess of body fat relative to lean body mass. A body mass index (BMI) of 30 or higher may be commonly used for health (and medical) recommendations and clinical decisions. A more precise assessment of a person's obesity may also involve the use of anthropomorphic measurements (e g., waist circumference, waist-height ratio, waist-hip ratio, etc.), biological (hyper-triglyceridemic waist, metabolites, genomic markers, etc.), and imaging (e.g., CT, MRI, DXA, etc.). There may be a number of individual metabolites that are known to be associated with BMI and obesity. These include branched chain amino acids (leucine, isoleucine, valine), aromatic amino acids (tyrosine, tryptophan), uric acid, phospholipids, glucose, mannose, asparagine, glycerol, and glycerophosphocholines. However, these metabolites are not currently considered singly or in aggregate to calculate a person's metabolic BMI (mBMI). Obesity may be often associated with psychological and medical morbidities, the latter of which includes increased joint problems, vascular diseases such as coronary artery disease, hypertension, stroke, and peripheral vascular disease. Obesity also causes metabolic abnormalities such as insulin resistance and Type II diabetes (non-insulin-dependent diabetes mellitus (NIDDM)), hyperlipidemia, and endothelial dysfunction. These abnormalities predispose the vasculature to injury, cellular proliferation and lipid oxidation, with resulting atherosclerosis leading to heart attack, stroke, and peripheral vascular diseases. Many co-morbidities may be associated with obesity, such as type 2 diabetes, hypertension, dyslipidemia, coronary heart disease. Insulin resistance may be a condition of tolerance to insulin, making the hormone less effective, causing decreased glucose uptake in muscle tissue that result in impaired glucose oxidation and glycogen synthesis, and a deficient suppression of hepatic glucose production in the liver. In obese, increased visceral fat mass with elevation of plasma free fatty acid (FFA) caused by the intensified lipolytic activity, worsen insulin resistance through the impairment of insulin action, a mechanism known as lipotoxicity. High concentrations of FFA in skeletal muscle cells may lead to reduction in insulin-stimulated intracellular transport of glucose through the Glut4 transporter, in the hepatocytes lead to enhanced rate of gluconeogenesis and glucose release from the liver and augmented insulin secretion from p cells in response to a transient increase of FFA or an inhibition effect in response to chronic elevated levels. As a result of insulin resistance and lipotoxicity, more insulin may be needed to induce glucose uptake from fat and muscle cells, and glycogen synthesis in the liver. The overproduction of insulin by pancreatic cells may be the physiologic reaction to insulin resistance and may lead to decline of P cell function and, eventually to prediabetes and type 2 diabetes. Genetic predisposition, age and lifestyle (ovcrwcight / obcsity and inactivity) may be risk factors for insulin resistance. Moreover, insulin resistance associated with type 2 diabetes may be responsible for inadequate glycemic control, leading to failure of oral hypoglycemic agents (OHA) and, eventually, the need to initiate insulin therapy

[0051] Obesity treatment may be challenging. Lifestyle interventions are effective in the setting of clinical trials with intensive counseling, but not as effective in real life due to difficulty in adherence and maintenance. Obesity pharmacotherapy may be limited, associated with side effects and results in loss of both fat body mass (FBM) and lean body mass (LBM). Weight loss studies have consistently shown loss of lean tissue on the order of 'Ath of loss of body composition.

[0052] In some cases, the method further comprises obtaining a sample from a subject. In some cases, the subject may be a mammalian subject. Tire mammalian subject may be an equine, feline, canine, bovine or porcine animal. Tire subject may be a human. In some cases, subject may suffer from metabolic disease. In some cases, subject may suffer from chronic metabolic disease. In some cases, subject may suffer from obese. In some case, subject may suffer from metabolic disease and administered one more more treatment or metabolic disease. In some case, subject may suffer from obese and administered one more more treatment of obese. In some case, subject may administered GLP-1 treatment of obese.

[0053] In some cases, the sample comprises at least one selected from the group consisting of whole blood, serum, plasma, urine, saliva, sweat, fecal matter, and tears of a subject. In some embodiments of the method disclosed herein, the sample comprises a blood sample. In some embodiments of the method disclosed herein, the blood sample is plasma. In some embodiments of the method disclosed herein, the blood sample is red blood cells. In some embodiments, the sample may be body fluid, tissue, or cell sample. In some embodiments, the body fluid may be blood, sweat, or urine. In some embodiments, the blood sample may be plasma, serum, or red blood cells.

[0054] A micro-scale nuclear magnetic resonance (pNMR) assay may be applied to said plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample (1302). In some cases, the pNMR assay comprises detection of redox changes in said plurality of plasma or blood samples. In some cases, tire redox changes comprise one or more of increased ferric ion content, increased protein oxidation, orincreased lipid peroxidation. The oxidative stress measurement may be calculated as a ratio between a longitudinal proton magnetic resonance relaxation time measurement and a transverse proton magnetic resonance relaxation time measurement of tire plasma or blood sample. A plurality of oxidative stress measurements may be obtained by periodically repeating the obtainment of a plasma or blood sample and the application of the LLNMR assay to the plasma or blood sample (1303). Tire plurality of oxidative stress measurements may be evaluated to monitor the disease progression in the subject and determine effectiveness of the one or more therapies or treatments (1304). The plurality of oxidative stress measurements may be used to identify side effects of the one or more therapies or treatments. In some cases, an initial oxidative stress level may be measured in the subject and used to identify whether the subject is suffering from a metabolic disorder or disease. In some cases, an oxidative stress measurement may be generated by analyzing one or more T1 relaxation times and one or more T2 relaxation times of a plasma or blood sample for a subject. In some cases, the one or more T1 relaxation times and one or more T2 relaxation times may be collected using a pNMR device.

[0055] In some cases, tire plurality of plasma or blood samples may be collected periodically every week over a period of 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, or 20 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every two weeks over a period of 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, 18 weeks, or 20 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every three weeks over a period of 6 weeks. 9 weeks, 12 weeks. 15 weeks, 18 weeks, or 21 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every week. In some cases, the plurality of plasma or blood samples may be collected periodically every 2 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every 3 weeks. In some cases, tire plurality of plasma or blood samples may be collected periodically every 4 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every 5 weeks. In some cases, the plurality of plasma or blood samples may be collected periodically every 6 weeks.

[0056] In some cases, tire plurality of samples may be collected monthly. In some cases, the plurality of samples may be collected monthly over a period of 1 month, 2 months, 3 months. 4 months. 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 15 months, 18 months, 21 months, 24 months, 27 months, 30 months, 33 months, or 36 months. In some cases, the plurality of plasma or blood samples may be collected periodically every two months over a period of 4 months. 6 months, 8 months, 10 months, 12 months, 14 months, 16 months, 18 months, 20 months, 22 months, or 24 months. In some cases, the plurality of plasma or blood samples may be collected periodically every three months over a period of 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, 24 months, 27 months, 30 months, 33 months, or 35 months. In some cases, the plurality of plasma or blood samples may be collectedperiodically every month. In some cases, the plurality of plasma or blood samples may be collected periodically every 2 months. In some cases, the plurality of plasma or blood samples may be collected periodically every 3 months. In some cases, the plurality of plasma or blood samples may be collected periodically every 4 months. In some cases, the plurality of plasma or blood samples may be collected periodically every 5 months. In some cases, the plurality of plasma or blood samples may be collected periodically every 6 months.

[0057] In some cases, the plurality of samples may be collected daily. In some cases, the plurality of samples may be collected daily over a period of 5 days, 6 days, 7 days. 8 days. 9 days. 10 days, 11 days. 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 10 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, or 31 days. In some cases, the plurality of samples may be collected hourly. In some cases, the plurality of samples may be collected hourly over a period of 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours. 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours.

[0058] In some cases, the plurality samples may be collected periodically between about 0.5 hour to about 20 weeks, 1 hour to about 20 weeks, 2 hours to about 20 weeks, 3 hours to about 20 weeks. 4 hours to about 20 weeks, 6 hours to about 20 weeks, 9 hours to about 20 weeks, 12 hours to about 20 weeks, 15 hours to about 20 weeks, 18 hours to about 20 weeks, 21 hours to about 20 weeks, 24 hours to about 20 weeks, 0.5 hour to about 21 weeks, 1 hour to about 18 weeks, 2 hours to about 18 weeks, 3 hours to about 18 weeks, 4 hours to about 18 weeks, 6 hours to about 18 weeks, 9 hours to about 18 weeks, 12 hours to about 18 weeks, 15 hours to about 18 weeks, 18 hours to about 18 weeks, 21 hours to about 18 weeks. 24 hours to about 18 weeks, 0.5 hour to about 15 weeks. 1 hour to about 15 weeks. 2 hours to about 15 weeks. 3 hours to about 15 weeks. 4 hours to about 15 weeks, 6 hours to about 15 weeks, 9 hours to about 15 weeks, 12 hours to about 15 weeks, 15 hours to about 15 weeks, 18 hours to about 15 weeks, 21 hours to about 15 weeks, 24 hours to about 15 weeks, 0.5 hour to about 12 weeks, 1 hour to about 12 weeks, 2 hours to about 12 weeks, 3 hours to about 12 weeks, 4 hours to about 12 weeks, 6 hours to about 12 weeks, 9 hours to about 12 weeks, 12 hours to about 12 weeks, 15 hours to about 12 weeks, 18 hours to about 12 weeks. 21 hours to about 12 weeks, 24 hours to about 12 weeks. 0.5 hour to about 9 weeks, 1 hour to about 9 weeks, 2 hours to about 9 weeks, 3 hours to about 9 weeks, 4 hours to about 9 weeks, 6 hours to about 9 weeks, 9 hours to about 9 weeks, 12 hours to about 9 weeks, 15 hours to about 9 weeks, 18 hours to about 9 weeks, 21 hours to about 9 weeks, 24 hours to about 9 weeks, 0.5 hour to about 6 weeks, 1 hour to about 6 weeks, 2 hours to about 6 weeks, 3 hours to about 6 weeks, 4 hours to about 6 weeks, 6 hours to about 6 weeks, 9 hours to about 6 weeks, 12 hours to about 6 weeks, 15 hours to about 6 weeks. 18 hours to about 6 weeks, 21 hours to about 6 weeks, 24 hours to about 6 weeks, 0.5 hour to about 3 weeks, 1 hour to about 3 weeks, 2 hours to about 3 weeks, 3 hours to about 3 weeks, 4 hours to about 3 weeks, 6 hours to about 3 weeks, 9 hours to about 3 weeks, 12 hours to about 3weeks, 15 hours to about 3 weeks. 18 hours to about 3 weeks. 21 hours to about 3 weeks, or 24 hours to about 3 weeks.

[0059] In some cases, the plurality of oxidative stress measurements may be ordered longitudinally to monitor disease progression and treatment effectiveness in said subject overtime. In some cases, the plurality' of plasma or blood samples may be obtained in a minimally invasive manner. In some cases, the plurality of plasma or blood samples may be obtained at a point-of-care location. In some cases, the plurality of plasma or blood samples may be obtained at a clinical office location. In some cases, the method further comprises repeating the steps of obtaining a plurality of plasma or blood samples and applying the pNMR assay to each plasma or blood sample for a plurality of subjects. In some cases, the plurality of oxidative stress measurements may be compared between a plurality' of subjects with the metabolic disorder and a plurality of subjects without tire metabolic disorder. In some cases, results from the pNMR assay may be evaluated alongside other diabetic markers or metabolic markers, tire diabetic markers or metabolic markers comprising one or more of blood glucose, HbAlc. or albumin creatinine ratio, for the subject or the plurality of subjects.

[0060] In some cases, an initial oxidative stress level may be measured in a subject and used to identify whether the subject is suffering from a metabolic disorder or disease. In some cases, results from the pNMR assay may allow for real-time subject risk stratification. In some cases, results from the pNMR assay may? be used for cardiometabolic risk assessment. In some cases, the method may be used to evaluate oxidative stress in mice. In some cases, the method may be used to evaluate oxidative stress levels in one or more of lean mice, obese mice, ob / ob mice, diabetic mice, or db / db mice treated with the one or more therapies or treatments described herein. Tire db / db mouse model may be a mouse model frequently used in preclinical studies to model phase 1 to 3 of type-2 diabetes. In the db / db mouse model, a mutation in the gene encoding the leptin receptor confers susceptibility? to obesity, insulin resistance, and type-2 diabetes. Mice with these mutations may be frequently demonstrate chronic hyperglycemia and pancreatic beta cell atrophy, and may become hypoinsulinemic. + / db control mice may be carriers of the mutated gene of the leptin receptor but do not become diabetic at any point in their lifespans, db / db mice may have both copies of the mutated gene and therefore become diabetic. In some cases, the method may be used to evaluate oxidative stress levels in ZSF-1 rats. The ZSF-1 rat model may be a preclinical model of type-2 diabetes nephropathy. The ZSF-1 rat model may be the result of crossing the lean female Zucker diabetic fatty' rat (ZDF; C / fa) and the lean male spontaneously hypertensive heart failure rat (SHHF; C / facp). Both lean and obese rats may inherit the gene for hypertension and may have elevated blood pressure. Obese rats may also develop dyslipidemia, hyperglycemia, renal sclerosis, and fibrosis. ZSF-1 obese rats may develop type 2 diabetes and kidney disease by 12 weeks of age. ZSF-1 obese rats may also develop renal fibrosis by 20 weeks that progresses overtime. Both lean and obese ZSF-1 obese rats may inherit the gene for hypertension and have similarly elevated blood pressure, but only obese ZSF-1 rats (fa / facp) develop dyslipidemia, hyperglycemia, renal sclerosis, andfibrosis. In some cases, the method may be used to evaluate oxidative stress levels in one or more subjects in an observational study. In some cases, the method may be used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in mice. In some cases, the method may be used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes. In some cases, the method may be used to evaluate oxidative stress levels in leptin-deficient mice. In some cases, the method may be used to evaluate oxidative stress levels in ZSF-1 rats. In some cases, the metabolic disorder comprises pre-diabetes, diabetes, obesity, or diabetic kidney disease.

