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Monitoring complex diseases and their comorbidities requires accurate and convenient measurements of multiple biomarkers. However, many state-of-the-art bioassays not only require complicated and time-consuming procedures, but also measure only one biomarker at a time. This noncomprehensive single-biomarker monitoring, as well as the cost and complexity of these bioassays advocate for

Monitoring complex diseases and their comorbidities requires accurate and convenient measurements of multiple biomarkers. However, many state-of-the-art bioassays not only require complicated and time-consuming procedures, but also measure only one biomarker at a time. This noncomprehensive single-biomarker monitoring, as well as the cost and complexity of these bioassays advocate for a simple, rapid multi-marker sensing platform suitable for point-of-care or self-monitoring settings. To address this need, diabetes mellitus was selected as the example complex disease, with dry eye disease and cardiovascular disease as the example comorbidities. Seven vital biomarkers from these diseases were selected to investigate the platform technology: lactoferrin (Lfn), immunoglobulin E (IgE), insulin, glucose, lactate, low density lipoprotein (LDL), and high density lipoprotein (HDL). Using electrochemical techniques such as amperometry and electrochemical impedance spectroscopy (EIS), various single- and dual-marker sensing prototypes were studied. First, by focusing on the imaginary impedance of EIS, an analytical algorithm for the determination of optimal frequency and signal deconvolution was first developed. This algorithm helped overcome the challenge of signal overlapping in EIS multi-marker sensors, while providing a means to study the optimal frequency of a biomarker. The algorithm was then applied to develop various single- and dual-marker prototypes by exploring different kinds of molecular recognition elements (MRE) while studying the optimal frequencies of various biomarkers with respect to their biological properties. Throughout the exploration, 5 single-marker biosensors (glucose, lactate, insulin, IgE, and Lfn) and one dual-marker (LDL and HDL) biosensor were successfully developed. With the aid of nanoparticles and the engineering design of experiments, the zeta potential, conductivity, and molecular weight of a biomarker were found to be three example factors that contribute to a biomarker’s optimal frequency. The study platforms used in the study did not achieve dual-enzymatic marker biosensors (glucose and lactate) due to signal contamination from localized accumulation of reduced electron mediators on self-assembled monolayer. However, amperometric biosensors for glucose and lactate with disposable test strips and integrated samplers were successfully developed as a back-up solution to the multi-marker sensing platform. This work has resulted in twelve publications, five patents, and one submitted manuscripts at the time of submission.
ContributorsLin, Chi En (Author) / La Belle, Jeffrey T (Thesis advisor) / Caplan, Michael (Committee member) / Cook, Curtiss B (Committee member) / Stabenfeldt, Sarah (Committee member) / Spano, Mark (Committee member) / Arizona State University (Publisher)
Created2018
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Description

The purpose of this study, which was done in conjunction with the Arizona Heart Foundation, was to evaluate whether pyridoxine accelerates ulcer wound healing in diabetic patients with ulcers in the lower extremities. In this study, 100 mg of pyridoxine per day was given to patients in the experimental grou

The purpose of this study, which was done in conjunction with the Arizona Heart Foundation, was to evaluate whether pyridoxine accelerates ulcer wound healing in diabetic patients with ulcers in the lower extremities. In this study, 100 mg of pyridoxine per day was given to patients in the experimental group (while they receive normal wound treatment) while patients in the control group received normal treatment of wounds without the pyridoxine. Over time, wound healing was evaluated by photographing and then measuring the size of patients' ulcer wounds on the photographs. Results from the experimental group were compared with those of the control group to evaluate the efficacy of the pyridoxine treatment. In addition, comparisons of the healing rates were made with respect to whether the patients smoked, had hypertension or hypotension, and the patients' body mass indexes. It has been found that there was no statistically significant difference in the mean healing rates between the control groups and experimental groups. In addition, it has been found that smoking, BMI and blood pressure did not have a statistically appreciable effect on the difference in mean healing rates between the control and experimental groups. This is evidence that pyridoxine did not have a statistically significant effect on wound healing rates.

ContributorsHaupt, Shawn Anthony (Author) / Caplan, Michael (Thesis director) / Pauken, Christine (Committee member) / Pagan, Pedro (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
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Description
Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials

Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials regarding diabetes in rural Kenya. The resulting documents can easily be adjusted for use in other developing countries.
ContributorsBuchak, Jacqueline (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot

Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot that is unknown about Type II diabetes, and this study will aim to answer some of these questions. The question posed in this study is whether insulin resistance changes as a function of time after the start of a high fat diet. We hypothesized that peripheral insulin resistance would be observed in animals placed on a high fat diet; and peripheral insulin resistance would have a positive correlation with time. In order to test the hypotheses, four Sprague-Dawley male rats were placed on a high fat diet for 8 weeks, during which time they were subjected to three intraperitonal insulin tolerance tests ((NovoLogTM 1 U/kg). These three tests were conducted at baseline (week 1), week 4, and week 8 of the high fat diet. The test consisted of serially determining plasma glucose levels via a pin prick methodology, and exposing a droplet of blood to the test strip of a glucometer (ACCUCHEKTM, Roche Diagnostics). Two plasma glucose baselines were taken, and then every 15 minutes following insulin injection for one hour. Glucose disposal rates were then calculated by simply dividing the glucose levels at each time point by the baseline value, and multiplying by 100. Area under the curve data was calculated via definite integral. The area under the curve data was then subjected to a single analysis of variance (ANOVA), with a statistical significance threshold of p<0.05. The results of the study did not indicate the development of peripheral insulin resistance in the animals placed on a high fat diet. Insulin-mediated glucose disposal was about 50% at 30 minutes in all four animals, during all three testing periods. Furthermore, the ANOVA resulted in p=0.92, meaning that the data was not statistically significant. In conclusion, peripheral insulin resistance was not observed in the animals, meaning no determination could be made on the relation between time and insulin resistance.
ContributorsBrown, Kellen Andrew (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.

ContributorsMishra, Shambhavi (Co-author) / Numani, Asfia (Co-author) / Sweazea, Karen (Thesis director) / Plasencia, Jonathan (Committee member) / Economics Program in CLAS (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers, but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.

ContributorsNumani, Asfia (Co-author) / Mishra, Shambhavi (Co-author) / Sweazea, Karen (Thesis director) / Plasencia, Jon (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

Chronic diseases place a financial burden on the United States and claim the lives of nearly 2 million Americans every year. Among the chronic diseases that plague American people, type 2 diabetes is particularly prevalent and injurious. Thus, action is warranted to improve prevention and management of this disease. Nutrition

Chronic diseases place a financial burden on the United States and claim the lives of nearly 2 million Americans every year. Among the chronic diseases that plague American people, type 2 diabetes is particularly prevalent and injurious. Thus, action is warranted to improve prevention and management of this disease. Nutrition plays a significant role in prevention and management of type 2 diabetes and other chronic diseases. Registered dietitians, as nutrition experts, are qualified to use medical nutrition therapy as a method of prevention and treatment for chronic diseases using a nutritional approach. However, there is no consensus as to which eating pattern is the most efficacious. The aim of this review of research was to examine how plant-based eating patterns impact chronic disease conditions, with an emphasis on type 2 diabetes mellitus, as compared to omnivorous eating patterns. A literature search was conducted through the ASU Library, PubMed, and CINAHL using terms related to plant-based diets and chronic diseases, such as type 2 diabetes. The results revealed that a plant-based eating pattern may be beneficial in the prevention and treatment of certain chronic diseases, such as type 2 diabetes. Specifically, adults who have type 2 diabetes and consume a plant-based diet may exhibit enhanced glycemic control as evidenced by less insulin resistance, increased incretin and insulin secretion, greater insulin sensitivity, and improved HbA1c levels. There is sufficient evidence for registered dietitians to recommend a plant-based approach to patients with type 2 diabetes who would like to achieve enhanced glycemic control.

ContributorsSneddon, Ashley (Author) / Mayol-Kreiser, Sandra (Thesis director) / Shepard, Christina (Committee member) / College of Health Solutions (Contributor, Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Introduction: Diabetes Mellitus (DM) is a significant health problem in the United States, with over 20 million adults diagnosed with the condition. Type 2 Diabetes Mellitus, characterized by insulin resistance, in particular has been associated with various adverse conditions such as chronic kidney disease and peripheral artery disease. The presence

Introduction: Diabetes Mellitus (DM) is a significant health problem in the United States, with over 20 million adults diagnosed with the condition. Type 2 Diabetes Mellitus, characterized by insulin resistance, in particular has been associated with various adverse conditions such as chronic kidney disease and peripheral artery disease. The presence of Type 2 Diabetes in an individual is also associated with various risk factors such as genetic markers and ethnicity. Native Americans, in particular, are more susceptible to Type 2 Diabetes Mellitus, with Native Americans having over two times the likelihood to present with Type 2 DM than non Hispanic whites. Of worry is the Pima Indian population in Arizona, which has the highest prevalence of Type 2 DM in the world. There have been many risk factors associated with the population such as genetic markers and lifestyle changes, but there has not been much research on the utilization of raw data to find the most pertinent factors for diabetes incidence.

Objective: There were three main objectives of the study. One objective was to elucidate potential new relationships via linear regression. Another objective was to determine which factors were indicative of Type 2 DM in the population. Finally, the last objective was to compare the incidence of Type 2 DM in the dataset to trends seen elsewhere.

Methods: The dataset was uploaded from an open source site with citation onto Python. The dataset, created in 1990, was composed of 768 female patients across 9 different attributes (Number of Pregnancies, Plasma Glucose Levels, Systolic Blood Pressure, Triceps Skin Thickness, Insulin Levels, BMI, Diabetes Pedigree Function, Age and Diabetes Presence (0 or 1)). The dataset was then cleaned using mean or median imputation. Post cleaning, linear regression was done to assess the relationships between certain factors in the population and assessed via the probability statistic for significance, with the exclusion of the Diabetes Pedigree Function and Diabetes Presence. Reverse stepwise logistic regression was used to determine the most pertinent factors for Type 2 DM via the Akaike Information Criterion and through the statistical significance in the model. Finally, data from the Center of Disease Control (CDC) Diabetes Surveillance was assessed for relationships with Female DM Percenatge in Pinal County through Obesity or through Physical Inactivity via simple logistic regression for statistical significance.

