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- All Subjects: Diabetes
Diabetes affects millions of people globally and can lead to other severe health complications when undiagnosed or not properly managed. The incidence of diabetes has rapidly increased over the past several years, however, not all individuals have access to affordable or convenient healthcare. We hypothesize that wastewater-based epidemiology (WBE) has the potential to assess community health status by analyzing biomarkers indicative of human health and disease, including diabetes. Used in tandem with current methods, monitoring indicators of diabetes in community wastewater could provide a comprehensive assessment tool for disease prevalence in large and small populations. Specifically, the proposed targeted biomarker evaluated in this study to indicate population-wide diabetes prevalence was 8-hydroxy-2’- deoxyguanosine (8-OHdG). This work combines a rigorous literature review and initial laboratory studies to explore the possibility of diabetes monitoring at the community level using WBE. Here, 24-hour composite wastewater samples were collected from within two wastewater sub-catchments of Greater Tempe, AZ. Overall goals of this study were to: i) Determine the feasibility to detect endogenous markers of diabetes in community wastewater; ii) Assess the potential impact of confounding factors, such as smoking, cancer, and atherosclerosis, through a literature analysis; and iii) Evaluate the socioeconomic status and demographics of the study population. Preliminary results of the experiments suggest this methodology to be feasible, as indicated by the observation of detectable signals of 8-OHdG in community wastewater collected from the sewer infrastructure; however, future work and continued experimentation will be required to address low signal intensity and assay precision and accuracy. Thus, the work presented here provides valuable proof-of-concept data, with detailed information on the method employed and identified opportunities to further determine the relationship between 8-OHdG concentrations in municipal wastewater and diabetes prevalence at the community level.
Diabetes affects millions of people globally and can lead to other severe health complications when undiagnosed or not properly managed. The incidence of diabetes has rapidly increased over the past several years, however, not all individuals have access to affordable or convenient healthcare. We hypothesize that wastewater-based epidemiology (WBE) has the potential to assess community health status by analyzing biomarkers indicative of human health and disease, including diabetes. Used in tandem with current methods, monitoring indicators of diabetes in community wastewater could provide a comprehensive assessment tool for disease prevalence in large and small populations. Specifically, the proposed targeted biomarker evaluated in this study to indicate population-wide diabetes prevalence was 8-hydroxy-2’-deoxyguanosine (8-OHdG). This work combines a rigorous literature review and initial laboratory studies to explore the possibility of diabetes monitoring at the community level using WBE. Here, 24-hour composite wastewater samples were collected from within two wastewater sub-catchments of Greater Tempe, AZ. Overall goals of this study were to: i) Determine the feasibility to detect endogenous markers of diabetes in community wastewater; ii) Assess the potential impact of confounding factors, such as smoking, cancer, and atherosclerosis, through a literature analysis; and iii) Evaluate the socioeconomic status and demographics of the study population. Preliminary results of the experiments suggest this methodology to be feasible, as indicated by the observation of detectable signals of 8-OHdG in community wastewater collected from the sewer infrastructure; however, future work and continued experimentation will be required to address low signal intensity and assay precision and accuracy. Thus, the work presented here provides valuable proof-of-concept data, with detailed information on the method employed and identified opportunities to further determine the relationship between 8-OHdG concentrations in municipal wastewater and diabetes prevalence at the community level.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.