[0061] The present disclosure provides a method of treating a subject suffering from a metabolic disorder, the method comprising administering to the subject a metabolic disorder therapy, wherein the subject has been determined to be responsive to the metabolic disorder therapy via results from a pNMR assay that measures the subject’s oxidative stress levels from one or more plasma or blood samples of the subject. In some cases, the method comprises collecting a first oxidative stress measurement in a subject undergoing a first treatment for a metabolic disorder or disease; at a later time, collecting a second oxidative stress measurement for the subject; and comparing tire first oxidative stress measurement and the second oxidative stress measurement to determine a percent change in oxidative stress for the subject. In some cases, the second oxidative stress measurement may be collected 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks after the first oxidative stress measurement. In some cases, the second oxidative stress measurement may be collected 1 day, 2 days, 3 days, 4 days, 5 days, 6 days. 7 days, 8 days, 9 days, 10 days, 11 days. 12 days, 13 days, or 14 days. In some cases, the second oxidative stress measurement may be collected 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks. In some cases, the second oxidative stress measurement may be collected 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months. In some cases, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than a threshold, a change in treatment protocol for the subject is made. In some cases, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than 2%, a change in treatment protocol for the subject may be made. In some cases, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress forthat subject’s species by greater than at least 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9. 3, 3.1, 3.2, 3.3, 3.4. 3.5, 3.6, 3.7, 3.8, 3.9. 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 6, 7, 8, 9, 10, 11, 12. 13. 14. 15, 16, 17, 18, 19, or 20%, a change in treatment protocol for the subject may be made.

[0062] In some cases, tire change in treatment protocol may be stopping the first treatment and starting a second treatment different from the first treatment. In some cases, the change in treatment protocol may be increasing a dose of the first treatment. In some cases, the change in treatment protocol may be increasing atleast 0.1, 0.2, 0.3, 0.4. 0.5. 0.6, 0.7, 0.8, 0.9. 1. 1.1, 1.2, 1.3, 1.4. 1.5. 1.6, 1.7, 1.8, 1.9. 2, 2.1, 2.2, 2.3. 2.4. 2.5,2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% a dose of the first treatment. In some cases, the change in treatment protocol may be increasing at most 99, 98, 97, 96, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20. 15, or 10 % a dose of the first treatment. In some cases, the change in treatment protocol may be increasing from about 5 to about 99. from about 5 to about 95. from about 5 to about 90, from about 5 to about 85, from about 5 to about 80, from about 5 to about 75, from about 5 to about 70, from about 5 to about 65, from about 5 to about 60, from about 5 to about 55, from about 5 to about 50, from about 5 to about 45, from about 5 to about 40, from about 5 to about 35, from about 5 to about 30, from about 5 to about 25, from about 5 to about 20, from about 5 to about 15, from about 5 to about 10, from about 10 to about 99, from about 10 to about 95, from about 10 to about 90, from about 10 to about 85, from about 10 to about 80, from about 10 to about 75, from about 10 to about 70, from about 10 to about 65, from about 10 to about 60, from about 10 to about 55, from about 10 to about 50, from about 10 to about 45, from about 10 to about 40, from about 10 to about 35, from about 10 to about 30, from about 10 to about 25, from about 10 to about 20, from about 15 to about 99, from about 15 to about 95, from about 15 to about 90, from about 15 to about 85, from about 15 to about 80, from about 15 to about 75, from about 15 to about 70, from about 15 to about 65, from about 15 to about 60, from about 15 to about 55, from about 15 to about 50, from about 15 to about 45, from about 15 to about 40, from about 15 to about 35, from about 15 to about 30. from about 15 to about 25, from about 15 to about 20, from about 20 to about 99, from about 20 to about 95, from about 20 to about 90, from about 20 to about 85, from about 20 to about 80, from about 20 to about 75, from about 20 to about 70, from about 20 to about 65, from about 20 to about 60, from about 20 to about 55, from about 20 to about 50, from about 20 to about 45, from about 20 to about 40, from about 20 to about 35, from about 20 to about 30, from about 30 to about 99, from about 30 to about 95, from about 30 to about 90, from about 30 to about 85, from about 30 to about 80, from about 30 to about 75, from about 30 to about 70. from about 30 to about 65, from about 30 to about 60, from about 30 to about 55, from about 30 to about 50, from about 30 to about 45, or from about 30 to about 40 % a dose of the first treatment. In some cases, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by less than 2%, tire first treatment may be maintained for the subject. In some cases, if the percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by less than at most 0.1, 0.2, 0.3. 0.4, 0.5, 0.6, 0.7, 0.8. 0.9, 1, 1.1, 1.2. 1.3. 1.4, 1.5,1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20%, the first treatment may be maintained for the subject.

[0063] In some cases, if the percent change in oxidative stress for the subject deviates from a standard age- related progression of oxidative stress for that subject’s species by less than a threshold, the first treatment may be maintained for the subject. In some cases, the subject has been determined to be responsive to the metabolic disorder therapy by the methods described herein.

[0064] Tire present disclosure provides a sy stem for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having the metabolic disorder. Uris system may comprise a pNMR device for conducting pNMR-based assays on a plurality of plasma or blood samples, a processor, and a memory coupled to the processor and having instructions for the processor to perform any one of the methods described herein.

[0065] The present disclosure provides a system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having tire metabolic disorder. The system may comprise a micro-scale nuclear magnetic resonance (pN MR) device for conducting an pNMR-based assay on a plurality of plasma or blood samples. Tire system may further comprise a processor. The system may further comprise a memory coupled to the processor and having instructions for the processor to: (i) determine oxidative stress measurements based on the pNMR-based assays conducted on the plurality of plasma or blood samples, (ii) store the determined oxidative stress measurements, and (iii) order the determined oxidative stress measurements longitudinally. One or more of disease progression or effectiveness of tire one or more therapies or treatments for the metabolic disorder may be determined based on the determined oxidative stress measurements that are ordered longitudinally. In some cases, the plurality of plasma or blood samples is collected from one or more test mice. In some cases, the plurality of plasma or blood samples is collected from two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more test mice. In some cases, the plurality of plasma or blood samples is collected from one or more test rats. In some cases, the plurality of plasma or blood samples is collected from two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more test rats. In some cases, the plurality of plasma or blood samples is collected at regular intervals. In some cases, the plurality of plasma or blood samples is collected at irregular intervals. In some cases, the pNMR assay may detect redox changes in the plurality of plasma or blood samples. In some cases, the redox changes comprise one or more of increased ferric ion content, increased protein oxidation, or increased lipid peroxidation. In some cases, the plurality of oxidative stress measurements may be compared between a plurality of subjects with the metabolic disorder and a plurality of subjects without the metabolic disorder. In some cases, results from the pNMR assay may allow for real-time subject risk stratification. In some cases, results from said pNMR assay may be used for cardiometabolic risk assessment. In some cases, the system may be used to evaluate one or more effects of the one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes. In some cases, themetabolic disorder comprises pre-diabetes, diabetes, or diabetic kidney disease. In some cases, the metabolic disorder comprises pre-diabete. In some cases, the metabolic disorder comprises diabetes. In some cases, the metabolic disorder comprises diabetic kidney disease.

[0066] The present disclosure provides a method for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having tire disorder or disease. The method may comprise obtaining a plasma or blood sample from the subject, wherein the subject has been treated with one or more therapies or treatments for the disorder or disease. In some cases, the subject has been treated with two or more, three or more, four or more, or five or more therapies or treatment for the disorder of disease. In some cases, the subject has not been treated with therapies or treatment for the disorder or disease. The method may further comprise applying a micro-scale nuclear magnetic resonance (pNMR) assay on the plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample. The method may further comprise periodically repeating the obtainment of a plasma or blood sample and tire application of the pNMR assay for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements. The method may further comprise periodically repeating the obtainment of sample and the application of the pNMR assay for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements. The method may further comprise evaluating the plurality of oxidative stress measurements to monitor the disease progression in the subject and determine effectiveness of the one or more therapies or treatments.

[0067] The present disclosure provides a method of treating a subject suffering from a disorder or disease, the method comprising administering to the subject a therapy or treatment for the disorder or disease, wherein the subject has been determined to be responsive to the therapy or treatment via results from a micro-scale magnetic resonance relaxometry assay that measures the subject’s oxidative stress levels from one or more plasma or blood samples of the subject. In some cases, a micro-scale magnetic resonance relaxometry assay may measure the subject’s oxidative stress levels from one or more samples of the subject.

[0068] Tire present disclosure provides a system for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having the disorder or disease. Tire system may comprise a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR based assays on a plurality of plasma or blood samples. The system may further comprise a processor. The system may further comprise a memory coupled to the processor and having instructions for the processor to: (i) determine oxidative stress measurements based on tire pNMR based assays conducted on the plurality of plasma or blood samples, (ii) store the determined oxidative stress measurements, and (iii) order the determined oxidative stress measurements longitudinally, wherein one or more of disease progression oreffectiveness of the one or more therapies or treatments for the disorder or disease are determined based on the determined oxidative stress measurements that are ordered longitudinally.

[0069] The present disclosure provides a method for monitoring disease progression in a subject with or at risk of having a metabolic disorder (FIG. 12). The method may comprise obtaining a plasma or blood sample from the subject (1201). The method may comprise obtaining a sample from the subject. The method may further comprise applying a micro-scale nuclear magnetic resonance (LINMR) assay on the plasma or blood sample to generate an oxidative stress measurement of the plasma or blood sample (1202). The method may- further comprise applying a micro-scale nuclear magnetic resonance (pNMR) assay on sample to generate an oxidative stress measurement of the sample. The method may further comprise periodically repeating the obtainment of a plasma or blood sample and the application of the pNMR assay for a plurality of plasma or blood samples from the subject to generate a plurality of oxidative stress measurements (1203). The method may further comprise periodically repeating the obtainment of a sample and the application of the pNMR assay for a plurality of samples from the subject to generate a plurality of oxidative stress measurements. The method may further comprise evaluating the plurality of oxidative stress measurements to monitor disease progression in the subject (1204).

[0070] The present disclosure provides a method for evaluating the effectiveness of a treatment for diabetes, obesity, or diabetic kidney disease in a patient undergoing the treatment. The method may comprise obtaining a first measurement of an A-ratio of a patient with diabetes, obesity, or diabetic kidney disease to establish a baseline of oxidative stress. The method may further comprise obtaining a second measurement of the A-ratio of the patient with diabetes, obesity, or diabetic kidney disease at a later time after the first measurement. The method may further comprise determining a percent change between the first measurement and the second measurement.

[0071] In some embodiments of the method disclosed herein, a “Ratio A,” “a ratio,” “ratio-a,” “a-ratio” may be used interchangeably. In some embodiments of the method disclosed herein, Ratio A is a ratio of Ti and T2(TJ / T2).

[0072] In some cases, the second measurement is obtained at least 2 weeks after the first measurement. In some cases, the second measurement is obtained at least 3 weeks after the first measurement. In some cases, the second measurement is obtained at least 4 weeks after the first measurement. In some cases, the second measurement may be obtained at least 1, 2, 3, 4. 5, 6, 7, 8. 9, 10, 11. 12. 13, or 14 days after the first measurement. In some cases, the second measurement may be obtained at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 weeks after the first measurement. In some cases, the second measurement may be obtained from about 1 day to about 30 weeks, from about 2 days to about 30 weeks, from about 3 days to about 30 weeks, from about 4 days to about 30 weeks, from about 5 days to about 30weeks, from about 6 days to about 30 weeks, from about 1 week to about 30 weeks, from about 2 weeks to about 30 weeks, from about 3 weeks to about 30 weeks, from about 4 weeks to about 30 weeks, from about 5 weeks to about 30 weeks, from about 6 weeks to about 30 weeks, from about 7 weeks to about 30 weeks, from about 8 weeks to about 30 weeks, from about 9 weeks to about 30 weeks, from about 10 weeks to about 30 weeks, from about 1 day to about 20 weeks, from about 2 days to about 20 weeks, from about 3 days to about 20 weeks, from about 4 days to about 20 weeks, from about 5 days to about 20 weeks, from about 6 days to about 20 weeks, from about 1 week to about 20 weeks, from about 2 weeks to about 20 weeks, from about 3 weeks to about 20 weeks, from about 4 weeks to about 20 weeks, from about 5 weeks to about 20 weeks, from about 6 weeks to about 20 weeks, from about 7 weeks to about 20 weeks, from about 8 weeks to about 20 weeks, from about 9 weeks to about 20 weeks, from about 10 weeks to about 20 weeks, from about 1 day to about 15 weeks, from about 2 days to about 15 weeks, from about 3 days to about 15 weeks, from about 4 days to about 15 weeks, from about 5 days to about 15 weeks, from about 6 days to about 15 weeks, from about 1 week to about 15 weeks, from about 2 weeks to about 15 weeks, from about 3 weeks to about 15 weeks, from about 4 weeks to about 15 weeks, from about 5 weeks to about 15 weeks, from about 6 weeks to about 15 weeks, from about 7 weeks to about 15 weeks, from about 8 weeks to about 15 weeks, from about 9 weeks to about 15 weeks, or from about 10 weeks to about 15 weeks.

