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Background Hemodialysis (HD) patients elicit an oxidant-antioxidant imbalance in addition to a selenium deficiency, possibly contributing to cardiovascular disease (CVD) mortality. Objective To evaluate the effect of selenium supplementation on CVD outcomes and antioxidant status in HD patients. Design A randomized controlled intervention trial conducted from October 2012 to January

Background Hemodialysis (HD) patients elicit an oxidant-antioxidant imbalance in addition to a selenium deficiency, possibly contributing to cardiovascular disease (CVD) mortality. Objective To evaluate the effect of selenium supplementation on CVD outcomes and antioxidant status in HD patients. Design A randomized controlled intervention trial conducted from October 2012 to January 2013. Participants/setting The study included 27 maintenance HD patients (61.1+17.5y, 14M, 13F) receiving HD in the greater Phoenix, AZ area. Intervention Patients received one of three treatments daily: 2 Brazil nuts, (5g, 181µg/day of selenium as selenomethionine [predicted]), 1 tablet of selenium (200µg/day of selenium as selenomethionine), or control (3 gummy bears). Main outcome measures Antioxidant status outcome measures included total antioxidant capacity, vitamin C, and RBC and plasma glutathione peroxidase (GSH-Px). CVD outcomes measures included brain natriuretic peptide; plasma cholesterol, high density lipoprotein, low density lipoprotein, triglycerides; blood pressure, and thoracic cavity fluid accumulation. Statistical analyses performed Repeated measures ANOVA analyzed changes over time and between groups at months 0 and 2 and months 0 and 3. Results Independent analysis showed the Brazil nuts provided 11µg of selenium/day and the pill provided 266µg of selenium/day. Consequently, the Brazil nut group was combined with the placebo group. 21 patients completed 2 months of the study and 17 patients completed the study in its entirety. Data was analyzed for months 0, 1 and 2. No significant differences were noted for antioxidant status outcome measures with the exception of plasma GSH-Px. Patients receiving the selenium pill had a significant increase in plasma GSH-Px compared to the placebo group (6.0+11 and -4.0+7.6, respectively, p=0.023 for change between month 0 and month 2). No significant differences were seen in total antioxidant capacity or for CVD outcome measures over time or between groups. Conclusions These data indicate that selenium supplementation increased plasma GSH-Px concentration in HD patients; however, oxidative stress was not altered by selenium supplementation. The low vitamin C status of HD patients warrants further research, specifically in conjunction with selenium supplementation.
ContributorsSussman, Elizabeth Jessica (Author) / Johnston, Carol S (Thesis advisor) / Boren, Kenneth (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Sweazea, Karen (Committee member) / Vaughan, Linda (Committee member) / Arizona State University (Publisher)
Created2013
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The Western Pattern diet has been characterized by having greater than 50 percent consumption coming from fat and sugar. This macronutrient allocation has been shown to have deleterious effects on endothelial function and metabolic markers of cardiovascular disease. Exercise has been shown to improve vascular reactivity and metabolic markers related

The Western Pattern diet has been characterized by having greater than 50 percent consumption coming from fat and sugar. This macronutrient allocation has been shown to have deleterious effects on endothelial function and metabolic markers of cardiovascular disease. Exercise has been shown to improve vascular reactivity and metabolic markers related to cardiovascular health. The objective of the study was to determine if exercise training can prevent the anticipated deleterious effects of a fat-sugar supplemented diet on endothelial function and blood markers of cardiovascular risk in young men. Twenty-one, healthy college-aged males were randomly assigned to either the doughnut + exercise or doughnut only groups. Both groups were fed 2 doughnuts per day, 6 days per week, for three weeks, while maintain their current diet. The exercise group completed 4 exercise training sessions per week consisting of 2 high intensity interval training bouts (up to 95% VO2peak) on a cycle ergometer and two moderate intensity, steady-state bouts (at 75% VO2peak) on a treadmill. Changes in body weight and composition, markers of endothelial function, oxidative stress, serum lipids, and blood glucose were measured in each group. As expected, cardiovascular fitness increased significantly in the doughnut-supplemented + exercise group as compared to the doughnut-supplemented (p=0.005). Significant increases in body weight (p=0.036), fat mass (p=0.013), and body fat percentage (p=0.014) were seen in the doughnut only group as compared to the doughnut + exercise group. The doughnut + exercise group showed significant improvements in fasting serum triglycerides (p=0.036), plasma insulin (p=0.039) and insulin sensitivity (HOMA; p=0.05) as compared to the doughnut only group. The doughnut + exercise group saw a significant improvement in nitric oxide availability whereas the doughnut only group experienced a significant decline (p=0.014). There were no significant changes in other markers. Despite the addition of a fat/sugar supplement of ~11,600 kcal over three weeks, 4 exercise sessions per week were sufficient to prevent a gain in body weight and fat mass, and also improve some measures of cardiometabolic risk. These results suggest that exercise may be necessary to prevent some adverse health outcomes associated with transient periods of excessive energy consumption.
ContributorsBlack, Laurie (Author) / Gaesser, Glenn (Thesis advisor) / Cataldo, Donna (Committee member) / Sweazea, Karen (Committee member) / Vega-Lopez, Sonia (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
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Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a

Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a 2-wk intervention with 2 cups/day of nopales or cucumbers (control), with a 2 to 3-wk washout period. The study included 16 adults (5 male; 46±14 y; BMI = 31.4±5.7 kg/m2) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-c] = 137±21 mg/dL), but otherwise healthy. Main outcomes measured included: dietary intake (energy, macronutrients and micronutrients), cardiometabolic risk markers (total cholesterol, LDL-c, high density lipoprotein cholesterol [HDL-c], triglycerides, cholesterol distribution in LDL and HDL subfractions, glucose, insulin, homeostasis model assessment, and C-reactive protein), and oxidative stress markers (vitamin C, total antioxidant capacity, oxidized LDL, and LDL susceptibility to oxidation). Effects of treatment, time, or interactions were assessed using repeated measures ANOVA. Results: There was no significant treatment-by-time effect for any dietary composition data, lipid profile, cardiometabolic outcomes, or oxidative stress markers. A significant time effect was observed for energy, which was decreased in both treatments (cucumber, -8.3%; nopales, -10.1%; pTime=0.026) mostly due to lower mono and polyunsaturated fatty acids intake (pTime=0.023 and pTime=0.003, respectively). Both treatments significantly increased triglyceride concentrations (cucumber, 14.8%; nopales, 15.2%; pTime=0.020). Despite the lack of significant treatment-by-time effects, great individual response variability was observed for all outcomes. After the cucumber and nopales phases, a decrease in LDL-c was observed in 44% and 63% of the participants respectively. On average LDL-c was decreased by 2.0 mg/dL (-1.4%) after the cucumber phase and 3.9 mg/dL (-2.9%) after the nopales phase (pTime=0.176). Pro-atherogenic changes in HDL subfractions were observed in both interventions over time, by decreasing the proportion of HDL-c in large HDL (cucumber, -5.1%; nopales, -5.9%; pTime=0.021) and increasing the proportion in small HDL (cucumber, 4.1%; nopales, 7.9%; pTime=0.002). Conclusions: These data do not support the purported benefits of nopales at doses of 2 cups/day for 2-wk on markers of lipoprotein profile, cardiometabolic risk, and oxidative stress in hypercholesterolemic adults.
ContributorsPereira Pignotti, Giselle Adriana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Gaesser, Glenn (Committee member) / Keller, Colleen (Committee member) / Shaibi, Gabriel (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2013
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ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia.

ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia. Fifteen male and female subjects were recruited, ages 20-60y, who had no prior history of gastrointestinal (GI) disease or resections impacting normal GI function, were non-smokers, were non-vegetarian/vegan, were not taking any medications known to alter (glucose) metabolism, and were free of chronic disease including diabetes. Subjects were instructed to avoid exercise, alcohol and smoking the day prior to their trials and to consume a standardized, high-carbohydrate dinner meal the eve prior. There was a one-week washout period per subject between appointments. Breath hydrogen, serum insulin and capillary glucose were assessed over 3 hours after a high-starch breakfast meal to evaluate the impact of preprandial supplementation with ACV or placebo (water). Findings confirmed the antiglycemic effects of ACV as documented in previous studies, with significantly lower mean blood glucose concentrations observed during ACV treatment compared to the placebo at 30 min (p=0.003) and 60 min (p=0.005), and significantly higher mean blood glucose concentrations at 180 min (p=0.045) postprandial. No significant differences in insulin concentrations between treatments. No significant differences were found between treatments (p>0.05) for breath hydrogen; however, a trend was observed between the treatments at 180 min postprandial where breath hydrogen concentration was visually perceived as being higher with ACV treatment compared to the placebo. Therefore, this study failed to support the hypothesis that preprandial ACV ingestion produces a higher rate of colonic fermentation within a 3 hour time period following a high-carbohydrate meal. Due to variations in experiment duration noted in other literature, an additional study of similar nature with an expanded specimen collections period, well beyond 3 hours, is warranted.
ContributorsMedved, Emily M (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2012
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Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and its high ability to form AGEs, a further understanding of

Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and its high ability to form AGEs, a further understanding of this association is important to clarify the role of sugars in disease. The objective was to explore the association between usual fructose intake and serum levels of AGEs, as measured by carboxymethyl-lysine (CML) and methylglyoxal derivative (MG-H1), in healthy adults. Methods: This is a secondary analysis of a 15-d controlled feeding study (n=100) with participants consuming their usual diet conducted in the Phoenix metropolitan area. To assess participants’ usual diet, they were asked to complete two 7-d food diaries, which were then used to create custom 15-d menu plans administered during the feeding period. Forty participants were selected based on their 15-d mean total fructose intake for this analysis [top and bottom 20% of the sample distribution (median, IQR); high fructose (HF) n= 20, 72.6 (66.1-90.4) g/day, low fructose (LF) n= 20, 28.8 (22.7-32.2) g/day. Fasting serum collected five weeks after the feeding period were analyzed for CML and MG-H1, two well-established AGEs, using ELISA kits. A database of 549 common foods with known CML amounts was used to calculate exogenous CML intake based on daily food intake data. A general linear model was fitted to investigate the difference in serum CML and MG-H1 between LF and HF groups while adjusting for age, gender, BMI, and exogenous CML intake. Results: Participants in the HF group had significantly higher serum CML and lower MG-H1 levels compared to participants in the LF group (p=0.013 and p=0.002, respectively). This difference remained statistically significant after adjusting for covariates. Conclusions: The findings suggest that endogenous CML formation may be an explanation for the significantly higher serum CML levels in the HF compared to the LF group. This is significant in further understanding mechanisms of fructose intake and disease etiology and could have implications for at-risk populations consuming a high fructose diet.
ContributorsWeigand, Bethany (Author) / Tasevska, Natasha (Thesis advisor) / Sweazea, Karen (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2021
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Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular

Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular vitamin C inadequacy is suspected due to competition between dehydroascorbic acid and glucose at GLUT 1 and 3 cellular receptors. Erythrocyte osmotic fragility is noted in Gulo -/- knockout mice unable to synthesize endogenous vitamin C. The ascorbate deficient red blood cells presented with low cytoskeletal B-spectrin, spherocyte appearance, and impaired deformability. This cross-sectional study investigated the relationships between diabetes status, erythrocyte osmotic fragility, and serum vitamin C status. Participants were aged 18-65, non-smoking, reported no unresolved health complications, and denied prior vitamin C supplementation. Those with T2D indicated diagnosis of >1 year. All participants provided written informed consent and the study was approved by the local Institutional Review Board in January 2021. Participants provided one fasted blood sample. Erythrocyte osmotic fragility was measured via UV/Vis spectrophotometry with various concentrations of sodium chloride (0.85% - 0.10%) to induce osmotic stress. In addition, plasma was extracted and mixed 1:1 with 10% (w/v) metaphosphoric acid in 2 mmol/L disodium EDTA and centrifuged. The supernatant was stored at -80°C until analysis with isocratic reverse-phase UV-HPLC separation. Participant characteristics did not differ significantly between groups apart from age (p< 0.01) and HbA1c (p=0.002). Data are presented for adults with T2D (n=14; 36% female; 55.5±8.2 y; 31.5±9.0 kg/m2; HbA1c: 7.4±1.9%; plasma vitamin C: 36.0±12.2 uM) and without T2D (n=16; 69% female; 38.7±13.5 y; 26.8±6.6 kg/m2; A1c: 5.4±0.3%; plasma vitamin C: 34.8±10.9uM). Erythrocyte osmotic fragility was significantly elevated (+4.4% hemolysis) in adults without T2D at 0.35% saline (p=0.039). Greater VC status (>30 uM) was associated with lower hemolysis at 0.35% NaCl (p=0.031). Erythrocyte osmotic stability was linked to greater vitamin C intake at 0.20% saline in those without T2D (p =0.019). In this pilot study, vitamin C status did not differ significantly by diabetes status. Vitamin C status was directly linked to erythrocyte osmotic stability in adults without T2D.
ContributorsLundy, Ciara Cheyanne (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Alexon, Christy (Committee member) / Arizona State University (Publisher)
Created2022
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Chronic low-grade inflammation is a main pathogenic link between obesity and Type 2 Diabetes (T2D) and a putative target for treatment. While a wide array of pharmacologic agents is available to manage T2D, many patients still face perturbed glycemia and subclinical inflammation. Therefore, complementary nutraceutical strategies that target inflammation, metabolism,

