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- Creators: Arizona State University
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Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Objective: Vinegar consumption studies have demonstrated possible therapeutic effects in reducing HbA1c and postprandial glycemia. The purpose of the study was to closely examine the effects of a commercial vinegar drink on daily fluctuations in fasting glucose concentrations and postprandial glycemia, and on HbA1c, in individuals at risk for Type 2 Diabetes Mellitus (T2D). Design: Thirteen women and one man (21-62 y; mean, 46.0±3.9 y) participated in this 12-week parallel-arm trial. Participants were recruited from a campus community and were healthy and not diabetic by self-report. Participants were not prescribed oral hypoglycemic medications or insulin; other medications were allowed if use was stable for > 3 months. Subjects were randomized to one of two groups: VIN (8 ounces vinegar drink providing 1.5 g acetic acid) or CON (1 vinegar pill providing 0.04 g acetic acid). Treatments were taken twice daily immediately prior to the lunch and dinner meals. Venous blood samples were drawn at trial weeks 0 and 12 to measure insulin, fasting glucose, and HbA1c. Subjects recorded fasting glucose and 2-h postprandial glycemia concentrations daily using a glucometer. Results: The VIN group showed significant reductions in fasting capillary blood glucose concentrations (p=0.05) that were immediate and sustained throughout the duration of the study. The VIN group had reductions in 2-h postprandial glucose (mean change of −7.6±6.8 mg/dL over the 12-week trial), but this value was not significantly different than that for the CON group (mean change of 3.3±5.3 mg/dL over the 12-week trial, p=0.232). HbA1c did not significantly change (p=0.702), but the reduction in HbA1c in the VIN group, −0.14±0.1%, may have physiological relevance. Conclusions: Significant reductions in HbA1c were not observed after daily consumption of a vinegar drink containing 1.5 g acetic acid in non-diabetic individuals. However, the vinegar drink did significantly reduce fasting capillary blood glucose concentrations in these individuals as compared to a vinegar pill containing 0.04 g acetic acid. These results support a therapeutic effect for vinegar in T2D prevention and progression, specifically in high-risk populations.
ContributorsQuagliano, Samantha (Author) / Johnston, Carol (Thesis advisor) / Appel, Christy (Committee member) / Dixon, Kathleen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Type 2 diabetes affects approximately 7.3% of Americans, leading to debilitating and life-threatening comorbidities. Estrogen and testosterone levels have been linked to inflammatory and oxidative stress markers, as well as glucose and insulin concentrations. The present study was designed to determine the link between sex differences, glucose control, and inflammation and oxidative stress related to daily almond ingestion among subjects with type 2 diabetes. Subjects were randomized to an intervention group, which received 1.5 oz. almonds daily for 12 weeks, or to the matched control group, which maintained their current diet. No significant differences were found in changes in glucose control in response to ingestion of almonds. However, CRP was significantly reduced by an average of 36.2% in those that received almonds daily (p = 0.017). Although not significant, women randomized to the intervention group appeared to have improvements in insulin resistance compared to women with no dietary change. Results suggest that the addition of almonds to the diet may be an effective intervention for managing inflammation associated with type 2 diabetes. The addition of almonds to the diet is a low cost intervention that is easily implemented into daily lifestyle. Due to the small sample size, additional studies are needed to determine the impact and mechanisms of almond ingestion in subjects with type 2 diabetes.
ContributorsPetersen, Katherine Nicole (Author) / Karen, Sweazea (Thesis advisor) / Carol, Johnston (Committee member) / Christy, Lespron (Committee member) / Arizona State University (Publisher)
Created2014
Description
The omega-3 fatty acids in fatty fish and fish oil, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), have been associated with a reduction in risk for cardiovascular disease. Blood type is a known contributor to risk for cardiovascular events. This study evaluated the effect of fish oil supplements on cardiovascular risk markers in adults with blood types A or O. An 8-week parallel-arm, randomized, double-blind trial was conducted in healthy adult men and women with either blood type A (BTA) or blood type O (BTO). Participants were randomized to receive fish oil supplements (n=10 [3 BTA/7 BTO]; 2 g [containing 1.2 g EPA+DHA]/d) or a coconut oil supplement (n=7 [3 BTA/4 BTO]; 2 g/d). Markers that were examined included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), and hemoglobin A1C (HbA1C). Results indicated that the percent change in LDL cholesterol was significantly greater in the coconut oil group vs the fish oil group (-14.8±12.2% vs +2.8±18.9% respectively, p=0.048). There were no other significant differences between treatment groups, or between blood types A and O, for the other cardiovascular risk markers. Further research with a larger and more diverse sample may yield a more conclusive result.