[0073] In some cases, the method comprises maintain the treatment with respect to dose and administration schedule if the percent change between the first measurement and the second measurement is less than 3% when the second measurement is taken at a time between 14 days and 21 days after the first measurement. In some cases, the method comprises maintain the treatment with respect to dose and administration schedule if the percent change between the first measurement and the second measurement may be less than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5 % when the second measurement is taken at a time between 14 days and 21 days after tire first measurement. In some cases, the method comprises maintain the treatment with respect to dose and administration schedule if the percent change between the first measurement and the second measurement may be less than 20, 19, 18, 17, 16. 15. 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5 % when the second measurement is taken at a time between 1 day to 6 weeks, 1 day to 5 weeks, 1 day to 4 weeks, 1 day to 3 weeks, 1 day to 2 weeks, 1 day to 1 week, 1 week to 6 weeks, 1 week to 5 weeks, 1 week to 4 weeks, 1 week to 3 weeks, 1 week to 2 weeks, 2 weeks to 6 weeks, 2 weeks to 5 weeks, 2 weeks to 4 weeks, 2 weeks to 3 weeks. 3 weeks to 6 weeks, 3 weeks to 5 weeks, or 3 weeks to 4 weeks after the first measurement. In some cases, the method comprises maintain the treatment with respect to dose and administration schedule if the percent change between the first measurement and the second measurement may be less than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5 %.

[0074] In some cases, the method comprises changing the treatment by increasing a dose of the treatment if the percent change between the first measurement and the second measurement is greater than 3% when the second measurement is taken at least 14 days after the first measurement. In some cases, the method comprises changing the treatment by increasing a dose of tire treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1. 2, 3, 4, 5. 6, 7, 8, 9. 10, 15, 20, 25, 30, 35, 40. 45. or 50 % when the second measurement is taken at least 14 days after the first measurement. In some cases, the method comprises changing the treatment by increasing a dose of the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 % when the second measurement is taken at least 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, or 14 days after the first measurement. In some cases, the method comprises changing the treatment by increasing a dose of the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1. 2, 3, 4. 5. 6, 7, 8. 9. 10. 15. 20, 25, 30, 35, 40, 45. or 50 % when the second measurement is taken at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 weeks afterthe first measurement. In some cases, the method comprises changing the treatment by increasing a dose of the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1, 2, 3, 4, 5, 6, 7. 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 %.

[0075] In some cases, the method comprises stopping the treatment if the percent change between the first measurement and the second measurement is greater than 10% when tire second measurement is taken at least 2 weeks after the first measurement. In some cases, the method comprises stopping the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30 , 35, 40, 45, or 50 % when the second measurement is taken at least 2 weeks afterthe first measurement. In some cases, the method comprises stopping the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1. 2, 3, 4, 5. 6, 7, 8, 9. 10. 11, 12, 13, 14, 15, 16, 17, 18. 19, 20, 25, 30 , 35, 40, 45, or 50 % when the second measurement is taken at least 1, 2, 3. 4, 5, 6, 7. 8, 9, 10, 11, 12. 13. or 14 days after the first measurement. In some cases, the method comprises stopping the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30 , 35, 40, 45, or 50 % when the second measurement is taken at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. 16, 17, 18, 19, 20, 24, 28, 30, 32, 36, or 40 weeks after the first measurement. In some cases, the method comprises stopping the treatment if the percent change between the first measurement and the second measurement is greater than at least 0.5. 1, 2, 3. 4. 5, 6, 7. 8. 9, 10, 11, 12.13, 14, 15, 16, 17, 18, 19, 20, 25, 30 , 35, 40, 45, or 50 %.

[0076] FIG. 5 shows subclassification of ZSF-1 rats by HbAlc level and their oxidative stress levels over 12-23 weeks of age. ZSF-1 Lean, ZSF-1 Obese (HbAlc < 6.25%), and ZSF-1 Obese (HbAlc > 6.25%) ratsare shown. The oxidative stress curve was statistically significantly lower for the lean mice compared to the two groups of obese mice. Additionally, the oxidative stress curve was statistically significantly lower for the obese mice with HbAlc < 6.25% compared to tire obese mice with HbAlc > 6.25%.

[0077] In one aspect, the present disclosure provides a method of detecting a metabolic disease marker in a sample. In some embodiments, the present disclosure provides a method of detecting a metabolic disease marker comprising detecting a redox state of the sample.

[0078] In some embodiments, detecting, discovering, determining, and measuring a metabolic disease marker may be used interchangeably and may include quantitative and / or qualitative determinations, including, for example, identifying the protein / gene. determining presence and / or absence of the protein / gene, and quantifying the protein / gene.

[0079] In some embodiments of the method disclosed herein, the detecting of the redox state is performed by a magnetic resonance relaxometry (MRR). Magnetic resonance relaxometry (MRR) is a technique that may be used in nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) to acquire spin-echoes of (predominantly) water content of the cells / tissues. Recent advances in NMR system miniaturization have raised the prospect of applying these techniques in point-of-care diagnostic setting. These include immuno-magnetic labeling based (e.g. tumor cells, tuberculosis and magneto-DNA detection of bacteria) and label-free pMRR detection of various diseases (e.g., oxygenation / oxidation level of the blood and malaria screening).

[0080] In some embodiments of the method disclosed herein, the method further comprises assessing a redox state of the sample from the longitudinal relaxation time and the transverse relaxation time of the sample. In additional embodiments, a composite redox state of a sample descriebd herein may be qualified with a bench- top sized micro magnetic resonance relaxometry (itMRR) system using a T1 (longitudinal relaxation time)-T2 (transverse relaxation time) diagram. In some embodiments of the method disclosed herein, assessing the redox state comprises plotting a magnetic state diagram of a longitudinal relaxation time and a transverse relaxation time. In some embodiments of the method disclosed herein, assessing tire redox state comprises interpreting the state of the sample based on a location of the sample in the diagram. In some embodiments of the method disclosed herein, assessing the redox state comprises plotting a magnetic state diagram of a longitudinal relaxation time and a transverse relaxation time and interpreting tire state of the sample based on a location of the sample in the diagram. In some embodiments of the method disclosed herein, assessing the redox state comprises calculating a ratio of longitudinal relaxation time to transverse relaxation time of the sample. In some embodiments of the method disclosed herein, assessing the redox state comprises comparing the ratio with a predetermined ratio of a reference sample. In some embodiments of the method disclosedherein, assessing the redox state comprises calculating a ratio of longitudinal relaxation time to transverse relaxation time of the sample, and comparing the ratio with a predetermined ratio of a reference sample.

[0081] In some embodiments of the method disclosed herein, a correlation of Ratio A with the metabolic disease marker described herein is 0.9 or less.

[0082] In some embodiments of the method disclosed herein, a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73. 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65. 0.64, 0.63,0.62, 0.61. 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53. 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45. 0.44, 0.43,0.42, 0.41. 0.4, 0.39, 0.38. 0.37, 0.36, 0.35, 0.34, 0.33. 0.32. 0.31, 0.3. 0.29, 0.28, 0.27, 0.26, 0.25. 0.24. 0.23,0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less.

[0083] In some embodiments of the method disclosed herein, a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65,0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47. 0.46, 0.45,0.44, 0.43. 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35. 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27. 0.26, 0.25,0.24, 0.23. 0.22. 0.21, 0.2. 0.19, 0.18, 0.17, 0.16, 0.15. 0.14. 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07. 0.06. or0.05 or less. In some embodiments of the method disclosed herein, a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81,0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61,0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51. 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43. 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36. 0.35, 0.34, 0.33, 0.32, 0.31. 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23. 0.22, 0.21,0.2, 0.19, 0.18, 0.17. 0.16. 0.15. 0.14, 0.13, 0.12, 0.11. 0.1, 0.09, 0.08. 0.07. 0.06, or 0.05 or less.

[0084] In some embodiments of the method disclosed herein, a correlation of Ratio A with the metabolic disease marker described herein is 0.25 or more. In some embodiments of the method disclosed herein, a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7,0.69, 0.68. 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6. 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5,0.49, 0.48. 0.47, 0.46, 0.45, 0.44, 0.43, 0.42. 0.41, 0.4. 0.39, 0.38, 0.37, 0.36, 0.35, 0.34. 0.33, 0.32, 0.31, 0.3,0.29, 0.28. 0.27. 0.26, 0.25, 0.24, 0.23, 0.22. 0.21. 0.2. 0.19. 0.18, 0.17, 0.16, 0.15, 0.14. 0.13. 0.12, 0.11, 0.1,0.09, 0.08, 0.07, 0.06, or 0.05 or more.

[0085] In some embodiments of the method disclosed herein, a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65,0.64, 0.63. 0.62. 0.61. 0.6. 0.59. 0.58, 0.57, 0.56, 0.55. 0.54. 0.53. 0.52, 0.51, 0.5, 0.49, 0.48, 0.47. 0.46. 0.45.0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25,0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or0.05 or more. In some embodiments of the method disclosed herein, a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88. 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81,0.8, 0.79, 0.78, 0.77, 0.76. 0.75, 0.74, 0.73, 0.72, 0.71. 0.7, 0.69, 0.68. 0.67, 0.66, 0.65, 0.64, 0.63. 0.62. 0.61,0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21,0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 ormore

[0086] In some embodiments of the method disclosed herein, a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65. from about 0.05 to about 0.6. from about 0.05 to about 0.55, from about 0.05 to about 0.5. from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65. from about 0.07 to about 0.6. from about 0.07 to about 0.55, from about 0.07 to about 0.5. from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0. 1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2. from about 0.1 to about 0.15. from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7. from about 0.3 to about 0.65. from about 0.3 to about0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, fromabout 0.4 to about 0.65, from about 0.4 to about 0.6. from about 0.4 to about 0.55. from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.In some embodiments of the method disclosed herein, a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65. from about 0.05 to about 0.6. from about 0.05 to about 0.55, from about 0.05 to about 0.5. from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5. from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2. from about 0.1 to about 0.15. from about 0.2 to about 0.95, from about 0.2 to about 0.9. from about 0.2 to about 0.85. from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7. from about 0.3 to about 0.65. from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45. from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, fromabout 0.4 to about 0.65, from about 0.4 to about 0.6. from about 0.4 to about 0.55. from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85. from about 0.05 to about 0.8. from about 0.05 to about 0.75, from about 0.05 to about 0.7. from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7. from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3. from about 0.1 to about 0.25. from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8. from about 0.3 to about 0.75. from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 toabout 0.55, from about 0.4 to about 0.5. from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8. from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0087] In some embodiments of the method disclosed herein, a correlations of Ratio A with the metabolic disease marker described herein, such as any one of HbAlc, Albumin Creatinine Ratio (ACR), blood glucose, kidney fibrogenesis (aSMA), body weight, tissue damage, and CD45, is 1, 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.69, 0.68, 0.67. 0.66, 0.65, 0.64, 0.63, 0.62, 0.61. 0.6, 0.59. 0.58, 0.57, 0.56, 0.55, 0.54, 0.53. 0.52, 0.51, 0.5, 0.49,0.48, 0.47. 0.46, 0.45, 0.44, 0.43, 0.42, 0.41. 0.4, 0.35. 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27. 0.26. 0.25,0.24, 0.23. 0.22. 0.21. 0.2. 0.19. 0.18, 0.17, 0.16, 0.15. 0.14. 0.13. 0.12, 0.11, 0.1, 0.09, 0.08, 0.07. 0.06. or0.05 or less. In some embodiment of the method disclosed herein, a correlations of Ratio A with tire metabolic disease marker described herein is 1, 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, a correlations of Ratio A with the metabolic disease marker described herein is at least 1, 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05. In some embodiments of the method disclosed herein, a correlations of Ratio A with the metabolic disease marker described herein is at most 1, 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07. 0.06, or 0.05. In some embodiment of the method disclosed herein, a correlations of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 1. from about 0.05 to about 0.9, from about 0.05 to about 0.8, from about 0.05 to about 0.7, from about 0.05 to about 0.5, from about 0.05 to about 0.4, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.24, from about 0.05 to about 0.23, from about 0.05 to about 0.22, from about 0.05 to about 0.21, from about 0.05 to about 0.2, from about 0.05 to about 0.19, from about 0.05 to about 0.18, from about 0.05 to about 0.17, from about 0.05 to about 0.16, from about 0.05 to about 0.15, from about 0.05 to about 0.14. from about 0.05 to about 0.13, from about 0.05 to about 0.12, from about 0.05 to about 0.11, from about 0.05 to about 0.1, from about 0. 1 to about 1, from about 0. 1 to about 0.9, from about 0.1 to about 0.8, from about 0. 1 to about 0.7, from about 0.1 to about 0.5, from about 0. 1 to about 0.4, from about 0. 1 to about 0.3, from about 0.1 to about 0.25, from about 0. 1 to about 0.24, from about 0. 1 to about 0.23, from about 0. 1 to about 0.22,from about 0.1 to about 0.21, from about 0. 1 to about 0.2. from about 0. 1 to about 0.19. from about 0. 1 to about 0.18, from about 0. 1 to about 0.17, from about 0. 1 to about 0. 16, from about 0. 1 to about 0. 15, from about 0. 1 to about 0.14, from about 0. 1 to about 0.13, from about 0. 1 to about 0.12, from about 0. 1 to about 0.11, from about 0.15 to about 1, from about 0.15 to about 0.9, from about 0.15 to about 0.8, from about 0.15 to about 0.7. from about 0.15 to about 0.5, from about 0. 15 to about 0.4, from about 0. 15 to about 0.3, from about 0. 15 to about 0.25, from about 0. 15 to about 0.24. from about 0.15 to about 0.23, from about 0. 15 to about 0.22, from about 0.15 to about 0.21, from about 0.15 to about 0.2, from about 0.15 to about 0.19, from about 0.15 to about 0.18, from about 0.15 to about 0.17, from about 0.15 to about 0.16, from about 0.17 to about 1, from about 0.17 to about 0.9, from about 0.17 to about 0.8, from about 0.17 to about 0.7, from about 0.17 to about 0.5, from about 0.17 to about 0.4, from about 0.17 to about 0.3, from about 0.17 to about 0.25, from about 0.17 to about 0.24. from about 0.17 to about 0.23, from about 0.17 to about 0.22, from about 0.17 to about 0.21, from about 0.17 to about 0.2, from about 0.17 to about 0.19, from about 0.17 to about 0.18, from about 0.2 to about 1, from about 0.2 to about 0.9, from about 0.2 to about 0.8, from about 0.2 to about 0.7, from about 0.2 to about 0.5, from about 0.2 to about 0.4, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.2 to about 0.24, from about 0.2 to about 0.23, from about 0.2 to about 0.22, from about 0.2 to about 0.21, from about 0.22 to about 1, from about 0.22 to about 0.9, from about 0.22 to about 0.8, from about 0.22 to about 0.7, from about 0.22 to about 0.5, from about 0.22 to about 0.4, from about 0.22 to about 0.3. from about 0.22 to about 0.25, from about 0.25 to about 1, from about 0.25 to about 0.9, from about 0.25 to about 0.8, from about 0.25 to about 0.7, from about 0.25 to about 0.5, from about 0.25 to about 0.4, from about 0.25 to about 0.3, from about 0.25 to about 0.29, from about 0.25 to about 0.28, from about 0.25 to about 0.27, or from about 0.25 to about 0.26. In some embodiments of tire method disclosed herein, a correlations of Ratio A with the metabolic disease marker described herein is about 2, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2. 1.1, 1, 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.24, 0.23, 0.22, 0.21. 0.2, 0.19, 0.18. 0.17, 0.16, 0.15, 0.14, 0.13. 0.12. 0.11, 0.1. 0.09, 0.08, 0.07, 0.06, 0.05. 0.04. 0.03, 0.02, 0.01, or 0.005.

