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Description
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
Brown adipose tissue (BAT) is thought to be important in combating obesity as it can expend energy in the form of heat, e.g. thermogenesis. The goal of this study was to study the effect of injected norepinephrine (NE) on the activation of BAT in rats that were fed a high

Brown adipose tissue (BAT) is thought to be important in combating obesity as it can expend energy in the form of heat, e.g. thermogenesis. The goal of this study was to study the effect of injected norepinephrine (NE) on the activation of BAT in rats that were fed a high fat diet (HFD). A dose of 0.25 mg/kg NE was used to elicit a temperature response that was measured using transponders inserted subcutaneously over the BAT and lower back and intraperitoneally to measure the core temperature. The results found that the thermic effect of the BAT increased after the transition from low fat diet to a high fat diet (LFD) yet, after prolonged exposure to the HFD, the effects resembled levels found with the LFD. This suggests that while a HFD may stimulate the effect of BAT, long term exposure may have adverse effects on BAT activity. This may be due to internal factors that will need to be examined further.
ContributorsSion, Paul William (Author) / Herman, Richard (Thesis director) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
According to the CDC, diabetes is the 7th leading cause of death in the U.S. and rates are continuing to rise nationally and internationally. Chronically elevated blood glucose levels can lead to type 2 diabetes and other complications. Medications can be used to treat diabetes, but often have side effects.

According to the CDC, diabetes is the 7th leading cause of death in the U.S. and rates are continuing to rise nationally and internationally. Chronically elevated blood glucose levels can lead to type 2 diabetes and other complications. Medications can be used to treat diabetes, but often have side effects. Lifestyle and diet modifications can be just as effective as medications in helping to improve glycemic control, and prevent diabetes or improve the condition in those who have it. Studies have demonstrated that consuming vinegar with carbohydrates can positively impact postprandial glycemia in diabetic and healthy individuals. Continuous vinegar intake with meals may even reduce fasting blood glucose levels. Since vinegar is a primary ingredient in mustard, the purpose of this study was to determine if mustard consumption with a carbohydrate-rich meal (bagel and fruit juice) had an effect on the postprandial blood glucose levels of subjects. The results showed that mustard improved glycemia by 17% when subjects consumed the meal with mustard as opposed to the control. A wide variety of vinegars exists. The defining ingredient in all vinegars is acetic acid, behind the improvement in glycemic response observed with vinegar ingestion. Vinegar-containing foods range from mustard, to vinaigrette dressings, to pickled foods. The benefits of vinegar ingestion with carbohydrates are dose-dependent, meaning that adding even small amounts to meals can help. Making a conscious effort to incorporate these foods into meals, in addition to an overall healthy lifestyle, could provide an additional tool for diabetics and nondiabetics alike to consume carbohydrates in a healthier manner.
ContributorsJimenez, Gabriela (Author) / Johnston, Carol (Thesis director) / Lespron, Christy (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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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
For the past couple decades, there has been a continuous rise in obesity and Type II Diabetes which has been attributed to the rise in calorically dense diets, especially those heavy in fats. Because of its rising prevalence, accompanied health concerns, and high healthcare costs, detection and therapies for these

For the past couple decades, there has been a continuous rise in obesity and Type II Diabetes which has been attributed to the rise in calorically dense diets, especially those heavy in fats. Because of its rising prevalence, accompanied health concerns, and high healthcare costs, detection and therapies for these metabolic diseases are in high demand. Insulin resistance is a typical hallmark of Type II Diabetes and the metabolic deficiencies in obesity and is the main focus of this project. The primary purpose of this study is (1) detect the presence of two types of insulin resistance (peripheral and hepatic) as a function of age, (2) distinguish if diet impacted the presence of insulin resistance, and (3) determine both the short-term and long-term effects of caloric restriction on metabolic health. The following study longitudinally observed the changes in insulin resistance in high-fat fed and low-fat fed rodents under ad libitum and caloric restriction conditions over the course of 23 weeks. Fasting blood glucose, fasting insulin, body weight, and sensitivity of insulin on tissue were monitored in order to determine peripheral and hepatic insulin resistance. A high fat diet resulted in higher body weights and higher hepatic insulin resistance with no notable effect on peripheral insulin resistance. Caloric restriction was found to alleviate insulin resistance both during caloric restriction and four weeks after caloric restriction ended. Due to sample size, the generalizability of the findings in this study are limited. However, the current study did provide considerable results and can be viewed as a pilot study for a larger-scale study.
ContributorsZuo, Dana (Author) / Trumble, Benjamin (Thesis director) / Herman, Richard (Committee member) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The effects of iron and chromium blood concentrations have been linked to blood glucose control in diabetics. It is suggested that iron causes oxidative stress in the beta cells of the pancreas and adipocytes creating insulin insufficiency and resistance. Chromium is believed to increase the action of insulin

