Browsing by Subject "diabetes"

Now showing 1 - 13 of 13
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    Design of an Oxygen-Delivering Porous Chitosan Scaffold Encapsulated in a Calcium Alginate Hydrogel for Treatment of Hypoxic Wounds
    (2018-07) Kollaja, Benjamin
    Several oxygen-delivering wound dressings have been proposed in recent literature with the aim of improving healing outcomes of chronic wounds. Oxygen generation has been achieved in numerous ways, including the incorporation of peroxide salts and perfluorocarbons (PFCs) to provide oxygen-loading capacity. Here, we have designed a multilayer wound dressing composed of chitosan encapsulated in calcium alginate, incorporating calcium peroxide and PFCs to act as oxygen-generators and oxygen shuttles, respectively. We hypothesize that the combination of oxygen-generating CaO2 and oxygen-carrying PFCs will act synergistically to improve sustained oxygen delivery to the underlying wound and thus improve healing outcomes. Oxygen generation is quantified by fluorescence microscopy using aqueous tris(bipyridine)ruthenium (II) chloride in a closed flow system.
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    Diabetes During Pregnancy: a guide for mothers-to-be diagnosed with Gestational Diabetes
    (2011-12-01) Morcomb, Erin
    Gestational Diabetes occurs in pregnant women who have never been diagnosed with diabetes before but who have high blood sugar (glucose) levels during pregnancy. The exact cause is unknown. Some scientists believe that it is caused by hormones released from the placenta, the structure that helps support the baby as it grows inside of its mother. These hormones are important for the baby’s development, but they can also lead to a phenomenon called insulin resistance, which makes it hard for the mother’s body to use insulin even though it is making enough of it. Since insulin is responsible for getting glucose into cells so that it can be used for energy, and since the mother’s body is resistant to it, the sugar builds up in the blood. This is called hyperglycemia, and it can lead to devastating consequences for both the mom and baby.
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    Diabetes Management After Failed Glycemic Control on Metformin
    (2009-09-18) Huseby, Krysta
    Many patients with type 2 diabetes are initially treated with metformin, but after a while, metformin alone may not be enough to control their blood sugars. This is a patient guide describing different medications a patient might add on to metformin to get better control.
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    Discrimination and Depressive Symptom Trajectories of Middle-aged and Older Adults with Chronic Diseases
    (2021-07) Yoon, Young Ji
    Depression is a serious health concern for adults who have been diagnosed with cancer or diabetes. In addition to the challenges associated with chronic disease management, perceived discrimination has been identified as a factor that increases the risk of depressive symptoms. However, empirical evidence using longitudinal data to test the association between perceived discrimination and depressive symptoms of those with cancer or diabetes is limited. Using Andersen’s Behavioral Model and the Theory of Fundamental Causes as guiding frameworks, this three-paper dissertation study presents a scoping review (Study 1) and two quantitative studies (Studies 2 and 3) to investigate the association between perceived discrimination and depressive symptoms among middle-aged and older adults with a cancer history or diabetes. In Study 1, an assessment of 23 peer-reviewed journal articles provides strong empirical evidence for statistically significant direct or indirect relationships between discrimination/stigma and depressive symptoms. In Studies 2 and 3, latent growth modeling using data from the Health and Retirement Study indicates that cancer survivors had an increasing linear trajectory of depressive symptoms and people with diabetes had a decreasing linear trajectory of depressive symptoms over a 4-year period (Study 2: 2010–2014, Study 3: 2014-2018). Findings from these studies support the need for social workers and other members of the health care team to offer tailored assessment and treatment approaches to address depressive symptoms for cancer survivors and people with diabetes, especially those who may perceive discrimination based on their race, ethnicity, socioeconomic status, culture, language, and having a medical diagnosis. Implications for future investigations are discussed.
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    The effects of yeast beta-glucan on diabetes, liver cholesterol and fatty liver in rodents.