[0088] In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73,0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53,0.52, 0.51. 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43. 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35. 0.34, 0.33,0.32, 0.31. 0.3, 0.29, 0.28. 0.27, 0.26, 0.25, 0.24, 0.23. 0.22. 0.21, 0.2. 0.19, 0.18, 0.17, 0.16, 0.15. 0.14. 0.13,0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83,0.82, 0.81. 0.8, 0.79, 0.78. 0.77. 0.76, 0.75, 0.74, 0.73. 0.72. 0.71. 0.7. 0.69. 0.68, 0.67, 0.66, 0.65. 0.64. 0.63.0.62, 0.61 , 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43,0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23,0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less.In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation with the metabolic disease marker described herein is 0.95, 0.94. 0.93. 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68,0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48,0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28,0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08,0.07, 0.06. or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75,0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55,0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35,0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17. 0.16, 0.15,0.14, 0.13. 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65,0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45,0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27. 0.26, 0.25,0.24, 0.23. 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15. 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07. 0.06, or0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71,0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51,0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33. 0.32, 0.31,0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21. 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13. 0.12, 0.11,0.1, 0.09, 0.08, 0.07. 0.06. or 0.05 or more. In some embodiments of tire method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5,from about 0.05 to about 0.45. from about 0.05 to about 0.4. from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45. from about 0.07 to about 0.4. from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0. 1 to about 0.55, from about 0. 1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0. 1 to about 0.25, from about 0.1 to about 0.2. from about 0.1 to about 0.15. from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35. from about 0.05 to about 0.3. from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0. 1 to about 0.9, from about 0. 1 to about 0.85, from about 0. 1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4. from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9. from about 0.3 to about 0.85. from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8. from about 0.5 to about 0.75. from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises HbAlc and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, fromabout 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6. from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0. 1 to about 0.55, from about 0. 1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3. from about 0.1 to about 0.25. from about 0.1 to about 0.2. from about 0.1 to about 0.15. from about 0.2 to about 0.95. from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8. from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55. from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8. from about 0.5 to about 0.75, from about 0.5 to about 0.7. from about 0.5 to about 0.65. from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0089] In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation of Ratio A with the metabolic disease marker described herein is 0.95. 0.94. 0.93,0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73,0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53,0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33,0.32, 0.31. 0.3, 0.29, 0.28. 0.27. 0.26, 0.25, 0.24, 0.23. 0.22. 0.21. 0.2. 0.19. 0.18, 0.17, 0.16, 0.15. 0.14. 0.13. 0.12, 0.11 , 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73. 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65. 0.64, 0.63,0.62, 0.61. 0.6, 0.59, 0.58. 0.57, 0.56, 0.55, 0.54, 0.53. 0.52. 0.51, 0.5. 0.49, 0.48, 0.47, 0.46, 0.45. 0.44. 0.43,0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23,0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less.In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87. 0.86, 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79. 0.78, 0.77, 0.76, 0.75, 0.74, 0.73. 0.72, 0.71, 0.7, 0.69,0.68, 0.67. 0.66. 0.65, 0.64, 0.63, 0.62, 0.61. 0.6, 0.59. 0.58. 0.57, 0.56, 0.55, 0.54, 0.53. 0.52. 0.51, 0.5. 0.49,0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29,0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09,0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88. 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81, 0.8. 0.79, 0.78, 0.77, 0.76. 0.75. 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67. 0.66, 0.65, 0.64, 0.63, 0.62. 0.61. 0.6. 0.59. 0.58,0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38,0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18,0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92. 0.91, 0.9, 0.89, 0.88, 0.87. 0.86. 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79. 0.78. 0.77, 0.76, 0.75, 0.74, 0.73. 0.72. 0.71, 0.7. 0.69,0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49,0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29,0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09,0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93. 0.92. 0.91, 0.9. 0.89, 0.88, 0.87, 0.86, 0.85. 0.84. 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77. 0.76. 0.75,0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55,0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35,0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15,0.14, 0.13. 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the methoddisclosed herein, tire metabolic disease marker comprises blood glucose and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodimentsof the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35. from about 0.05 to about 0.3. from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0. 15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35. from about 0.07 to about 0.3. from about 0.07 to about 0.25, from about 0.07 to about 0.2. from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0. 1 to about 0.95, from about 0.1 to about 0.9, from about 0. 1 to about 0.85, from about 0. 1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0. 1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9. from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7. from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45, from about 0.3 to about 0.4. from about 0.3 to about 0.35. from about 0.4 to about 0.95. from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodimentsof the method disclosed herein, the metabolic disease marker comprises blood glucose and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0090] In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71,0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61. 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53. 0.52, 0.51,0.5, 0.49, 0.48, 0.47, 0.46. 0.45, 0.44, 0.43, 0.42, 0.41. 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33. 0.32, 0.31,0.3, 0.29, 0.28, 0.27. 0.26. 0.25. 0.24, 0.23, 0.22, 0.21. 0.2, 0.19. 0.18. 0.17, 0.16, 0.15, 0.14, 0.13. 0.12. 0.11,0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81,0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71. 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63. 0.62, 0.61,0.6, 0.59, 0.58, 0.57, 0.56. 0.55, 0.54, 0.53, 0.52, 0.51. 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43. 0.42, 0.41,0.4, 0.39, 0.38, 0.37. 0.36. 0.35. 0.34, 0.33, 0.32, 0.31. 0.3, 0.29. 0.28. 0.27. 0.26, 0.25, 0.24, 0.23. 0.22. 0.21,0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84. 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76. 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67, 0.66,0.65, 0.64. 0.63. 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56. 0.55. 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48. 0.47. 0.46,0.45, 0.44. 0.43. 0.42. 0.41, 0.4. 0.39, 0.38, 0.37, 0.36. 0.35. 0.34. 0.33, 0.32, 0.31, 0.3, 0.29, 0.28. 0.27. 0.26.0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74. 0.73, 0.72,0.71, 0.7, 0.69, 0.68, 0.67. 0.66, 0.65, 0.64, 0.63, 0.62. 0.61. 0.6, 0.59. 0.58, 0.57, 0.56, 0.55, 0.54. 0.53. 0.52,0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32,0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12,0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of tire method disclosed herein, the metabolic disease marker comprises ACR and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88. 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81, 0.8, 0.79, 0.78, 0.77, 0.76. 0.75, 0.74, 0.73, 0.72, 0.71. 0.7, 0.69, 0.68. 0.67, 0.66, 0.65, 0.64, 0.63. 0.62. 0.61,0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21,0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92. 0.91, 0.9. 0.89, 0.88, 0.87, 0.86,0.85, 0.84. 0.83. 0.82. 0.81, 0.8. 0.79, 0.78, 0.77, 0.76. 0.75. 0.74. 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67. 0.66.0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51 , 0.5, 0.49, 0.48, 0.47, 0.46,0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26,0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0. 1 to about 0.75, from about 0.1 to about 0.7. from about 0.1 to about 0.65. from about 0.1 to about 0.6, from about 0. 1 to about 0.55, from about 0. 1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6. from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4. from about 0.2 to about 0.35. from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7. from about 0.4 to about 0.65. from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7. from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises ACR and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2. from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0. 1 to about 0.95, from about 0.1 to about 0.9. from about 0.1 to about 0.85. from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6. from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0. 1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5. from about 0.2 to about 0.45, from about 0.2 to about 0.4. from about 0.2 to about 0.35. from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6. from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, fromabout 0.6 to about 0.8. from about 0.6 to about 0.75. from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, tire metabolic disease marker comprises ACR and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95. from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85. from about 0.07 to about 0.8. from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6. from about 0.1 to about 0.55. from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0. 1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6. from about 0.2 to about 0.55. from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3. from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9. from about 0.4 to about 0.85. from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6. from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, fromabout 0.6 to about 0.8. from about 0.6 to about 0.75. from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0091] In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of Ratio A with tire metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86. 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79, 0.78. 0.77, 0.76, 0.75, 0.74, 0.73. 0.72, 0.71,0.7, 0.69, 0.68, 0.67. 0.66. 0.65. 0.64, 0.63, 0.62, 0.61. 0.6, 0.59. 0.58. 0.57. 0.56, 0.55, 0.54, 0.53. 0.52. 0.51.0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41 , 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31,0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11,0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88. 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81,0.8, 0.79, 0.78, 0.77. 0.76. 0.75. 0.74, 0.73, 0.72, 0.71. 0.7, 0.69. 0.68. 0.67. 0.66, 0.65, 0.64, 0.63. 0.62. 0.61.0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21,0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92. 0.91, 0.9. 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66,0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46,0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26,0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73,0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53,0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33,0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13,0.12, 0.11. 0.1, 0.09. 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of oxidative stress with the metabolic disease marker descnbed herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36. 0.35. 0.34, 0.33, 0.32, 0.31. 0.3, 0.29, 0.28. 0.27. 0.26, 0.25, 0.24, 0.23. 0.22. 0.21. 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.1 1 , 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84. 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76. 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67, 0.66,0.65, 0.64. 0.63. 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56. 0.55. 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48. 0.47. 0.46,0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26,0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65. from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8. from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4. from about 0.1 to about 0.35. from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9. from about 0.3 to about 0.85. from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5. from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9. from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7. from about 0.6 to about 0.65. from about 0.7 to about 0.95. from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95. from about 0.05 to about 0.9. from about 0.05 to about 0.85, from about 0.05 to about 0.8. from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8. from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4. from about 0.1 to about 0.35. from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9. from about 0.3 to about 0.85. from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5. from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9. from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7. from about 0.6 to about 0.65. from about 0.7 to about 0.95. from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises aSMA and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65. from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75. from about 0.07 to about 0.7. from about 0.07 to about 0.65, from about 0.07 to about 0.6. from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0.1 to about 0.8, from about 0. 1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0. 1 to about 0.55, from about 0. 1 to about 0.5. from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3. from about 0.1 to about 0.25. from about 0.1 to about 0.2, from about 0. 1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8. from about 0.3 to about 0.75. from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5. from about 0.4 to about 0.45. from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0092] In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71,0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61. 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53. 0.52, 0.51,0.5, 0.49, 0.48, 0.47, 0.46. 0.45, 0.44, 0.43, 0.42, 0.41. 0.4, 0.39, 0.38. 0.37, 0.36, 0.35, 0.34, 0.33. 0.32. 0.31,0.3, 0.29, 0.28, 0.27. 0.26. 0.25. 0.24, 0.23, 0.22, 0.21. 0.2, 0.19. 0.18. 0.17. 0.16, 0.15, 0.14, 0.13. 0.12. 0.11.0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81,0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71. 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63. 0.62, 0.61,0.6, 0.59, 0.58, 0.57, 0.56. 0.55, 0.54, 0.53, 0.52, 0.51. 0.5, 0.49, 0.48. 0.47, 0.46, 0.45, 0.44, 0.43. 0.42. 0.41,0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21,0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84. 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76. 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67, 0.66,0.65, 0.64. 0.63. 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56. 0.55. 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48. 0.47. 0.46,0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26,0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91. 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83. 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75. 0.74, 0.73,0.72, 0.71. 0.7, 0.69, 0.68. 0.67, 0.66, 0.65, 0.64, 0.63. 0.62. 0.61, 0.6. 0.59, 0.58, 0.57, 0.56, 0.55. 0.54. 0.53,0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33,0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13,0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein,the metabolic disease marker comprises CD45 and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91 , 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61,0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41,0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31. 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23. 0.22, 0.21,0.2, 0.19, 0.18, 0.17, 0.16. 0.15, 0.14, 0.13, 0.12, 0.11. 0.1, 0.09, 0.08. 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66,0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46,0.45, 0.44. 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36. 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28. 0.27, 0.26,0.25, 0.24. 0.23. 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16. 0.15. 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08. 0.07. 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35. from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0. 1 to about 0.9, from about 0. 1 to about 0.85, from about 0. 1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9. from about 0.2 to about 0.85. from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35. from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0. 1 to about 0.9, from about 0. 1 to about 0.85, from about 0. 1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9. from about 0.2 to about 0.85. from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises CD45 and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15. from about 0.07 to about 0.1. from about 0.1 to about 0.95, from about 0. 1 to about 0.9, from about 0. 1 to about 0.85, from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0. 1 to about 0.55, from about 0. 1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6. from about 0.3 to about 0.55. from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8. from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8. from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0093] In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91 , 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73,0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53,0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33,0.32, 0.31. 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23. 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15. 0.14, 0.13,0.12, 0.11. 0.1, 0.09, 0.08. 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63,0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43,0.42, 0.41. 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33. 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25. 0.24, 0.23,0.22, 0.21. 0.2, 0.19, 0.18. 0.17, 0.16, 0.15, 0.14, 0.13. 0.12. 0.11, 0.1. 0.09, 0.08, 0.07, 0.06, or 0.05 or less.In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69,0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49,0.48, 0.47. 0.46, 0.45, 0.44, 0.43, 0.42, 0.41. 0.4, 0.39. 0.38, 0.37, 0.36, 0.35, 0.34, 0.33. 0.32, 0.31, 0.3, 0.29,0.28, 0.27. 0.26. 0.25, 0.24, 0.23, 0.22, 0.21. 0.2, 0.19. 0.18. 0.17, 0.16, 0.15, 0.14, 0.13. 0.12. 0.11, 0.1. 0.09,0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78,0.77, 0.76. 0.75. 0.74. 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67. 0.66. 0.65, 0.64, 0.63, 0.62. 0.61. 0.6. 0.59. 0.58.0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51 , 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38,0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18,0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92. 0.91. 0.9, 0.89. 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69,0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49,0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29,0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09,0.08, 0.07. 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75,0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55,0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35,0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17. 0.16, 0.15,0.14, 0.13. 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, tire metabolic disease marker comprises body weight and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8. from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9. from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6. from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35. from about 0.05 to about 0.3. from about 0.05 to about 0.25, from about 0.05 to about 0.2. from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2. from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0. 1 to about 0.95, from about 0.1 to about 0.9. from about 0.1 to about 0.85. from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0. 1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7. from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9. from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6. from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises body weight and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9, from about 0.1 to about 0.85, from about 0. 1 to about 0.8, from about 0. 1 to about 0.75, from about 0. 1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8. from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9. from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6. from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0094] In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of Ratio A with the metabolic disease marker described herein is 0.95. 0.94. 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73,0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53,0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33,0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13,0.12, 0.11. 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63,0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43,0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23,0.22, 0.21. 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13. 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less.In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88, 0.87, 0.86, 0.85, 0.84, 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77, 0.76, 0.75, 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49,0.48, 0.47. 0.46. 0.45. 0.44, 0.43, 0.42, 0.41. 0.4, 0.39. 0.38. 0.37. 0.36, 0.35, 0.34, 0.33. 0.32. 0.31, 0.3. 0.29. 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21 , 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.1 1, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or less. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of Ratio A with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92, 0.91, 0.9, 0.89, 0.88. 0.87, 0.86, 0.85, 0.84, 0.83, 0.82. 0.81, 0.8. 0.79, 0.78, 0.77, 0.76. 0.75. 0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68. 0.67. 0.66, 0.65, 0.64, 0.63, 0.62. 0.61. 0.6. 0.59. 0.58,0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38,0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18,0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of oxidative stress with the metabolic disease marker described herein is 0.95, 0.94, 0.93, 0.92. 0.91, 0.9, 0.89, 0.88, 0.87. 0.86. 0.85, 0.84, 0.83, 0.82, 0.81. 0.8, 0.79. 0.78. 0.77, 0.76, 0.75, 0.74, 0.73. 0.72. 0.71, 0.7. 0.69,0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55, 0.54, 0.53, 0.52, 0.51, 0.5, 0.49,0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35, 0.34, 0.33, 0.32, 0.31, 0.3, 0.29,0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15, 0.14, 0.13, 0.12, 0.11, 0.1, 0.09,0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation with the metabolic disease marker described herein is 0.95, 0.94, 0.93. 0.92. 0.91, 0.9. 0.89, 0.88, 0.87, 0.86, 0.85. 0.84. 0.83, 0.82, 0.81, 0.8, 0.79, 0.78, 0.77. 0.76. 0.75,0.74, 0.73, 0.72, 0.71, 0.7, 0.69, 0.68, 0.67, 0.66, 0.65, 0.64, 0.63, 0.62, 0.61, 0.6, 0.59, 0.58, 0.57, 0.56, 0.55,0.54, 0.53, 0.52, 0.51, 0.5, 0.49, 0.48, 0.47, 0.46, 0.45, 0.44, 0.43, 0.42, 0.41, 0.4, 0.39, 0.38, 0.37, 0.36, 0.35,0.34, 0.33, 0.32, 0.31, 0.3, 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, 0.22, 0.21, 0.2, 0.19, 0.18, 0.17, 0.16, 0.15,0.14, 0.13, 0.12, 0.11, 0.1, 0.09, 0.08, 0.07, 0.06, or 0.05 or more. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of Ratio A with the metabolic disease marker described herein is from about 0.05 to about 0.95. from about 0.05 to about 0.9. from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85. from about 0.07 to about 0.8. from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9,from about 0.1 to about 0.85, from about 0. 1 to about 0.8. from about 0. 1 to about 0.75. from about 0. 1 to about 0.7, from about 0. 1 to about 0.65, from about 0. 1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation of oxidative stress with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2. from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85, from about 0.07 to about 0.8, from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0. 1 to about 0.95, fromabout 0.1 to about 0.9. from about 0.1 to about 0.85. from about 0.1 to about 0.8, from about 0.1 to about 0.75, from about 0.1 to about 0.7, from about 0.1 to about 0.65, from about 0.1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0. 1 to about 0.45, from about 0. 1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0. 1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8, from about 0.2 to about 0.75, from about 0.2 to about 0.7. from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5. from about 0.3 to about 0.45, from about 0.3 to about 0.4. from about 0.3 to about 0.35. from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95. In some embodiments of the method disclosed herein, the metabolic disease marker comprises tissue damage and a correlation with the metabolic disease marker described herein is from about 0.05 to about 0.95, from about 0.05 to about 0.9, from about 0.05 to about 0.85, from about 0.05 to about 0.8, from about 0.05 to about 0.75, from about 0.05 to about 0.7, from about 0.05 to about 0.65, from about 0.05 to about 0.6, from about 0.05 to about 0.55, from about 0.05 to about 0.5, from about 0.05 to about 0.45, from about 0.05 to about 0.4, from about 0.05 to about 0.35, from about 0.05 to about 0.3, from about 0.05 to about 0.25, from about 0.05 to about 0.2, from about 0.05 to about 0.15, from about 0.05 to about 0.1, from about 0.07 to about 0.95, from about 0.07 to about 0.9, from about 0.07 to about 0.85. from about 0.07 to about 0.8. from about 0.07 to about 0.75, from about 0.07 to about 0.7, from about 0.07 to about 0.65, from about 0.07 to about 0.6, from about 0.07 to about 0.55, from about 0.07 to about 0.5, from about 0.07 to about 0.45, from about 0.07 to about 0.4, from about 0.07 to about 0.35, from about 0.07 to about 0.3, from about 0.07 to about 0.25, from about 0.07 to about 0.2, from about 0.07 to about 0.15, from about 0.07 to about 0.1, from about 0.1 to about 0.95, from about 0.1 to about 0.9,from about 0.1 to about 0.85, from about 0. 1 to about 0.8. from about 0. 1 to about 0.75. from about 0. 1 to about 0.7, from about 0. 1 to about 0.65, from about 0. 1 to about 0.6, from about 0.1 to about 0.55, from about 0.1 to about 0.5, from about 0.1 to about 0.45, from about 0.1 to about 0.4, from about 0.1 to about 0.35, from about 0.1 to about 0.3, from about 0.1 to about 0.25, from about 0.1 to about 0.2, from about 0.1 to about 0.15, from about 0.2 to about 0.95, from about 0.2 to about 0.9, from about 0.2 to about 0.85, from about 0.2 to about 0.8. from about 0.2 to about 0.75. from about 0.2 to about 0.7, from about 0.2 to about 0.65, from about 0.2 to about 0.6, from about 0.2 to about 0.55, from about 0.2 to about 0.5, from about 0.2 to about 0.45, from about 0.2 to about 0.4, from about 0.2 to about 0.35, from about 0.2 to about 0.3, from about 0.2 to about 0.25, from about 0.3 to about 0.95, from about 0.3 to about 0.9, from about 0.3 to about 0.85, from about 0.3 to about 0.8, from about 0.3 to about 0.75, from about 0.3 to about 0.7, from about 0.3 to about 0.65, from about 0.3 to about 0.6, from about 0.3 to about 0.55, from about 0.3 to about 0.5, from about 0.3 to about 0.45, from about 0.3 to about 0.4, from about 0.3 to about 0.35, from about 0.4 to about 0.95, from about 0.4 to about 0.9, from about 0.4 to about 0.85, from about 0.4 to about 0.8, from about 0.4 to about 0.75, from about 0.4 to about 0.7, from about 0.4 to about 0.65, from about 0.4 to about 0.6, from about 0.4 to about 0.55, from about 0.4 to about 0.5, from about 0.4 to about 0.45, from about 0.5 to about 0.95, from about 0.5 to about 0.9, from about 0.5 to about 0.85, from about 0.5 to about 0.8, from about 0.5 to about 0.75, from about 0.5 to about 0.7, from about 0.5 to about 0.65, from about 0.5 to about 0.6, from about 0.5 to about 0.55, from about 0.6 to about 0.95, from about 0.6 to about 0.9, from about 0.6 to about 0.85, from about 0.6 to about 0.8, from about 0.6 to about 0.75, from about 0.6 to about 0.7, from about 0.6 to about 0.65, from about 0.7 to about 0.95, from about 0.7 to about 0.9, from about 0.7 to about 0.85, from about 0.7 to about 0.8, from about 0.7 to about 0.75, from about 0.8 to about 0.95, from about 0.8 to about 0.9, from about 0.8 to about 0.85, from about 0.8 to about 0.95, or from about 0.9 to about 0.95.