Chronic low-grade inflammation is a main pathogenic link between obesity and Type 2 Diabetes (T2D) and a putative target for treatment. While a wide array of pharmacologic agents is available to manage T2D, many patients still face perturbed glycemia and subclinical inflammation. Therefore, complementary nutraceutical strategies that target inflammation, metabolism, and resolution physiology hold promise as adjunctive options to quell the disturbed immuno-metabolic milieu observed in T2D. Omega-3 polyunsaturated fatty acids (PUFAs) and anthocyanins are two dietary components evidenced to mitigate inflammation and improve T2D risk factors, through distinct and similar targets. However, the combined use of such nutraceuticals has not yet been examined in individuals with T2D. This dissertation leveraged data from a larger randomized, double-blind, placebo-controlled trial conducted between January 2022—September 2023 investigating the use of combined supplementation (active treatment; [FOM]) of anthocyanins (600 mg/d maqui berry extract) and omega-3 PUFAs (3 g/day fish oil; 2 g/d EPA, 1 g/d DHA) for 8 weeks on cytokines and mental acuity in individuals with T2D, compared to a placebo (CON). The current study examined the effects of this supplemental strategy on markers of metabolic inflammation, oxidative stress, and cardiometabolic risk. The results indicated that a marker of sustained omega-3 dietary intake and tissue accumulation termed the Omega-3 Index was inversely associated with HbA1c (? = -8.5, 95%CI -15.1, -1.4, p = 0.022) and glucose (? = -12.4, 95%CI -22.9, -0.5, p = 0.042), after adjustment for covariates at baseline across all participants with T2D in this study. However, outcomes from linear mixed model analyses demonstrated that there were no significant differences in change from baseline between FOM and CON groups at week 8 in any of the inflammatory, oxidative stress, glycemic control, or circulating lipid markers assessed in this study. These null effects were observed despite a 93% greater increase from baseline in the Omega-3 Index observed in the FOM group compared to the CON group at week 8. Therefore, the findings do not support significant treatment effects associated with 2 months of combined marine omega-3 PUFAs and maqui berry extract on inflammatory and cardiometabolic outcomes in individuals with T2D.
ContributorsFessler, Samantha Nicole (Author) / Johnston, Carol S (Thesis advisor) / Sweazea, Karen (Committee member) / Wang, Shu (Committee member) / Kavouras, Stavros A (Committee member) / Grimm, Kevin J (Committee member) / Arizona State University (Publisher)
Created2024
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Fish oil has been extensively researched for its protective effects on cognition. More recently, anthocyanins have also gained the attention of the medical community for their potential cognitive benefits. Maqui berries are one of the richest sources of anthocyanins known to science. While there are many randomized controlled trials (RCT)

Fish oil has been extensively researched for its protective effects on cognition. More recently, anthocyanins have also gained the attention of the medical community for their potential cognitive benefits. Maqui berries are one of the richest sources of anthocyanins known to science. While there are many randomized controlled trials (RCT) investigating the effects of fish oil and/or anthocyanins on cognition in various populations, there are no RCT that exclusively investigate the cognitive effects of these compounds in adults with Type 2 Diabetes (DM2). The purpose of this double-blinded, placebo-controlled RCT was to investigate the cognitive effects of maqui berry extract and fish oil supplements in adults with DM2 over the course of eight weeks. Adults with DM2 (n=29) were recruited by the researchers and randomized to either Group A or Group B. Because the study is ongoing, it is unknown which group received the intervention. The study used the Stroop Test and Trail Making Test (TMT) to measure cognition at baseline, 4 weeks, and 8 weeks. Anthropometrics, blood glucose, and hemoglobin A1C were also taken at these time points. Sixteen female participants were included in the final analysis. Neither group showed significant improvements in the cognitive tests. However, in Group A, the effect sizes were large for the change in Trail-Making Test A (0.167), Trail Making Test B (0.261), and Trail Making Test B minus A (0.296) scores. In Group A, the change in Trail Making Test B minus A scores between baseline and week 4, and between baseline and week 8 was significant (p=0.053) and produced a large effect size (0.258). The results suggest that fish oil and maqui berry extract may improve cognition in adults with DM2, but further studies with larger sample sizes are needed.
ContributorsDeimeke, Allyson (Author) / Johnston, Carol (Thesis advisor) / Grant, Shauna (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2023
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Background: Vegan and vegetarian diets have gained in popularity in recent years. Stated reasons for this include some possible health benefits and concerns of animal welfare. Though considered to be nutritionally adequate, questions remain over whether current protein recommendations of 0.8 g/kg/d are sufficient to maintain body processes and growth.