    (2016-08) Feng, Fanqing
    This dissertation’s main focus is on how yeast beta-glucans affect: (1) the glycemic control of diabetes (fasting blood glucose, proportion of glycated hemoglobin and postprandial glycemic response) and (2) hepatic lipid accumulation and hepatic cholesterol concentration in chemically-induced diabetic rats. Further, in order to understand which characteristic of yeast beta-glucans might be responsible for the effects found, small intestinal contents viscosity was measured after a meal containing yeast beta-glucans and fermentation with the yeast beta-glucans. The results of this study indicates that yeast beta-glucans have no viscosity but some fermentability, does not improve glycemic control in diabetes but does reduce hepatic cholesterol. Thus, this dissertation implies that viscosity is likely the important characteristic of beta-glucans responsible for improving hyperglycemia in diabetes rather than fermentability.
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    Life Course Evaluation of a Plant-Centered Diet and Risk of Type 2 Diabetes, Weight Gain, Cardiovascular Diseases, All-Cause Mortality, and Markers of Chronic Kidney Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Cohort
    (2021-01) Choi, Yuni
    OBJECTIVE: To examine the association of plant-centered diet quality with risk of type 2 diabetes (T2D), weight gain, cardiovascular disease (CVD), all-cause mortality, and markers of chronic kidney disease (CKD)−estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR).METHODS: Data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort were used. This US multicenter, community-based prospective study involved 5,115 Black and White men and women aged 18-30 years old at baseline assessment in 1985–1986 and followed through to 2018. Diet was assessed by an interviewer-administered, validated diet history questionnaire. Plant-centered diet quality was assessed using the A Priori Diet Quality Score (APDQS); higher index scores represent higher consumption of nutritionally-rich plant foods and limited consumption of high-fat meat products and unhealthy plant foods. Cox regression models were used to assess risk of T2D, CVD, and all-cause mortality, and linear regression models were used to examine change in body size, eGFR, ACR, and combination of eGFR and ACR. RESULTS: For every 1–SD increase in the APDQS (over a 20-year period for T2D and a 13-year period for CVD), there was a reduction in subsequent risk of T2D (Hazard Ratio [HR]= 0.71; 95% CI: 0.59–0.86) and CVD (HR=0.75; 95% CI: 0.57–1.00), independent of the baseline APDQS. In addition, each 1–SD increase in the APDQS over 20 years was associated with concurrent changes in body mass index (-0.39±0.14 kg/m2; P=0.004), waist circumference (-0.90±0.27 cm; P <0.001), and body weight (-1.14±0.33 kg; P <0.001). The time-updated average APDQS was associated with lower risk of CVD (HR=0.80; 95% CI: 0.67–0.95), lower ln(ACR) (β±SE at Y30: -0.09±0.02 mg/g; P<0.001), higher eGFR (1.64±0.47 mL/min/1.73m2; P<0.001), and lower the combined markers (for ln(ACR) z-score - eGFR z-score: -0.19±0.03; P<0.001). However, there was a suggestive, but not statistically significant, inverse association between the APDQS and risk of all-cause mortality. CONCLUSIONS: Consumption of a plant-centered, high-quality diet starting in young adulthood is associated with a lower risk of developing diet-related chronic disease by middle age.