[0095] In some embodiments of the method disclosed herein, the method further comprises obtaining a sample from a subject. In additional embodiments, the subject may be a mammalian subject. The mammalian subject may be an equine, feline, canine, bovine or porcine animal. The subject may be a human.

[0096] In some embodiments of the method disclosed herein, the sample comprises at least one selected from the group consisting of whole blood, serum, plasma, urine, saliva, sweat, fecal matter, and tears of a subject. In some embodiments of the method disclosed herein, the sample comprises a blood sample. In some embodiments of the method disclosed herein, the blood sample is plasma. In some embodiments of the method disclosed herein, the blood sample is red blood cells. In some embodiments, tire sample may be body fluid, tissue, or cell sample. In some embodiments, the body fluid may be blood, sweat, or urine. In some embodiments, the blood sample may be plasma, serum, or red blood cells. In some embodiments, the method may be used to monitor acute or chronic oxidative stress.

[0097] In some embodiments of the method disclosed herein, the sample may be cryopreserved. In some embodiments of the method disclosed herein, the sample may be cryopreserved at -80°C. In some embodiments of the method disclosed herein, the sample may not be cry opreserved. In some embodiments, the cryopreserved sample may be thawed at 4 °C. In some embodiments, the cryopreserved sample may be thawed at 37 °C. In some embodiments, the cryopreserved sample may be thawed at room temperature.

[0098] In some embodiments of the method disclosed herein, an amount of sample is at least 0.1. 0.2, 0.3, 0.4, 0.5. 0.6. 0.7, 0.8, 0.9, 1. 1.5. 2, 2.5, 3, 3.5. 4, 4.5, 5, 5.5. 6, 6.5, 7, 7.5. 8. 8.5, 9, 9.5, or 10 pL. In some embodiments of the method disclosed herein, an amount of sample is at most 30, 25, 20, 15, 10, 9.5, 9, 8.5, 8,7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5 pL. In some embodiments of the method disclosed herein, an amount of sample is from about 0. 1 to about 20, from about 0.1 to about 15, from about 0. 1 to about 10, from about 0.1 to about 9.5, from about 0.1 to about 9, from about 0.1 to about 8.5, from about 0.1 to about 8. from about 0. 1 to about 7.5, from about 0. 1 to about 7, from about 0.1 to about 6.5, from about 0.1 to about 6. from about 0. 1 to about 5.5, from about 0. 1 to about 5. from about 0.1 to about 4.5, from about 0.1 to about 4, from about 0. 1 to about 3.5, from about 0. 1 to about 3, from about 0.1 to about 2.5, from about 0.1 to about 2, from about 0.1 to about 1.5, from about 0.1 to about 1, from about 0.1 to about 0.5, from about 0.5 to about 20, from about 0.5 to about 15, from about 0.5 to about 10, from about 0.5 to about 9.5, from about 0.5 to about 9, from about 0.5 to about 8.5, from about 0.5 to about 8, from about 0.5 to about 7.5. from about0.5 to about 7. from about 0.5 to about 6.5, from about 0.5 to about 6, from about 0.5 to about 5.5. from about0.5 to about 5. from about 0.5 to about 4.5, from about 0.5 to about 4, from about 0.5 to about 3.5. from about0.5 to about 3, from about 0.5 to about 2.5, from about 0.5 to about 2, from about 0.5 to about 1 .5, from about0.5 to about 1, from about 1 to about 20, from about 1 to about 15, from about 1 to about 10, from about 1 to about 9.5, from about 1 to about 9, from about 1 to about 8.5, from about 1 to about 8, from about 1 to about7.5, from about 1 to about 7, from about 1 to about 6.5, from about 1 to about 6, from about 1 to about 5.5, from about 1 to about 5, from about 1 to about 4.5, from about 1 to about 4, from about 1 to about 3.5, from about 1 to about 3, from about 1 to about 2.5, from about 1 to about 2. from about 3 to about 20. from about 3 to about 15, from about 3 to about 10, from about 3 to about 9.5, from about 3 to about 9, from about 3 to about 8.5, from about 3 to about 8, from about 3 to about 7.5, from about 3 to about 7, from about 3 to about6.5, from about 3 to about 6, from about 3 to about 5.5, from about 5 to about 20, from about 5 to about 15, from about 5 to about 10, from about 5 to about 9.5, from about 5 to about 9, from about 5 to about 8.5, from about 5 to about 8, from about 5 to about 7.5, from about 5 to about 7. or from about 5 to about 6.5 pL.