ContributorsHerring, Dana (Author) / Johnston, Carol (Thesis advisor) / Vega-Lopez, Sonia (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2014
Description
Nationally, African Americans suffer disproportionately from diabetes; with 13.2% of African Americans diagnosed with diabetes compared to 7.6% of non-Hispanic whites (CDC, 2014). Nearly one-half of all people with diabetes are non-adherent to their oral medications; adherence to insulin therapy was 60%-80% (Brunton et al., 2011; Cramer, 2004; Rubin, 2005). This study explored the question, "What mechanisms are associated with adherence to diabetes medication, including insulin, for African Americans in the Southwest?" Twenty-three people participated in the study; 17 participated in interviews and six participated in gendered focus groups. A community-based participatory research (CBPR) approach engaged the African American community as partners in research.
Major themes emerging from the data included illness perception, support, and the process of medication adherence. Acceptance of the diabetes diagnosis was imperative for medication adherence. Stigmatization of diabetes was salient in the recruitment process and as it related to mechanisms for adherence. Furthermore, many informants were not aware of a family history of diabetes before their own diagnosis. Four gendered emerging typologies were identified, which further illuminated major themes. Moreover, an eight-step process of medication adherence model is discussed. The researcher was able to identify culturally compatible strategies that may be extended to those struggling with medication adherence. The implications section suggests a set of strategies that healthcare providers can present to people with diabetes in order to increase medication adherence.
Major themes emerging from the data included illness perception, support, and the process of medication adherence. Acceptance of the diabetes diagnosis was imperative for medication adherence. Stigmatization of diabetes was salient in the recruitment process and as it related to mechanisms for adherence. Furthermore, many informants were not aware of a family history of diabetes before their own diagnosis. Four gendered emerging typologies were identified, which further illuminated major themes. Moreover, an eight-step process of medication adherence model is discussed. The researcher was able to identify culturally compatible strategies that may be extended to those struggling with medication adherence. The implications section suggests a set of strategies that healthcare providers can present to people with diabetes in order to increase medication adherence.
ContributorsWardian, Jana (Author) / Marsiglia, Flavio F (Thesis advisor) / Sun, Fei (Committee member) / Shaibi, Gabriel (Committee member) / Arizona State University (Publisher)
Created2015
Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Mexican Americans have an increased risk for type 2 diabetes and premature cardiovascular disease (CVD). The association of hyperglycemia with traditional CVD risk factors in this population has been established, but there is limited data regarding other non-traditional CVD risk factors. Thus, this cross-sectional study was conducted to evaluate CVD risk among Mexican Americans by measuring concentrations of lipids, high-sensitivity C-reactive protein (hsCRP), and cholesterol in low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfractions. Eighty overweight/obese Mexican-American adults participating in the Maricopa Insulin Resistance Initiative were randomly selected from each of the following four groups (n = 20 per group): nomolipidemic
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ContributorsNeupane, Srijana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Shaibi, Gabriel Q (Committee member) / Johnston, Carol S (Committee member) / Arizona State University (Publisher)
Created2011
Description
Many people with or at risk for diabetes have difficulty maintaining normal postprandial blood glucose levels (120-140 mg/dl). Research has shown that vinegar decreases postprandial glycemia. The purpose of this study was to examine a possible mechanism by which vinegar decreases postprandial glycemia, particularly the effect of vinegar ingestion on gut fermentation. In this parallel arm randomized control trial, the effects of daily ingestion of vinegar on gut fermentation markers were observed among adults at risk for type 2 diabetes in Phoenix, Arizona. Subjects (n=14) were randomly assigned to treatments consisting of a vinegar drink (1.5g acetic acid) or a placebo (2 vinegar pills containing 40mg acetic acid each). All participants were required to consume the vinegar drink (16 oz) or 2 placebo pills every day for 12 weeks. At week 12, participants filled out a questionnaire to report gastrointestinal (GI) symptoms and three consecutive breath samples were taken from each subject to measure fasting breath hydrogen (BH2) with a breath analyzer. Fasting BH2 measures for the vinegar drink group (16.1+11.8 ppm) were significantly different than those from the pill group (3.6+1.4) with a partial eta squared of 0.39 (p=0.023). After adjusting for age as a confounding factor (r=0.406) and removing an outlier, fasting BH2 measures for the vinegar drink group (4.3+1.1 ppm) were still significantly different than those from the pill group (3.6+1.4) with a partial eta squared of 0.35 (p=0.045). Participants in both groups reported mild changes in GI symptoms. In conclusion, adults at risk for type 2 diabetes that consume 2 tablespoons of vinegar a day may have increased gut fermentation compared to those who do not consume vinegar.
ContributorsWhite, Serena (Author) / Johnston, Carol (Thesis advisor) / Appel, Christy (Committee member) / Martin, Keith (Committee member) / Arizona State University (Publisher)
Created2013
Description
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