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Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that

Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that diets with no meat consumption (pesco-vegetarian and lacto-vegetarian) would reduce protein glycation, in comparison to a diet with meat. Forty six healthy adult omnivorous subjects were randomized into one of three groups and instructed to either consume red meat (i.e. meat) or poultry twice per day (control), eliminate meat and increase fish consumption (pesco-vegetarian), or adopt a vegetarian diet devoid of fish, meat or poultry (lacto-vegetarian) for four weeks. Fasting plasma samples were collected from participants at baseline and after 4 weeks of the dietary intervention. Plasma glucose concentrations were measured using a commercially available kit. Percent glycated albumin was measured on a separate aliquot of plasma by mass spectrometry. Plasma glucose concentrations were significantly increased following 4-weeks of pesco-vegetarian diet (P=0.002, paired t-test). Neither the lacto-vegetarian (P=0.898) or the control diet (P=0.233) affected plasma glucose concentrations. Despite the significant increase in plasma glucose following a pesco-vegetarian diet, no change in percent glycated albumin was observed (P>0.50, ANOVA). These findings may indicate a protective effect of the pesco-vegetarian diet on protein glycation in the presence of elevated plasma glucose and suggest the need for additional studies to examine the link between increased fish consumption and glucose regulation.
ContributorsRaad, Noor (Author) / Sweazea, Karen (Thesis director, Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether

With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether a similar organometallic complex (OMC) could prevent insulin resistance in the skeletal muscle brought on by chronic high fat intake by examining the protein expression of key enzymes in the insulin signaling pathway and examining glucoregulatory measures. Six-week-old periadolescent male Sprague-Dawley rats (n=42) were randomly chosen to be fed either a high fat diet (HFD) (20% protein, 20% carbohydrates [6.8% sucrose], 60% fat) or a standard chow diet (18.9% protein, 57.33% carbohydrates, 5% fat) for 10 weeks. Rats from each diet group were then randomly assigned to one of three doses of OMC (0, 0.6, 3.0 mg/mL), which was added to their drinking water and fasting blood glucose was measured at baseline and again at 10 weeks. After 10 weeks, rats were euthanized, and soleus muscle samples were isolated, snap-frozen, and stored at -80°C until analyses. Fasting plasma glucose was measured using a commercially available glucose oxidase kit. Following 6 and 10 weeks, HFD rats developed significant hyperglycemia (p<0.001 and p=0.025) compared to chow controls which was prevented by high dose OMC (p=0.021). After 10 weeks, there were significant differences in fasting serum insulin between diets (p=0.009) where levels were higher in HFD rats. No significant difference was seen in p-PI3K expression between groups. These results suggest that OMC could prevent insulin resistance by reducing hyperglycemia. Further studies are needed to characterize the effects of diet and OMC on the insulin signaling pathway in skeletal muscle, the main site of postprandial glucose disposal. This study was supported by a grant from Isagenix International LLC as well as funds from Barrett, the Honors College at Arizona State University, Tempe Campus.
ContributorsStarr, Ashlee (Author) / Sweazea, Karen (Thesis director) / Johnston, Carol (Committee member) / Hyatt, JP (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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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
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Description
As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production whereas type 2 diabetes is caused by insulin resistance. Both

As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production whereas type 2 diabetes is caused by insulin resistance. Both types of diabetes lead to increased glucose levels in the body if left untreated. This, in turn, leads to the development of a host of complications, one of which is ischemic heart disease. Accounting for the death of 16% of the world’s population, ischemic heart disease has been the leading cause of death since 2000. As of 2019, deaths from this disease have risen from 2 million to over 8.9 million globally. While medicine exists to counter the negative outcomes of diabetes mellitus, lower income nations suffer from the lack of availability and high costs of these medications. Therefore, this systematic review was performed to determine whether a non-medicinal treatment could provide similar therapeutic benefits for individuals with diabetes. Genistein is a phytoestrogen found in soy-based products, which has been potentially linked with preventing diabetes and improving diabetes-related symptoms such as hyperglycemia and abnormal insulin levels. We searched PubMed and SCOPUS using the terms ‘genistein’, ‘diabetes’, and ‘glucose’ and identified 32 peer-reviewed articles. In general, preclinical studies demonstrate that genistein decreases body weight as well as circulating glucose and triglycerides concentrations while increasing insulin levels and insulin sensitivity. It also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies of genistein in general reported no significant relationship between genistein and body mass, circulating glucose, serum insulin, A1C concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity, delay type 2 diabetes onset and improve serum triglyceride levels. In summary, preclinical and clinical studies suggest that genistein may help delay onset of type 2 diabetes and improve several symptoms associated with the disease. By translating these findings into clinical settings, genistein may offer a cost effective natural approach at mitigating complications associated with diabetes, although additional research is required to confirm these findings.
ContributorsJain, Rijul (Author) / Sweazea, Karen (Thesis director) / Al-Nakkash, Layla (Committee member) / Bolch, Charlotte (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-04-16
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Description
Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative damage allows birds to serve as a negative model of

Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative damage allows birds to serve as a negative model of hyperglycemia-related complications, making them ideal for the development of new diabetes treatments with the potential for human application. Previous studies conducted by the Sweazea Lab at Arizona State University aimed to use diet as a means to raise blood glucose in mourning doves (Zenaida macroura) in order to better understand the mechanisms they utilize to stave off oxidative damage. These protocols used dietary interventions—a 60% high fat (HF) “chow” diet, and a high carbohydrate (HC) white bread diet—but were unsuccessful in inducing pathologies. Based on this research, we hypothesized that a model of an urban diet (high in fat, refined carbohydrates, and sodium) might impair vasodilation, as the effect of this diet on birds is currently unknown. We found that tibial vasodilation was significantly impaired in birds fed an urban diet compared to those fed a seed diet. Unexpectedly, vasodilation in the urban diet group was comparable to data of wild-caught birds from previous research, possibly indicating that the birds had already been eating a diet similar to this study’s urban diet before they were caught. This may constitute evidence that the seed diet improved vasodilation while the urban diet more closely mimicked the diet of the birds before the trial, suggesting that the model of the urban diet acted as the control diet in this context. This study is the first step in elucidating avian mechanisms for dealing with diabetogenic diets and has potential to aid in the development of treatments for humans with metabolic syndrome.
ContributorsRenner, Michael William (Author) / Sweazea, Karen (Thesis director) / Johnston, Carol (Committee member) / Basile, Anthony (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2
diabetes. Experiments including polymerase chain reaction, western blotting, and glycogen

Glucocorticoids are a class of corticosteroids that bind to glucocorticoid receptors
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2
diabetes. Experiments including polymerase chain reaction, western blotting, and glycogen
synthase analysis were conducted to determine if exposure to higher doses of dexamethasone, a
glucocorticoid, induces insulin resistance in cultured rat skeletal muscle via interaction with
thioredoxin-interacting protein (TXNIP). Treatment with dexamethasone was shown to cause
mild increases in TXNIP while a definitive increase or decrease in insulin signaling was unable
to be determined.
ContributorsCusimano, Jason A (Author) / Sweazea, Karen (Thesis director) / Reaven, Peter (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description

Birds naturally have high circulating blood glucose concentrations compared to other vertebrates. Several mechanisms have been proposed to explain their high levels including the lack of an insulin responsive glucose transport protein, higher circulating glucagon concentrations, as well as a reliance on lipid oxidation to fuel the high metabolic demands

Birds naturally have high circulating blood glucose concentrations compared to other vertebrates. Several mechanisms have been proposed to explain their high levels including the lack of an insulin responsive glucose transport protein, higher circulating glucagon concentrations, as well as a reliance on lipid oxidation to fuel the high metabolic demands for flight. We suspected the latter may result in the production of the gluconeogenic precursor, glycerol. Therefore, we examined the hypothesis that gluconeogenesis, via glycerol, contributes to the naturally high glucose concentrations in birds (Madiraju et al., 2014). We captured seven mourning doves, Zenaida macroura, in Tempe, AZ, USA and acclimated the birds to captivity for two weeks. In this crossover design study, doves received either an oral inhibitor of gluconeogenesis (150 or 300 mg/kg metformin) or water (50 ul) each week. We measured blood glucose concentrations using a glucometer at baseline, 30, 60 and 120 minutes following the oral dose. In contrast to mammals and chickens, 300 mg/kg metformin did not alter blood glucose (p>0.05) and 150 mg/kg metformin significantly increased blood glucose concentrations (p=0.043) compared to the oral bolus of water. To examine whether the low dose of metformin stimulated glycogenolysis, thus causing the hyperglycemic effect, we administered the low dose of metformin along with an inhibitor of glycogenolysis, 2.5 mg/kg 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), which prevented the hyperglycemic response (p>0.05 vs. water). These data suggest that low doses of metformin activate glycogenolysis. It is possible that glycogenolysis is also activated at the higher dose, but glycogen may be depleted early on resulting in no measurable changes, given the present study design. In conclusion, and in contrast to the hypothesis, mourning doves may not rely on gluconeogenesis to maintain their naturally high blood glucose concentrations under fed conditions, although further studies with more specific gluconeogenic antagonists and under fasted conditions may be needed to confirm these findings.

ContributorsKreisler, Avin (Author) / Sweazea, Karen (Thesis director) / Basile, Anthony J. (Committee member) / Tucker, Derek (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05