[0099] In some embodiments, the sample may be diluted and incubated with hydrogen peroxide. In some embodiments, the hydrogen peroxide may be 30-50% stock solution. In some embodiments, the hydrogen peroxide may be diluted with distilled water. In some embodiments, the diluted hydrogen peroxide may be incubated with a sample. In some embodiments, the diluted hydrogen peroxide may be incubated with asample at room temperature. In some embodiments, the diluted hydrogen peroxide may be incubated with a sample at 0, 4, 10, 15, 18, 20, 25, 26, 28, 30, 35, 40, 45, 50, or 55 °C or more. In some embodiments, the diluted hydrogen peroxide may be incubated with a sample at 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 5, 4, 3, 1, or 0 °C or less.

[0100] In some embodiments of the method disclosed herein, the subject may have a metabolic disease. In some embodiments of the method disclosed herein, the subject may bave a risk of metabolic disease. In some embodiments of the method disclosed herein, the subject may be diagnosed with a metabolic disease.

[0101] In some embodiments of the method disclosed herein, a Ratio A, a ratio, ratio-a, a-ratio may be used interchangeably. In some embodiments of the method disclosed herein, Ratio A is a ratio of Ti and T2 (T1 / T2).

[0102] In another aspect, the present disclosure also provides a method of identifying a risk for a metabolic disease in a subject. In some embodiments of the method disclosed herein, the method of identifying a risk for metabolic disease in a subject comprises detecting a redox state of the sample described herein.

[0103] In another aspect, the present disclosure also provides a method of monitoring a status of a metabolic disease in a subject in need thereof. In some embodiments of the method disclosed herein, the method of monitoring a status of a metabolic disease in a subject in need thereof comprises detecting a metabolic disease marker described herein.

[0104] In another aspect, the present disclosure also provides a method of diagnosing a metabolic disease in a sample. In some embodiments of the method disclosed herein, the method comprises detecting a metabolic disease marker described herein.

[0105] In another aspect, the present disclosure also provides a method of treating a metabolic disease in a subject in need thereof. In some embodiments of the method disclosed herein, the method of treating a metabolic disease in a subject in need thereof comprises detecting or monitoring a metabolic disease marker or diagnosing a metabolic disease in the subject as described herein, and treating the metabolic disease in the subject.

[0106] In some embodiments of the method disclosed herein, the detection of a redox state comprises measuring a longitudinal relaxation time (Ij ) and a transverse relaxation time (T2) in the sample. In some embodiments of the method disclosed herein, the redox state is a level of oxidative stress. In some embodiments of the method disclosed herein, the redox state is a level of oxidative stress of hemoglobin. In some embodiments of the method disclosed herein, the redox state is a level of nitrosative stress of hemoglobin.

[0107] In some embodiments, the method rapidly quantifies the composite redox state of the hemoglobin / plasma with a micro magnetic resonance relaxometry (pN MR) system using longitudinal relaxation time (Ti) and transverse relaxation time (T2).

[0108] In some embodiments, a magnetic state diagram for assessing redox state of a sample may include a two-dimensional plot of a longitudinal relaxation time and transverse relaxation time.

[0109] In some embodiments, assessment of the oxidative status by measuring the redox state of the blood may be shown to be highly time- and patient-specific, potentially unlocking information that is critical for clinical diagnostic, monitoring and prognostic purposes.

[0110] In some embodiments, the measurement of redox properties in plasma / erythrocytes may provide a useful parameter for functional phenotyping of many biological pathways leading to the understanding of diseases onset / progression and hence its application to disease diagnosis, prognosis and monitoring.[OH l] In some embodiments, a magnetic resonance relaxometry device may be include a radio-frequency spectrometer comprising at least one field-programmable gate array chip, a power amplifier electrically connected with the radio-frequency spectrometer and amplifying an electrical output of the radio-frequency spectrometer, thereby producing an amplified electrical signal comprising between about 0. 1 Watts and about 10 Watts of power, a duplexer configured to isolate the radio-frequency spectrometer from the amplified electrical signal during a receiving mode of the device, a radio-frequency detection probe configured to transmit radio-frequency electromagnetic radiation to excite nuclei under resonance during a transmission mode of the device, the radio-frequency detection probe comprising a detection coil comprising an inner diameter of less than about 1 millimeter, and at least one magnet supplying an external magnetic field to a detection region of the radio-frequency detection probe, the external magnetic field being less than about 3 Tesla. Alternatively, the magnetic resonance relaxometry device can include conventional NMR spectroscopy using higher external magnetic field higher than about 3 Tesla.

[0112] This highly sensitive and targeted approach (as well as composite measurement) may accurately detect and quantify the redox (and hence oxidative / nitrosative) state of blood samples. The non-destructive nature of the MRR measurement may allow oxidative stress to be artificially introduced in an ex vivo environment using different biochemical compounds (c.g., nitrite, peroxide, sodium salicylic) in a controlled manner to the cells. This may allow functional assessment of the oxidative susceptibility, tolerance and capacity of a subject. This may yield richer and clinically useful information about the oxidative health of an individual, which is difficult to achieve with the routine biomarkers. A T1-T2 magnetic state diagram may be developed to enumerate the various redox states of the Hb (e g., Fe2+, Fe3+, Fe4+, and globin-associated radical Fe4+) and plasma. This state diagram may allow visualization and identification of the intermediate redox states and the transient dynamic pathways of the blood.EXAMPLES

[0113] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.Example 1: Diabetes Disease Profiling with Oxidative Stress Assay

[0114] A pNMR assay was developed to monitor oxidative stress in subjects with diabetes from minimally invasive plasma samples at the point of care. This approach may be sensitive to redox changes in the blood microenvironment, including increased ferric ion (Fe3+). protein oxidation, and lipid peroxidation. It was hypothesized that oxidative stress would increase significantly faster in the disease group, enabling disease progression monitoring throughout the study and near real-time subject risk stratification based on the core pathophysiology of the diabetic phenotype. This 15 -week longitudinal study (6th- 21stweek of age) quantified oxidative stress in db / db (diabetic) and db / + (control) mice (n = 15 per group), accompanied by HbAic, blood glucose (BG), and body weight (BW). The assay detailed separation (P < 0.01) between the db / db and db mice from the onset of the diabetic phenotype of db db at 10 weeks of age (mean HbAic= 8.8%). The definition of good (HbAic< 8) and poor (HbAic> 8) glycemic control was defined where substratification (P < 0.05) was achieved. The assay furthermore found a positive correlation between oxidative stress and BW (p+,a> = 0.52, P < 0.0001, p* / * = 0.57, P < 0.0001). In the two groups of mice, a positive correlation of oxidative stress with HbAic(p = 0.58, P < 0.0001) and BG (p = 0.47, P < 0.0001) was observed. During the 15-week study, the control db group exhibited a 13% mean increase in oxidative stress. By contrast, the db / db group demonstrated a cumulative 20% increase. Notably, considering the diabetic phenotype of the db db mice, oxidative stress attributed to aging was quantified at 13%. In view of changing diabetes demographics, a multimodal approach of targeted sub-phenotype treatment combined with advanced metabolic monitoring may provide holistic, clinically relevant information to reduce the micro and macro vascular burden of diabetes.

[0115] Table 1 shows results for db / + control mice. At each age (6 weeks, 9 weeks, 10 weeks, 12 weeks. 14 weeks, 16 weeks, 19 weeks, and 21 weeks), the mean oxidative stress level (ratio of T1 to T2 relaxation times) for the group of mice, the standard deviation of the oxidative stress levels for that group, the number of subjects N, the percent change in mean oxidative stress levels between each time point, the absolute change in mean oxidative stress levels between each time point, the mean HbAic, and the mean body weight are shown.Table 1. Results for db / + control mice.

[0116] Table 2 shows results for db'db diabetic mice. At each age (6 weeks, 9 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks. 19 weeks, and 21 weeks), the mean oxidative stress level (ratio of T1 to T2 relaxation times) for the group of mice, the standard deviation of the oxidative stress levels for that group, the number of subjects N, the percent change in mean oxidative stress levels between each time point, the absolute change in mean oxidative stress levels between each time point, the mean HbAlC, and the mean body weight are shown.Table 2. Results for db / db diabetic mice.

[0117] By comparing Table 1 and Table 2, it can be seen that at 10 weeks, the mean oxidative stress was significantly higher for the db / db mice compared to the db / + mice. Although oxidative stress increases over the lifetime, mean oxidative stress increased more and stayed higher for db / db mice compared to db / + mice. This can be observed in FIG. 14.

[0118] FIG 14 shows a graph of oxidative stress, HbAlc, and ACR over time (at 12 weeks, 15 weeks, 19 weeks, and 23 weeks) in groups of lean mice, obese untreated mice, and obese mice treated with GLP-1. Theleftmost graph shows that although oxidative stress increased with age for all three groups of mice, obese mice had higher oxidative stress levels than lean mice. Oxidative stress levels were decreased for obese mice treated with GLP-1. The middle graph shows that obese mice had higher HbAlc than lean mice, with HbAlc lower for obese mice treated with GLP-1. Tire rightmost graph show s that obese mice had higher ACR than lean mice, with ACR lower for obese mice treated w ith GLP-1.

[0119] FIG. 16 illustrates a quantitative relationship between age and oxidative stress in db / db diabetic and + / db control mice. It was found that although oxidative stress increases with age for both diabetic and control mice, diabetic mice have higher levels of oxidative stress than control mice between 10 and 23 weeks of age. For db / db diabetic mice, tire quantitative relationship between oxidative stress and age w as:OxStress — 0.022 * Age(weeks) + 1.62For + / db control mice, the quantitative relationship between oxidative stress and age was:OxStress = 0.014 * Age weeks) + 1.65Example 2: Diabetes Drug Screening with Oxidative Stress Assay

[0120] In this example, oxidative stress profiling of three groups of ZSF-1 rats in a twelve week (11th- 23rdweek of age) observational study was shown. Vehicle lean, vehicle obese, and glucagon-like -peptide -1 (GLP- 1) treated obese ZSF-1 rats (n=8 / group) were studied with the assay along with conventional diabetic / metabolic markers, blood glucose (BG), HbAlc, and Albumin Creatinine Ratio (ACR). Kidney (immune)histology studies, alpha-smooth muscle actin (aSMA) assays, and leucocyte common antigen (CD45) assays were performed at the termination phase of the ZSF-1 rats (23rdweek of age). Tire results demonstrated that the assay distinguished obese rats from lean rats with statistical significance (P < 0.01) independent of other in-life diabetic / metabolic markers. Significant correlations with urinary Albumin Creatinine Ratio (ACR, p = 0.64, P < 0.0001) were established throughout the study. A positive quantitative association was highlighted with classic histological end points of organ damage, kidney fibrogenesis (aSMA, p = 0.23), and inflammation (CD45, p = 0.45). Moreover, the assay detected significantly reduced oxidative stress levels (e.g., P < 0.01) in tire GLP-1 drug treatment group at five weeks of follow-up. Tire pNMR assay effectively monitored oxidative stress and captured disease-modifying therapeutics.

[0121] FIG. 6 shows significant differences in oxidative stress levels (T1 / T2 ratio), between ZSF-1 control rats, ZSF-1 untreated obese rats, and ZSF-1 obese rats treated with GLP-1 medication at 19 weeks old. The difference in average oxidative stress levels between the ZSF-1 control rats and the ZSF-1 untreated obese rats was significant at the p < 0.0001 level. The difference in average oxidative stress levels between the ZSF- 1 untreated obese rats and the ZSF-1 GLP-1 treated obese rats was significant at the p < 0.01 level.

[0122] FIG. 7 shows albumin creatinine ratio (ACR) vs. oxidative stress level (T1 / T2 ratio) for ZSF-1 control rats, ZSF-1 untreated obese rats, and ZSF-1 obese rats treated with GLP-1 medication. This wasperfonned on mice between 12 weeks and 23 weeks of age. Significant differences at the p < 0.0001 level were seen between the three groups. The p value was 0.59. The ZSF-1 lean model maintained relatively low ACR levels. The ZSF-1 lean model oxidative stress levels increased over time, indicating that whatever damage is occurring to the lean model was not picked up by the ACR itself. The lean group was stratified over time, showing disease progression even on the lean group. The ZSF-1 obese group showed that when administered a GLP-1 analogue, the ZSF-1 treated obese group had lower ACR and lower oxidative stress when compared to the obese control, which had higher ACR and higher oxidative stress. Damage from chronic kidney disease did not show up in the lean control, but the lean control showed progression on oxidative stress, which is linked to other complications, e.g., hypertension. The damage linking oxidative stress to kidney damage showed up on the GLP-1 treated obese and the control obese rats.

