Matching Items (12)
Description
Metabolomics focuses on the study of metabolic changes occurring in varioussystems and utilizes quantitative and semi-quantitative measurements of multiple metabolites in parallel. Mass spectrometry (MS) is the most ubiquitous platform in this field, as it provides superior sensitivity regarding measurements of complex metabolic profiles in biological systems. When combined with MS, multivariate statistics and advanced machine learning algorithms provide myriad opportunities for bioinformatics insights beyond simple univariate data comparisons. In this dissertation, the application of MS-based metabolomics is introduced with an emphasis on biomarker discovery for human disease detection. To advance disease diagnosis using MS-based metabolomics, numerous statistical techniques have been implemented in this research including principal component analysis, factor analysis, partial least squares-discriminant analysis (PLS-DA), orthogonal PLS-DA, random forest, receiver operating characteristic analysis, as well as functional pathway/enzyme enrichment analyses. These approaches are highly useful for improving classification sensitivity and specificity related to disease-induced biological variation and can help identify useful biomarkers and potential therapeutic targets. It is also shown that MS-based metabolomics can distinguish between clinical and prodromal disease as well as similar diseases with related symptoms, which may assist in clinical staging and differential diagnosis, respectively. Additionally, MS-based metabolomics is shown to be promising for the early and accurate detection of diseases, thereby improving patient outcomes, and advancing clinical care. Herein, the application of MS methods and chemometric statistics to the diagnosis of breast cancer, coccidioidomycosis (Valley fever), and senile dementia (Alzheimer's disease) are presented and discussed. In addition to presenting original research, previous efforts in biomarker discovery will be synthesized and appraised. A Comment will be offered regarding the state of the science, specifically addressing the inefficient model of repetitive biomarker discovery and the need for increased translational efforts necessary to consolidate metabolomics findings and formalize purported metabolic markers as laboratory developed tests. Various factors impeding the translational throughput of metabolomics findings will be carefully considered with respect to study design, statistical analysis, and regulation of biomedical diagnostics. Importantly, this dissertation will offer critical insights to advance metabolomics from a scientific field to a practical one including targeted detection, enhanced quantitation, and direct-to-consumer considerations.
ContributorsJasbi, Paniz (Author) / Johnston, Carol S (Thesis advisor) / Gu, Haiwei (Thesis advisor) / Lake, Douglas F (Committee member) / Sweazea, Karen (Committee member) / Tasevska, Natasha (Committee member) / Arizona State University (Publisher)
Created2022
Description
Background: Postprandial hyperglycemia can increase levels of oxidative stress and is an independent risk factor for complications associated with type 2 diabetes.
Purpose: To evaluate the acute effects of a 15-min postmeal walk on glucose control and markers of oxidative stress following a high-carbohydrate meal.
Methods: Ten obese subjects (55.0 ± 10.0 yrs) with impaired fasting glucose (107.1 ± 9.0 mg/dL) participated in this repeated measures trial. Subjects arrived at the laboratory following an overnight fast and underwent one of three conditions: 1) Test meal with no walking or fiber (CON), 2) Test meal with 10g fiber and no walking (FIB), 3) Test meal with no fiber followed by a 15-min treadmill walk at preferred walking speed (WALK). Blood samples were taken over four hours and assayed for glucose, insulin, thiobarbituric reactive substances (TBARS), catalase, uric acid, and total antioxidant capacity (TAC). A repeated measures ANOVA was used to compare mean differences for all outcome variables.
Results: The 2hr and 4hr incremental area under the curve (iAUC) for glucose was lower in both FIB (2hr: -93.59 mmol∙120 min∙L-1, p = 0.006; 4hr: -92.59 mmol∙240 min∙L-1; p = 0.041) and WALK (2hr: -77.21 mmol∙120 min∙L-1, p = 0.002; 4hr: -102.94 mmol∙240 min∙L-1; p = 0.005) conditions respectively, compared with CON. There were no differences in 2hr or 4hr iAUC for glucose between FIB and WALK (2hr: p = 0.493; 4hr: p = 0.783). The 2hr iAUC for insulin was significantly lower in both FIB (-37.15 μU ∙h/mL; p = 0.021) and WALK (-66.35 μU ∙h/mL; p < 0.001) conditions, compared with CON, and was significantly lower in the WALK (-29.2 μU ∙h/mL; p = 0.049) condition, compared with FIB. The 4hr iAUC for insulin in the WALK condition was significantly lower than both CON (-104.51 μU ∙h/mL; p = 0.001) and FIB (-77.12 μU ∙h/mL; p = 0.006) conditions. Markers of oxidative stress were not significantly different between conditions.
Conclusion: A moderate 15-minute postmeal walk is an effective strategy to reduce postprandial hyperglycemia. However, it is unclear if this attenuation could lead to improvements in postprandial oxidative stress.
Purpose: To evaluate the acute effects of a 15-min postmeal walk on glucose control and markers of oxidative stress following a high-carbohydrate meal.
Methods: Ten obese subjects (55.0 ± 10.0 yrs) with impaired fasting glucose (107.1 ± 9.0 mg/dL) participated in this repeated measures trial. Subjects arrived at the laboratory following an overnight fast and underwent one of three conditions: 1) Test meal with no walking or fiber (CON), 2) Test meal with 10g fiber and no walking (FIB), 3) Test meal with no fiber followed by a 15-min treadmill walk at preferred walking speed (WALK). Blood samples were taken over four hours and assayed for glucose, insulin, thiobarbituric reactive substances (TBARS), catalase, uric acid, and total antioxidant capacity (TAC). A repeated measures ANOVA was used to compare mean differences for all outcome variables.
Results: The 2hr and 4hr incremental area under the curve (iAUC) for glucose was lower in both FIB (2hr: -93.59 mmol∙120 min∙L-1, p = 0.006; 4hr: -92.59 mmol∙240 min∙L-1; p = 0.041) and WALK (2hr: -77.21 mmol∙120 min∙L-1, p = 0.002; 4hr: -102.94 mmol∙240 min∙L-1; p = 0.005) conditions respectively, compared with CON. There were no differences in 2hr or 4hr iAUC for glucose between FIB and WALK (2hr: p = 0.493; 4hr: p = 0.783). The 2hr iAUC for insulin was significantly lower in both FIB (-37.15 μU ∙h/mL; p = 0.021) and WALK (-66.35 μU ∙h/mL; p < 0.001) conditions, compared with CON, and was significantly lower in the WALK (-29.2 μU ∙h/mL; p = 0.049) condition, compared with FIB. The 4hr iAUC for insulin in the WALK condition was significantly lower than both CON (-104.51 μU ∙h/mL; p = 0.001) and FIB (-77.12 μU ∙h/mL; p = 0.006) conditions. Markers of oxidative stress were not significantly different between conditions.
Conclusion: A moderate 15-minute postmeal walk is an effective strategy to reduce postprandial hyperglycemia. However, it is unclear if this attenuation could lead to improvements in postprandial oxidative stress.
ContributorsKnurick, Jessica (Author) / Johnston, Carol S (Thesis advisor) / Sweazea, Karen L (Committee member) / Gaesser, Glenn A (Committee member) / Shaibi, Gabriel Q (Committee member) / Lee, Chong D (Committee member) / Arizona State University (Publisher)
Created2015