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    Monitoring and improving oxygenation of organs, cells, and tissue engineered grafts
    (2015-12) Weegman, Bradley
    Oxygen is vital to the survival of many living things, and evolution has provided the human body with a complex cardiovascular system to ensure that all of the cells in the body are provided with adequate oxygen. Achieving adequate oxygen delivery remains of critical importance to the clinical management of many human diseases and has been the impetus for the development of many medical procedures and technologies. Despite much advancement in the understanding about oxygen delivery in the body, the current inability to attain life-sustaining levels of tissue oxygenation remains the major limitation for the emerging fields of cell, tissue, and organ replacement. There is a large body of research focused on developing methods to improve vascularization and oxygen supply for transplanted cells, tissues and organs, and this substantial challenge will require an interdisciplinary approach utilizing both engineering principles and a broad understanding of the physical science. The islet transplantation process can be divided into three critical steps: tissue procurement and preservation; isolation, culture and shipment; and graft transplantation and monitoring. To begin, whole organ oxygen consumption rate (WOOCR) measurements are presented for the assessment of organ viability, followed by the description of new techniques for improving the efficacy of pancreas cooling during procurement, and the use of hypothermic machine perfusion (HMP) to improve pancreas preservation. These methods can be used to qualify biological tissue products and to evaluate and improve organ procurement and preservation. Next, HMP combined with silicon-rubber-membrane (SRM) culture systems are presented as techniques to improve the quality of tissues isolated from juvenile porcine pancreata, and advanced nutrient supplementation with suspension culture systems are shown to improve β-cell expansion. Finally, 19F-MRS oximetry techniques are presented for non-invasive oxygen monitoring of tissue-engineered grafts (TEGs), and these techniques are further applied to develop, implement, and validate a novel method for oxygen delivery to an implanted tissue-engineered islet grafts.
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    Programmed death-1 regulates islet-specific lymphocytes in type 1 diabetes
    (2018-12) Martinov, Tijana
    Programmed death-1 (PD-1) is a T cell inhibitory receptor important for tolerance maintenance. PD-1 is highly expressed on chronically stimulated T cells, such as those specific for persistent viral or tumor antigens. PD-1 pathway blockade revolutionized cancer therapy in recent years. While response rates are higher than with chemotherapy, not all patients respond, and some develop autoimmune-like symptoms, or even overt autoimmunity. Herein, I sought to understand how the PD-1 pathway regulated islet-specific CD4+ T cells during type 1 diabetes (T1D) progression in non-obese diabetic (NOD) mice. Since insulin itself is one of the main antigens driving T1D, we developed insulin peptide:MHCII tetramer reagents to track insulin-reactive CD4+ T cells. Insulin-specific CD4+ T cells that expressed the most PD-1 also had the highest affinity for self, suggesting that PD-1 preferentially regulated those cells with the highest autoimmune potential. In NOD mice, the majority of insulin-specific CD4+ T cells had an anergic (tolerant) phenotype, but surprisingly, PD-1 blockade did not override the anergy program. These findings suggested that the differentiation state of the CD4+ T cell pre-determine its susceptibility to PD-1 blockade. Autoantibody production is a hallmark of autoimmunity, and has also been reported in patients treated with PD-1 blockade, suggesting that PD-1 might regulate this process. Autoantibody production results from B cell:CD4+ T cell interactions in the germinal center of the lymph node. The dynamics and regulation of the germinal center in spontaneous autoimmunity and after PD-1 blockade are not well understood, primarily due to an inability to track self-specific lymphocytes. To bridge this knowledge gap, we used tetramers to phenotype islet-specific CD4+ T cells and B cells in mice. PD-1- or PD-L1-deficient mice, as well as NOD mice treated with anti-PD-1, had increased insulin autoantibodies, as well as increased insulin-specific T follicular helper CD4+ T cells and germinal center B cells compared to controls. This increase was dependent on CD4+ T cell-intrinsic PD-1 signaling and relied on peptide:MHCII recognition. Taken together, my thesis work provides a mechanistic explanation for autoantibody onset following PD-1 blockade in the clinic, and has important implications for cancer immunotherapy and autoimmunity.