[0123] FIG. 8 shows graphs of oxidative stress (T1 / T2 ratio), HbAlc, and ACR over time (at 12 weeks, 1 weeks, 17 weeks, and 19 weeks) in groups of ZSF-1 lean rats. ZSF-1 untreated obese rats, and drug #l-treated ZSF-1 obese rats. With drug #1, differences in oxidative stress level between untreated obese and treated obese were small. The HbAlc difference between untreated obese and treated obese at 19 weeks was significant but also small. Hie ACR was significantly increased at 19 weeks for drug treatment compared to untreated obese rats and lean rats.

[0124] FIG. 9 shows graphs of oxidative stress (T1 / T2 ratio), HbAlc, and ACR overtime (at 12 weeks, 15 weeks, 17 weeks, and 19 weeks) in groups of ZSF-1 lean rats, ZSF-1 untreated obese rats, and drug #2-treated ZSF-1 obese rats. With drug #2, drug-treated obese rats saw a significant decrease in oxidative stress levels by 19 weeks compared to untreated obese rats. Both were still higher than lean rats. This correlated with lower HbAlc and ACR values for drug treatment as well.

[0125] FIG. 10 shows graphs of oxidative stress (T1 / T2 ratio), HbAlc. and ACR over time (at 12 weeks, 15 weeks, 17 weeks, and 19 weeks) in groups of ZSF-1 lean, ZSF-1 untreated obese, and drug #3-treated ZSF-1 obese rats. With drug #3, drug-treated obese rats saw a significant decrease in oxidative stress levels by 19 weeks compared to untreated obese rats. Both were still higher than lean rats. This correlated with low er HbAlc and ACR values for drug treatment as well.

[0126] FIG. 11 shows graphs of oxidative stress. HbAlc, and ACR over time (at 12 weeks, 15 weeks, 17 weeks, and 19 weeks) in groups of ZSF-1 lean, ZSF-1 untreated obese, and drug #4-treated ZSF-1 obese rats. With drug #4, differences in oxidative stress level between untreated obese and treated obese were small. The HbAlc difference between untreated obese and treated obese at 19 weeks was likely significant, but also small. The ACR was significantly decreased at 19 weeks for drug treatment compared to untreated obese rats and lean rats.

[0127] FIG. 15 illustrates a quantitative relationship between age and oxidative stress in ZSF-1 lean and ZSF-1 obese rats. It was found that although oxidative stress increases with age for both lean and obese rats.obese rats have higher levels of oxidative stress than lean rats between 12 and 23 weeks of age. For ZSF-1 obese rats, the quantitative relationship between oxidative stress and age was:OxStress = 0.026 * Age(weeks) + 1.94For ZSF-1 lean rats, tire quantitative relationship between oxidative stress and age was:OxStress = 0.025 * Age (weeks) + 1.79

[0128] Table 3 shows results for ZSF-1 lean rats. At each age (12 weeks, 15 weeks, 17 weeks, 19 weeks, 21 weeks, and 23 weeks), the mean oxidative stress level for the group of rats, the standard deviation of the oxidative stress levels for that group, the number of subjects N, the percent change in mean oxidative stress levels between each time point, the absolute change in mean oxidative stress levels between each time point, the mean HbAlC. the mean ACR. the mean body weight, and a comparison between mean oxidative stress for obese rats vs. lean rats at each time point (Table 4) are shown.Table 3. Results for ZSF-1 lean rats.

[0129] Table 4 shows results for ZSF-1 obese rats (untreated). At each age (12 weeks, 15 weeks. 17 weeks, 19 weeks, 21 weeks, and 23 weeks), the mean oxidative stress level level (ratio of T1 to T2 relaxation times) for the group of rats, tire standard deviation of the oxidative stress levels for that group, the number of subjects N, the percent change in mean oxidative stress levels between each time point, the absolute change in mean oxidative stress levels between each time point, the mean HbAlC, the mean ACR, and the mean body weight are shown.Table 4. Results for ZSF-1 obese rats (untreated).Weeks Mean : SD N % change abs. BWold Oxidativ changeStress

[0130] Table 5 shows results for ZSF-1 obese rats treated with GLP-1. At each age (12 weeks, 15 weeks. 17 weeks, 19 weeks, 21 weeks, and 23 weeks), the mean oxidative stress level (ratio of T1 to T2 relaxation times) for the group of rats, the standard deviation of the oxidative stress levels for that group, the number of subjects N, the percent change in mean oxidative stress levels between each time point, the absolute change in mean oxidative stress levels between each time point, the mean HbAlC, the mean ACR, and the mean body weight are shown.

[0131] Table 5. Results for ZSF-1 obese rats treated with GLP-1.

[0132] Overall, oxidative stress levels, as measured by T 1 / T2 ratio, for example, seemed to correlate highly with HbAlc and ACR levels with treatment with drugs that appear to be more effective on HbAlc and ACR levels (drugs #2 and #3). For drugs #1 and #4. where the effects of drug treatment on HbAlc and ACR were smaller or unclear, oxidative stress levels did not show major differences between treatment and control groups. This may demonstrate that drugs #1 and #4 have negative side effects, as evidenced by a lack of decrease in oxidative stress levels, despite some improvement in HbAlc and ACR markers.