Results: The majority of the relationships found were statistically significant with each other. The most pertinent factors of Type 2 DM in the dataset were the number of pregnancies, the plasma glucose levels as well as the Blood Pressure. Via the USDS Data from the CDC, the relationships between Female DM Percentage and the obesity and inactivity percentages were statistically significant.

Conclusion: The trends found in the study matched the trends found in the literature. Per the results, recommendations for better diabetes control include more medical education as well as better blood sugar monitoring.With more analysis, there can be more done for checking other factors such as genetic factors and epidemiological analysis. In conclusion, the study accomplished its main objectives.
ContributorsKondury, Kasyap Krishna (Author) / Scotch, Matthew (Thesis director) / Aliste, Marcela (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The aim of this paper is to investigate the B-casein fractions in Scandinavian and Icelandic milk for evidence to either support or refute the claim that the A1 variant of B-casein is diabetogenic in adolescent populations. Based on the theory that differences in milk protein composition explain a lower incidence

The aim of this paper is to investigate the B-casein fractions in Scandinavian and Icelandic milk for evidence to either support or refute the claim that the A1 variant of B-casein is diabetogenic in adolescent populations. Based on the theory that differences in milk protein composition explain a lower incidence of Type 1 Diabetes (T1D) in Iceland when compared to surrounding Nordic countries, an informative poster was created so that a more educated decision can be made by those wishing to take preventative measures against the incidence of the disease. This paper includes a basic background behind the epidemiology of T1D and the Nordic Nutrition Recommendations. Next, comparison between milk protein composition and consumption in Iceland against the other Nordic countries is performed through an in-depth literature review. The review was conducted using PubMed databases until December of 2018. Key findings of this investigation raise concerns regarding the decision between optimizing milk producing rates or breeding for milk devoid of diabetogenic proteins. The current literature on the impact of cattle genetics on the protein composition of milk sheds light on the safety of Icelandic dairy and the resulting health of their population. Icelandic dairy has been evidenced to contain lower levels of A1 b-casein and is considered less diabetogenic. For these reasons, this author would recommend the consumption of Icelandic dairy products over those from other regions.
ContributorsThunberg, Carly Marie (Author) / Morse, Lisa (Thesis director) / Grgich, Traci (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Type 2 diabetes mellitus (T2DM) is a life-long disease that affects over 27 million individuals in the United States alone. There are many different risk factors and pre-indicators of T2DM. One of them is insulin resistance. Insulin resistance occurs when the body is unable to appropriately respond to insulin. This

Type 2 diabetes mellitus (T2DM) is a life-long disease that affects over 27 million individuals in the United States alone. There are many different risk factors and pre-indicators of T2DM. One of them is insulin resistance. Insulin resistance occurs when the body is unable to appropriately respond to insulin. This in turn leads to increased levels of glucose and insulin in the bloodstream. Unlike T2DM, insulin resistance is a reversible diagnosis. The purpose of this project was to identify the most influential genetic and dietary factors of insulin resistance and to see if individuals have some extent of control to possibly avoid the diagnosis of insulin resistance and possibly T2DM entirely.
A total of 26 human subjects were used in this study. Each subject was classified as either lean or obese, according to their BMI measurement. First, the subjects underwent an oral glucose tolerance test. Blood samples were taken to measure glucose levels in the blood. After the test subject characteristics for each subject was obtained. These included age, BMI, body fat percentage, fat free mass (FFM), height, total mass, waist circumference, hip circumference, and waist to hip ratio. After the subject characteristics and blood glucose were measured the blood samples taken previously were then centrifuged, and the blood plasma was extracted. The blood plasma was then used to undergo an Insulin ELISA test. After extensive analysis, the Matsuda Index of each subject was obtained. Subjects with a Matsuda value of 6.0 or under were considered insulin resistant while subjects with a Matsuda value higher than 6.0 were considered insulin sensitive. Subjects were also required to submit a dietary record over the course of three days. The food intake was then put into a food processing software which gave a daily average of the macro and micro nutrients for each subject. Both the subject and dietary values were put into a multiple regression with a significance factor of p < 0.5 to see which factors contributed most to the Matsuda value.
It was found that BMI, height, total mass, insulin and fat free mass, all of which were subject characteristics, were considered to be significant. Some of these factors an individual has no control over, such as height and insulin. However other factors such as BMI, total mass and fat free mass can be affected by both a healthy diet and frequent exercise. This study validated that diet and physical activity can greatly influence an individual’s susceptibility to insulin resistance and ultimately T2DM.
ContributorsBrinkerhoff, Catalina Marie (Author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05