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    Risk Factors for Abdominal Aortic Aneurysm and Larger Infrarenal Aortic Diameters in a General Population
    (2018-07) Yao, Lu
    Abdominal aortic aneurysms (AAAs) comprise an important public health issue, which could be reduced by primary prevention. Identifying AAA risk factors is critical for developing effective preventive strategies. Previous epidemiologic studies have suggested that some risk factors for atherosclerotic cardiovascular disease are also associated with increased risk of incident AAAs, including advanced age, male gender, white race, greater height, smoking, hypertension, dyslipidemia, and some biomarkers related to inflammation and hemostasis. Some observational studies showed an inverse relationship between diabetes and AAA; while others did not show an association. The inverse relationship between diabetes and AAA is considered counterintuitive in the context of diabetes being a risk factor for various cardiovascular diseases. To better understand the etiology of AAA, further investigation on the relation between atherosclerosis and AAA is warranted. Also, the relation between diabetes and AAA needs to be studied further. With the exception of screening studies where AAAs were defined commonly as a maximum infrarenal aortic diameter (IAD) ≥ 3 cm, in most existing epidemiologic studies, AAAs were obtained through medical records and death certificates. This approach ascertains clinical AAAs that were either symptomatic or at least clinically detected. However, large screening studies have suggested that most AAAs are asymptomatic, even though aortic size often expands rapidly and many asymptomatic AAAs may eventually become symptomatic. Furthermore, an increased IAD between 2.3 and 3 cm has been associated with higher risk of future AAA and other cardiovascular events. Thus, examining the determinants of elevated IADs (i.e. IAD ≥ 2.2) among individuals without clinical or asymptomatic AAAs is potentially important to the prevention of AAAs. Manuscript 1 examined the associations of carotid atherosclerosis and stiffness with later AAAs in ARIC. We used carotid intima-media thickness (1987-1992) and atherosclerotic plaque (1987-1989) as indices of carotid atherosclerosis, and used carotid Beta Index (1990-1992) to represent carotid distensibility. We identified 542 incident, clinical AAAs during follow-up through 2011 using hospital discharge codes, Medicare outpatient diagnoses, or death certificates during 22.5 years of follow-up. After multivariable adjustment, the presence of carotid atherosclerotic plaque at baseline was associated with 1.31 (95% CI: 1.10 - 1.57; P: 0.003) times higher risk of clinical AAA. Greater carotid intima-media thickness and Beta Index were also associated with clinical AAA with a dose-response across quartiles (P trend for both: 0.006; hazard ratios [95% CI] for the highest vs. lowest quartiles: 1.55 [1.13 - 2.11] and 1.68 [1.16 - 2.43], respectively). The results suggest that indices of greater carotid atherosclerosis and lower carotid distensibility are markers of increased AAA risk. Manuscript 2 explored risk factors for an elevated IAD (IAD ≥ 2.2 cm) in the absence of AAA in 5620 ARIC participants who attended an abdominal ultrasound screening in 2011-2013. We assessed a variety of risk factors and created derived variables to capture their long-term cumulative effects (over 1987-2013). In the model with adjustment for AAA risk factors, men (vs. women) had 2.50 (95% CI: 1.90, 3.28) times higher odds of having an elevated IAD, and participants with long-term diabetes (vs. non-diabetics) had 0.52 (0.35, 0.77) times lower odds. Height, waist circumference and smoking pack-years were positively associated with elevated IADs [ORs (95% CI) for the highest vs. lowest quintiles of each risk factor: 1.93 (1.36, 2.75), 1.67 (1.28, 2.19) and 1.62 (1.26, 2.08), respectively]. Other factors were not associated with elevated IAD. In summary, male sex, smoking, greater height, larger waist circumference and not having diabetes were associated with elevated IAD among persons without an AAA. The findings highlight the potential for primary prevention of AAA through control of these factors. Manuscript 3 represents a meta-analysis of prospective cohort studies and case-control studies to examine further the relation between diabetes and AAAs. We searched for English literature from online database search (MEDLINE (1966-), EMBASE and Web of Science) plus a manual examination of references in selected articles as of Feb 2018, and included a total of 12 cohorts with 11,410 AAAs in 2,665,121 adult participants and 4 case-control studies with 1,065 AAAs and 12,074 controls who met pre-determined eligibility criteria in the meta-analyses. A DerSimonian and Laird random effects model pooled association estimates and their 95% confidence intervals from studies. Diabetes was inversely associated with the risk of AAA (pooled relative risk: 0.56; 95% confidence interval: 0.50 - 0.63). Results were similar in the subgroup analyses by sex (male/female), setting (population/clinical), and study design (cohort/case-control). In summary, in contrast with diabetes being a risk factor for most cardiovascular diseases, diabetes appears to be strongly and inversely associated with the risk of AAA. In summary, my dissertation studies filled a gap of literature and further assessed AAA etiology by completing the three manuscripts. The three studies have potential to improve understanding of the etiology and early prevention of AAAs at the population level. Findings from my dissertation studies may offer a strategy to clinically identify high-risk individuals.