[0133] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0134] EmbodimentsEmbodiment 1 . A method for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said method comprising: a. obtaining a plasma or blood sample from said subject, wherein said subject has been treated with one or more therapies or treatments for said metabolic disorder; b. applying a micro-scale nuclear magnetic resonance (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c. periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d. evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject and determine effectiveness of said one or more therapies or treatments.Embodiment 2. The method of embodiment 1, wherein said blood sample is a red blood cell (RBC) sample.Embodiment 3. Tire method of embodiment 1 or 2, wherein said oxidative stress measurement is calculated as a ratio between a longitudinal proton magnetic resonance relaxation time measurement and a transverse proton magnetic resonance relaxation time measurement of said plasma or blood sample.Embodiment 4. The method of any one of embodiments 1 to 3, wherein said one or more therapies or treatments for said metabolic disorder are selected from a group comprising a GLP-1 agonist, a biguanide, a meglitinide, an alpha-glucosidase inhibitor, a thiazolidinedione, a DPP-4 inhibitor, a sulfonylurea, a dopamine receptor agonist, a bile acid sequestrant, an SGLT2 inhibitor, a combination medicine, incretin, an incretin derivative, an ACE inhibitor, insulin, an insulin derivative, an amylin analog, and peptide YY.Embodiment 5. The method of embodiment 4, wherein said GLP-1 agonist is dulaglutide, exenatide, exenatide extended-release, liraglutide, lixisenatide, semaglutide injection, semaglutide tablets, or tirzepatide.Embodiment 6. Tire method of embodiment 4, wherein said biguanide is metformin.Embodiment 7. The method of embodiment 4, wherein said one or more therapies or treatments is a control therapy or treatment.Embodiment 8. Tire method of any one of embodiments 1 to 7, wherein said plurality of oxidative stress measurements is used to identify side effects of said one or more therapies or treatments.Embodiment 9. The method of any one of embodiments 1 to 8, wherein an initial oxidative stress level is measured in said subject and used to identify whether said subject is suffering from a metabolic disorder or disease.Embodiment 10. Hie method of any one of embodiments 1 to 9, wherein said oxidative stress measurement is generated by analyzing one or more T1 relaxation times and one or more T2 relaxation times of said plasma or blood sample for said subject.Embodiment 11. The method of embodiment 10, wherein said one or more T1 relaxation times and said one or more T2 relaxation times are generated using a micro-scale nuclear magnetic resonance (pNMR) device.Embodiment 12. The method of any one of embodiments 1 to 11, wherein said plurality of plasma or blood samples is collected periodically every week over a period of 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, or 20 weeks.Embodiment 13. The method of any one of embodiments 1 to 12, wherein said plurality of oxidative stress measurements is ordered longitudinally to monitor disease progression and treatment effectiveness in said subject overtime.Embodiment 14. Hie method of any one of embodiments 1 to 13, wherein said plurality of plasma or blood samples is obtained in a minimally invasive manner.Embodiment 15. The method of any one of embodiments 1 to 14, wherein said plurality of plasma or blood samples is obtained at a point-of-care location.Embodiment 16. Hie method of any one of embodiments 1 to 15, wherein said pNMR assay comprises detection of redox changes in said plurality of plasma or blood samples.Embodiment 17. The method of embodiment 16, wherein said redox changes comprise one or more of increased ferric ion content, increased protein oxidation, or increased lipid peroxidation.Embodiment 18. The method of any one of embodiments 1 to 17, further comprise or ng repeating steps (a) to (d) for a plurality of subjects.Embodiment 19. The method of any one of embodiments 1 to 18, wherein said plurality of oxidative stress measurements is compared between a plurality of subjects with said metabolic disorder and a plurality of subjects without said metabolic disorder.Embodiment 20. The method of any one of embodiments 1 to 19, wherein results from said pNMR assay are evaluated alongside other diabetic markers or metabolic markers, said diabetic markers or metabolic markers comprising one or more of blood glucose, ElbAlc, or albumin creatinine ratio, for said subject or said plurality of subjects.Embodiment 21. The method of any one of embodiments 1 to 20, wherein results from said pNMR assay allow for real-time subject risk stratification.Embodiment 22. The method of any one of embodiments 1 to 21, wherein results from said pNMR assay are used for cardiometabolic risk assessment.Embodiment 23. The method of any one of embodiments 1 to 22, wherein said method is used to evaluate oxidative stress in mice.Embodiment 24. The method of any one of embodiments 1 to 23, wherein said method is used to evaluate oxidative stress levels in one or more of lean mice, obese mice, ob / ob mice, diabetic mice, or db / db mice treated with said one or more therapies or treatments.Embodiment 25. The method of any one of embodiments 1 to 24, wherein said method is used to evaluate oxidative stress levels in ZSF-1 rats.Embodiment 26. Hie method of any one of embodiments 1 to 25, wherein said method is used to evaluate oxidative stress levels in one or more subjects in an observational study.Embodiment 27. The method of any one of embodiments 1 to 26, wherein said method is used to evaluate one or more effects of said one or more therapies or treatments on oxidative stress levels in mice.Embodiment 28. The method of any one of embodiments 1 to 27, wherein said method is used to evaluate one or more effects of said one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes, obesity, or diabetic kidney disease.Embodiment 29. The method of any one of embodiments 1 to 28, wherein said method is used to evaluate oxidative stress levels in leptin-deficient mice.Embodiment 30. The method of any one of embodiments 1 to 29, wherein said method is used to evaluate oxidative stress levels in ZSF-1 rats.Embodiment 31. Hie method of any one of embodiments 1 to 30, wherein said metabolic disorder comprises pre-diabetes, diabetes, or diabetic kidney disease.Embodiment 32. A method of treating a subject suffering from a metabolic disorder, said method comprising administering to said subject a metabolic disorder therapy, i.wherein said subject has been determined to be responsive to said metabolic disorder therapy via results from a pNMR assay that measures said subject's oxidative stress levels from one or more plasma or blood samples of said subject.Embodiment 33. The method of embodiment 32, said method comprising: a. collecting a first oxidative stress measurement in said subject undergoing a first treatment for a metabolic disorder or disease; b. at a later time from (a), collecting a second oxidative stress measurement for said subject; and c. comparing said first oxidative stress measurement and said second oxidative stress measurement to determine a percent change in oxidative stress for said subject.Embodiment 34. The method of embodiment 33, wherein said second oxidative stress measurement is collected 2-8 weeks after said first oxidative stress measurement.Embodiment 35. Tire method of embodiment 33 or 34. wherein if said percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than a threshold, a change in treatment protocol for said subject is made.Embodiment 36. The method of embodiment 33 or 34. wherein if said percent change in oxidative stress for the subject deviates from a standard age-related progression of oxidative stress for that subject’s species by greater than 2%, a change in treatment protocol for said subject is made.Embodiment 37. Tire method of embodiment 35 or 36, wherein said change in treatment protocol is stopping said first treatment and starting a second treatment different from said first treatment.Embodiment 38. The method of embodiment 35 or 36, wherein said change in treatment protocol is increasing a dose of said first treatment.Embodiment 39. Hie method of embodiment 33 or 34, wherein if said percent change in oxidative stress for said subject deviates from a standard age-related progression of oxidative stress for that subject’s species by less than 2%, said first treatment is maintained for said subject.Embodiment 40. The method of embodiment 33 or 34, wherein if said percent change in oxidative stress for said subject deviates from a standard age-related progression of oxidative stress for that subject's species by less than a threshold, said first treatment is maintained for said subject.Embodiment 41 . The method of embodiment 32, wherein said subject has been determined to be responsive to said metabolic disorder therapy by the method of any one of embodiments 1 to 31.Embodiment 42. A system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said system comprising: a. a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples: b. a processor; and c. a memory coupled to said processor and having instructions for said processor to perform any one of the methods of embodiments 1 to 41.Embodiment 43. A system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said system comprising: a. a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; b. a processor; andc. a memory coupled to said processor and having instructions for said processor to: i. determine oxidative stress measurements based on said pNMR-based assays conducted on said plurality of plasma or blood samples, ii. store said determined oxidative stress measurements, and iii.order said determined oxidative stress measurements longitudinally, wherein one or more of disease progression or effectiveness of said one or more therapies or treatments for said metabolic disorder is determined based on said determined oxidative stress measurements that are ordered longitudinally.Embodiment 44. The system of embodiment 43, wherein said plurality of plasma or blood samples is collected from one or more test mice.Embodiment 45. The system of embodiment 43, wherein said plurality of plasma or blood samples is collected from one or more test rats.Embodiment 46. The system of embodiment 42 or 43, wherein said plurality of plasma or blood samples is collected at regular intervals.Embodiment 47. The system of any one of embodiments 42 to 46, wherein said pNMR-based assays detect redox changes in said plurality of plasma or blood samples.Embodiment 48. The system of embodiment 47, wherein said redox changes comprise one or more of increased ferric ion content, increased protein oxidation, or increased lipid peroxidation.Embodiment 49. The system of any one of embodiments 42 to 48, wherein said determined oxidative stress measurements are compared between a plurality of subjects with said metabolic disorder and a plurality of subjects without said metabolic disorder.Embodiment 50. Hie system of any one of embodiments 42 to 49, wherein results from said pNMR- based assays allow for real-time subject risk stratification.Embodiment 1. The system of any one of embodiments 42 to 50, wherein results from said pNMR- based assays are used for cardiometabolic risk assessment.Embodiment 52. Tire system of any one of embodiments 42 to 51, wherein said system is used to evaluate one or more effects of said one or more therapies or treatments on oxidative stress levels in one or more subjects with diabetes.Embodiment 53. The system of any one of embodiments 42 to 52, wherein said metabolic disorder comprises pre-diabetes, diabetes, or diabetic kidney disease.Embodiment 54. A method for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having said disorder or disease, said method comprising: a. obtaining a plasma or blood sample from said subject, wherein said subject has been treated with one or more therapies or treatments for said disorder or disease; b. applying a micro-scale magnetic resonance relaxometry (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c. periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d. evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject and determine effectiveness of said one or more therapies or treatments.Embodiment 55. A method of treating a subject suffering from a disorder or disease, said method comprising administering to said subject a therapy or treatment for said disorder or disease, wherein said subject has been determined to be responsive to said therapy or treatment via results from a micro-scale nuclear magnetic resonance assay that measures said subject’s oxidative stress levels from one or more plasma or blood samples of said subject.Embodiment 56. A system for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having said disorder or disease, said system comprising: a. a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; b. a processor; and c. a memory coupled to said processor and having instructions for said processor to: i. determine oxidative stress measurements based on said pNMR-based assays conducted on said plurality of plasma or blood samples, ii. store said determined oxidative stress measurements, andiii. order said determined oxidative stress measurements longitudinally. wherein one or more of disease progression or effectiveness of said one or more therapies or treatments for said disorder or disease are determined based on said determined oxidative stress measurements that are ordered longitudinally.Embodiment 57. A method for monitoring disease progression in a subject with or at risk of having a metabolic disorder, said method comprising: a. obtaining a plasma or blood sample from said subject; b. applying a micro-scale nuclear magnetic resonance (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c. periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d. evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject.Embodiment 58. A method of evaluating the effectiveness of a treatment for diabetes, obesity, or diabetic kidney disease in a patient undergoing said treatment, said method comprising: a. obtaining a first measurement of an A-ratio of a patient with diabetes, obesity, or diabetic kidney disease to establish a baseline of oxidative stress, wherein an A-ratio comprises a ratio of T1 relaxation time to T2 relaxation time in a micro-scale nuclear magnetic resonance (pNMR) assay; b. obtaining a second measurement of said A-ratio of said patient with diabetes, obesity, or diabetic kidney disease at a later time after said first measurement; and c. determining a percent change between said first measurement and said second measurement.Embodiment 59. The method of embodiment 58, wherein said second measurement of said A-ratio is obtained at least 2 weeks after said first measurement of said A-ratio.Embodiment 60. The method of embodiment 58, wherein said second measurement of said A-ratio is obtained at least 3 weeks after said first measurement of said A-ratio.Embodiment 61 . The method of embodiment 58, wherein said second measurement is obtained at least 4 weeks after said first measurement.Embodiment 62. The method of any one of embodiments 58 to 61. said method comprising maintaining said treatment with respect to dose and administration schedule if said percent change between said first measurement and said second measurement is less than 3% when said second measurement is taken at a time between 14 days and 21 days after said first measurement.Embodiment 63. Hie method of any one of embodiments 58 to 62. said method comprising changing said treatment by increasing a dose of said treatment if said percent change between said first measurement and said second measurement is greater than 3% when said second measurement is taken at least 14 days after said first measurement.Embodiment 64. Hie method of any one of embodiments 58 to 63, said method comprising stopping said treatment if said percent change between said first measurement and said second measurement is greater than 10% when said second measurement is taken at least 2 weeks after said first measurement.Embodiment 65. A method of detecting a metabolic disease marker in a sample, the method comprising detecting a redox state of the sample.Embodiment 66. Hie method according to embodiment 65, wherein the detecting comprises measuring a longitudinal relaxation time (Ti) and a transverse relaxation time (T;) in the sample.Embodiment 67. The method according to embodiment 65 or 66, wherein the detecting is performed by a magnetic resonance relaxometry (MRR).Embodiment 68. Hie method according to any one of embodiment 65 to 67, wherein the method further comprises assessing a redox state of the sample from the longitudinal relaxation time and the transverse relaxation time of the sample.Embodiment 69. The method according to any one of embodiment 65 to 68, wherein assessing the redox state comprises: a. plotting a magnetic state diagram of a longitudinal relaxation time and a transverse relaxation time; and b. interpreting the state of the sample based on a location of the sample in the diagram.Embodiment 70. Hie method according to any one of embodiment 65 to 69, wherein assessing theredox state comprises calculating a ratio of longitudinal relaxation time to transverse relaxation time of the sample (Ratio A).Embodiment 71. The method according to any one of embodiment 65 to 70, further comprising comparing the ratio with a predetermined ratio of a reference sample.Embodiment 72. The method according to any one of embodiments 65 to 71, wherein the metabolic disease marker comprises at least one selected from the group consisting of HbAlc, Albumin Creatinine Ratio (ACR), blood glucose, kidney fibrogenesis (aSMA), body weight, tissue damage, and CD45.Embodiment 73. Hie method according to any one of embodiments 65 to 72, wherein a correlation of Ratio A with the metabolic disease marker is 0.9 or less.Embodiment 74. The method according to any one of embodiments 65 to 73, wherein the metabolic disease marker comprises HbAlc, and a correlation of Ratio A with HbAlc is 0.58 or less.Embodiment 75. Hie method according to any one of embodiments 65 to 75, wherein the metabolic disease marker comprises blood glucose, and a correlation of Ratio A with blood glucose is 0.47 or less.Embodiment 76. The method according to any one of embodiments 65 to 74, wherein the metabolic disease marker comprises ACR, and a correlation of Ratio A with ACR is 0.64 or less.Embodiment 77. Hie method according to any one of embodiments 65 to 76, wherein the metabolic disease marker comprises aSMA, and a correlation of Ratio A with aSMA is 0.23 or less.Embodiment 78. The method according to any one of embodiments 65 to 77, wherein the metabolic disease marker comprises CD45, and a correlation of Ratio A with CD45 is 0.45 or less.Embodiment 79. Hie method according to any one of embodiments 65 to 77, wherein the metabolic disease marker comprises body weight, and a correlation of Ratio A with body weight is 0.8 or less.Embodiment 80. The method according to any one of embodiments 65 to 77, wherein the metabolic disease marker comprises tissue damage, and a correlation of Ratio A with tissue damage is 0.8 or less.Embodiment 81. The method according to any one of embodiments 65 to 78, wherein the sample comprises at least one selected from the group consisting of whole blood, serum, plasma, urine, saliva, sweat, fecal matter, and tears of a subject.Embodiment 82. Tire method according to any one of embodiments 65 to 79, wherein the subject has a metabolic disease.Embodiment 83. The method according to any one of embodiments 65 to 80, wherein the subject has a risk of metabolic disease.Embodiment 84. Hie method according to any one of embodiments 65 to 81, wherein the subject is diagnosed with a metabolic disease.Embodiment 85. The method according to any one of embodiments 65 to 82, wherein the redox state is a level of oxidative stress.Embodiment 86. Hie method according to any one of embodiments 65 to 83, wherein the redox state is a level of oxidative stress of hemoglobin.Embodiment 87. The method according to any one of embodiments 65 to 84, wherein the redox state is a level of nitrosative stress of hemoglobin.Embodiment 88. Hie method according to any one of embodiments 65 to 85, wherein the method further comprises obtaining a sample from a subject.Embodiment 89. The method according to any one of embodiments 65 to 86, wherein the subject has obese.Embodiment 90. Hie method according to any one of embodiments 65 to 86, wherein the subject has obese and further administered drug.Embodiment 91. A method of identifying a risk for a metabolic disease in a subject, the method comprising detecting a redox state of the sample according to the method of any one of the preceding claims.Embodiment 92. A method of monitoring a status of a metabolic disease in a subject in need thereof, the method comprising detecting a metabolic disease marker according to the method of any one of the preceding claims.Embodiment 93. A method of diagnosing a metabolic disease in a sample, the method comprising detecting a metabolic disease marker according to the method of any one of the preceding claims.Embodiment 94. A method of treating a metabolic disease in a subject in need thereof, the method comprising detecting, monitoring a status of, or diagnosing a metabolic disease in the subject according to the method of any one of the preceding claims, and treating the metabolic disease in the subject.Embodiment 95. Tire method of treating according to embodiment 92, wherein the method comprises administering therapeutically effective amount of compound selected from a group comprising a GLP-1 agonist, a biguanide, a meglitinide, an alpha-glucosidase inhibitor, a thiazolidinedione, a DPP -4 inhibitor, a sulfonylurea, a dopamine receptor agonist, a bile acid sequestrant, an SGLT2 inhibitor, a combination medicine, incretin, an incretin derivative, an ACE inhibitor, insulin, an insulin derivative, an amylin analog, and peptide YY.

Claims

CLAIMS1. A method for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said method comprising: a) obtaining a plasma or blood sample from said subject, wherein said subject has been treated with one or more therapies or treatments for said metabolic disorder; b) applying a micro-scale nuclear magnetic resonance (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c) periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d) evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject and determine effectiveness of said one or more therapies or treatments.

2. The method of claim 1, wherein said oxidative stress measurement is calculated as a ratio between a longitudinal proton magnetic resonance relaxation time measurement and a transverse proton magnetic resonance relaxation time measurement of said plasma or blood sample.

3. A method of treating a subject suffering from a metabolic disorder, said method comprising administering to said subject a metabolic disorder therapy, wherein said subject has been determined to be responsive to said metabolic disorder therapy via results from a pNMR assay that measures said subject’s oxidative stress levels from one or more plasma or blood samples of said subject.

4. A system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said system comprising: a) a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; b) a processor; and c) a memory' coupled to said processor and having instructions for said processor to perform any one of the methods of claims 1 to 3.

5. A system for evaluating effectiveness of one or more therapies or treatments for a metabolic disorder on a subject with or at risk of having said metabolic disorder, said system comprising: a) a micro-scalc nuclear magnetic resonance (pNMR) device for conducting pNMR-bascd assays on a plurality of plasma or blood samples; b) a processor; and c) a memory coupled to said processor and having instructions for said processor to: i. determine oxidative stress measurements based on said pNMR-based assays conducted on said plurality of plasma or blood samples, ii. store said determined oxidative stress measurements, and iii. order said determined oxidative stress measurements longitudinally, wherein one or more of disease progression or effectiveness of said one or more therapies or treatments for said metabolic disorder is determined based on said determined oxidative stress measurements that are ordered longitudinally.

6. A method for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having said disorder or disease, said method comprising: a) obtaining a plasma or blood sample from said subject, wherein said subject has been treated with one or more therapies or treatments for said disorder or disease; b) applying a micro-scale magnetic resonance relaxometry (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c) periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d) evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject and determine effectiveness of said one or more therapies or treatments.

7. A method of treating a subject suffering from a disorder or disease, said method comprising administering to said subject a therapy or treatment for said disorder or disease, wherein said subject has been determined to be responsive to said therapy or treatment via results from a micro-scale nuclear magnetic resonance assay that measures said subject’s oxidative stress levels from one or more plasma or blood samples of said subject.

8. A system for evaluating effectiveness of one or more therapies or treatments for a disorder or disease on a subject with or at risk of having said disorder or disease, said system comprising:a) a micro-scale nuclear magnetic resonance (pNMR) device for conducting pNMR-based assays on a plurality of plasma or blood samples; b) a processor; and c) a memory coupled to said processor and having instructions for said processor to: i. determine oxidative stress measurements based on said pNMR-based assays conducted on said plurality of plasma or blood samples, ii. store said determined oxidative stress measurements, and iii. order said determined oxidative stress measurements longitudinally, wherein one or more of disease progression or effectiveness of said one or more therapies or treatments for said disorder or disease arc determined based on said determined oxidative stress measurements that are ordered longitudinally.

9. A method for monitoring disease progression in a subject with or at risk of having a metabolic disorder, said method comprising: a) obtaining a plasma or blood sample from said subject; b) applying a micro-scale nuclear magnetic resonance (pNMR) assay on said plasma or blood sample to generate an oxidative stress measurement of said plasma or blood sample; c) periodically repeating (a) and (b) for a plurality of plasma or blood samples from said subject to generate a plurality of oxidative stress measurements; and d) evaluating said plurality of oxidative stress measurements to monitor disease progression in said subject.

10. A method of evaluating the effectiveness of a treatment for diabetes, obesity, or diabetic kidney disease in a patient undergoing said treatment, said method comprising: a) obtaining a first measurement of an A-ratio of a patient with diabetes, obesity, or diabetic kidney disease to establish a baseline of oxidative stress, wherein an A-ratio comprises a ratio of T1 relaxation time to T2 relaxation time in a micro-scale nuclear magnetic resonance (pNMR) assay; b) obtaining a second measurement of said A-ratio of said patient with diabetes, obesity, or diabetic kidney disease at a later time after said first measurement; and c) determining a percent change between said first measurement and said second measurement.

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