The effects of iron and chromium blood concentrations have been linked to blood glucose control in diabetics. It is suggested that iron causes oxidative stress in the beta cells of the pancreas and adipocytes creating insulin insufficiency and resistance. Chromium is believed to increase the action of insulin through its biologically active molecule chromodulin. Both of these mechanisms are not clear. This 20 week case study tests the feasibility of combining iron depletion therapy followed by chromium supplementation to improve insulin sensitivity. This single case study followed a protocol of two blood donations separated by eight weeks followed by chromium supplementation of 250 µg of chromium picolinate once a day four weeks after the second blood donation. Fasting blood draws were taken at baseline, post blood draws and pre and post chromium supplementation. Results were not promising for the first hypothesis of lowering HbA1c, but the results were promising for the second hypothesis of improving insulin sensitivity by lowering the HOMA score.
ContributorsJarrett, Nia (Author) / Johnston, Carol (Thesis advisor) / Lespron, Christy (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Curcumin is an active ingredient of Curcuma longa (Turmeric) and is studied extensively for its antioxidant, anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer properties. The purpose of this study was to examine the effects of turmeric on blood glucose and plasma insulin levels. The study utilized a placebo-controlled, randomized cross-over

Curcumin is an active ingredient of Curcuma longa (Turmeric) and is studied extensively for its antioxidant, anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer properties. The purpose of this study was to examine the effects of turmeric on blood glucose and plasma insulin levels. The study utilized a placebo-controlled, randomized cross-over design with participants serving as their own control. Eight glucose tolerant healthy participants completed the full study. Three-weeks washout period was kept in between six-weeks. Prior to the test meal day, participants were asked to eat a bagel with their evening dinner. During the day of the test meal, participants reported to the test site in a rested and fasted state. Participants completed mashed potato meal tests with 500 mg of turmeric powder or placebo mixed in water, followed by 3 weeks of 500 mg turmeric or placebo supplement ingestion at home. During this visit blood glucose finger picks were obtained at fasting, 30, 60, 90, and 120 min post-meal. Blood plasma insulin at fasting and at 30 min after the test meal were also obtained. During week 4, participants reported to the test site in a rested and fasted state where fasting blood glucose finger pricks and blood plasma insulin were measured. During week 5 to 7, participants were given a washout time-period. During week 8, entire process from week 1 to 4 was repeated by interchanging the groups. Compared to placebo, reduction in postprandial blood glucose and insulin response were non-significant after ingestion of turmeric powder. Taking turmeric for 3 weeks had no change in blood glucose and insulin levels. However, taking turmeric powder supplements for 3 weeks, showed a 4.4% reduction in blood glucose. Change in insulin at 30 min were compared with baseline insulin level showing no significant change between placebo and turmeric group. Fasting insulin after 3-weeks consumption of turmeric did not show any significant change, but showed a larger effect size (0.08). Future research is essential to examine the turmeric powder supplement benefits over a long period of time in healthy adults and whether it is beneficial in preventing the occurrence of type 2 diabetes.
ContributorsOza, Namrata (Author) / Johnston, Carol (Thesis advisor) / Mayol-Kreiser, Sandra (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2017
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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