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    The Role of Clinical Pharmacists in Modifying Cardiovascular Disease Risk Factors
    (University of Minnesota, College of Pharmacy, 2014) Bagwell, Autumn; Skelley, Jessica W.; Saad, Lana; Woolley, Thomas; Dugan, DeeAnn
    Objective: Assess the effect of intensive clinical and educational interventions aimed at reducing risk factors for Cardiovascular Disease (CVD), implemented by clinical pharmacists, on modifying risk factors in targeted patients at high risk for CVD. Design: Patients with at least two risk factors for CHD were identified at two clinics by conducting a pre-intervention survey and were monitored over a period of 6 months with follow up conversations conducted every 4 weeks by phone and at subsequent physician visits. A post-intervention survey was conducted at the end of the study period to detect modified risk factors. Setting: The Jefferson County Public Health Department (JCHD) Participants: We followed a total of 47 patients over 6 months. The average age at baseline was 51 years old and 80% of the participants were female. The baseline average number of modifiable cardiovascular disease risk factors was 3.7. Measurements: We assessed total number of CVD risk factors, smoking behavior, blood pressure, LDL, A1C, weight, and level of physical activity (major modifiable risk factors by the American Heart Association). Results: Over a 6 month follow-up of 47 patients, statistically significant reductions occurred in total number of CVD risk factors, systolic and diastolic blood pressures, and A1C. Reductions also occurred in LDL level, weight, and changes in smoking behavior and physical activity were identified. Conclusions: Results showed that increased patient counseling on adherence and lifestyle changes along with increased disease state monitoring and medication adjustment led by a clinical pharmacist can decrease risk factors in patients with multiple risk factors for cardiovascular disease.
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    The role of mitochondrially derived oxidative stress in the development of insulin resistance in the adipocyte
    (2015-09) Olson, Dalay
    The number of people worldwide living with type-2-diabetes (T2D) is increasing at an alarming rate. In 2014, approximately 9% of the adult population worldwide was suffering from diabetes, with greater than 90% suffering from the type-2 form of the disease. One prominent risk factor for the development of T2D and insulin resistance is obesity. Ninety percent of type-2-diabetics are overweight or obese, highlighting the striking link between the two diseased states. Although T2D has been studied for years, the underlying mechanisms outlining the development of obesity induced insulin resistance remain poorly understood. Currently, it is well established that adipose tissue inflammation plays a major role in the induction of insulin resistance. Preliminary experiments using inflammatory cytokines to induce insulin resistance in adipocytes suggested that mitochondria maybe a site of oxidant accumulation resulting from transcriptional down-regulation of key mitochondrial antioxidants. Because oxidative stress is a hallmark feature of obese, insulin resistant adipose tissue, I was interested in identifying important metabolic pathways that were regulated by oxidative stress, independent of inflammation, within the adipocyte itself. Knockdown of Peroxiredoxin-3 (Prdx3) in adipocytes provided a tool that not only mimicked what was seen in diseased states, but also allowed for mechanistic study of the direct effects of mitochondrially generated oxidative stress on adipocyte insulin sensitivity. Importantly, these data revealed that silencing Prdx3 in adipocytes resulted in increased oxidative stress and insulin resistance mediated by rictor oxidation, decreased mTORC2 activity and subsequent decreases in S473-AKT phosphorylation.
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    Use of sibutramine (Meridia) in obese patients with Type 2 diabetes is associated with statistically significant weight loss and a decreased hemoglobin A1c
    (2008-10-16) Sandvig, Lisa
    Abstract: In a meta-analysis of 8 randomized controlled trials including obese patients with Type 2 diabetes, the addition of sibutramine to standard diabetes therapy resulted in a significant decrease in body weight and hemoglobin A1c.
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