Background: Vegan and vegetarian diets have gained in popularity in recent years. Stated reasons for this include some possible health benefits and concerns of animal welfare. Though considered to be nutritionally adequate, questions remain over whether current protein recommendations of 0.8 g/kg/d are sufficient to maintain body processes and growth. Protein is unique in that it is the only macronutrient that contains nitrogen. Its status can be determined through nitrogen balance analysis of the urine if protein content of the diet is known. Nitrogen balance is considered the gold standard for determining protein intake requirements. A negative balance indicates a catabolic state, whereas a positive nitrogen balance is seen during anabolism. In healthy people, nitrogen equilibrium is desired under normal circumstances. This equilibrium reflects the net synthesis and breakdown of proteins. While nitrogen balance techniques have been used for decades, currently, there are no known studies measuring nitrogen balance and protein intake in strict vegans. Methods: Twenty vegan, inactive, male participants were recruited and received a 5-day eucaloric diet with a known protein content held constant at 0.8 g/kg/d. On day five, 24-hour urine was collected by participants and aliquoted for future analysis. Nitrogen content of the urine was determined through photometric assay and compared to the known nitrogen content of the diet to calculate nitrogen balance status. Results: Mean absolute nitrogen balance (-1.38 ± 1.22 g/d, effect size = -1.13) was significantly lower than zero (equilibrium) (p < .001). Mean relative nitrogen balance (-18.60 ± 16.96 mg/kg/d, effect size = -1.10) was significantly lower than zero (p < .001). There were no correlations seen between nitrogen balance and age, years as vegan, or fat- free mass. Conclusion: Consuming 0.8 g/kg/d of protein is insufficient to produce nitrogen balance in long-term vegans.
ContributorsBartholomae, Eric (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Wharton, Christopher (Committee member) / Lee, Chong (Committee member) / Kressler, Jochen (Committee member) / Arizona State University (Publisher)
Created2022
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This feasibility study explored the use of an evolutionary mismatch narrative in nutritional education intervention aiming to reduce ultra-processed foods in the diets of veterans with type 2 diabetes and improve diabetic outcomes. Ultra-processed foods are foods that are primarily manufactured through industrial processes. These foods are high in calories

This feasibility study explored the use of an evolutionary mismatch narrative in nutritional education intervention aiming to reduce ultra-processed foods in the diets of veterans with type 2 diabetes and improve diabetic outcomes. Ultra-processed foods are foods that are primarily manufactured through industrial processes. These foods are high in calories but low in nutritional content. Diets high in these foods have been linked to increased health risks. One of the major health risks is type 2 diabetes. Type 2 diabetes is a chronic disease that is developed when cells become unable to properly utilize insulin. Over time this may lead to additional health conditions such as nerve damage, cardiovascular disease, and renal disease. Evolutionary mismatch narrative nutritional intervention offers a different approach to nutritional education to help reduce ultra-processed foods in diets. This study was a randomized controlled feasibility study at the Phoenix VA. Eleven participants were enrolled and randomly selected to be given either an evolutionary mismatch narrative education intervention or general nutritional education about ultra-processed foods. 24-hour diet recalls and blood chemistry were collected and analyzed. Blood chemistry provided diabetes related measurements which included glucose, HbA1c, insulin, HOMA-IR, and C-reactive protein. Statistically significant findings in this study included percentage of ultra-processed foods decreasing for both control and experimental groups from week 0 to week 4 (p=0.014), and C-reactive protein levels between the control and experimental groups (p=0.042). However, baseline C-reactive protein concentrations were lower in the experimental group such that normalizing for group differences at baseline revealed no significant difference in C-reactive protein change between interventions (p = 1.000). There were no other statistically significant values regarding diabetes related measurements. The results from this study suggest that nutritional education in general may help decrease ultra-processed food consumption.

ContributorsLiang, Nathan Adam (Author) / Sweazea, Karen (Thesis advisor) / Basile, Anthony J (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023