Introduction: Women possess characteristics and experiences unique and different from men. Menstruation, pregnancy, puberty and menopause may present challenges for self-management, a prerequisite for those living with Type 1 diabetes mellitus (T1DM). The meaning and experiences of self-management have not been adequately explored from a young woman’s perspective within the diabetes literature. Purpose of the Study: Blood glucose and glycosylated hemoglobin (HbA1c) values are keys for determining success in self-management among individuals living with T1DM; however, the values may enable feelings of vulnerability and worthlessness in individuals living with T1DM. Through learning about the experiences of young women, it was hoped that the meaning of self-management would be uncovered. The research question was: What are the experiences of self-management among young women with Type 1 diabetes mellitus? Methods and Methodology: Descriptive phenomenology was used to uncover the experiences of self-management. Unstructured interviews with nine young women aged 22-30 years were conducted to uncover their lived experience. Data collection and analysis followed the methodical structure outlined by van Manen (1997). Findings: Data analysis revealed five themes, and the essence of participants’ self-management experiences. Identified themes included: 1) elusiveness of control; 2) the dualism of technology; 3) forecasting and establishing routines; 4) dealing with the “ups and downs”; and, 5) interface with the health care team. The essence that emerged from the data was “being in balance”. Conclusions: Self-management encompassed the desire and need to be in balance with one’s life and blood glucose levels. Self-management was something that evolved over time, and grew in complexity as phases progressed; it was something participants were still trying to grasp. Individual attitudes, goals, and self-management strategies dominated participants’ discourse in describing their hope of achieving and sustaining balance in their day-to-day lives. / Thesis (Master, Nursing) -- Queen's University, 2012-01-24 18:35:33.911

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While carotenoids are essential for visual function, their potential role in diabetic retinopathy is not known. By providing carrot powder, this study examined carotenoid metabolism and visual function in Type 1 diabetes. Wistar rats (n=30) were assigned to diet either with or without carrot enrichment (15%, w/w) for 12 weeks. Type 1 diabetes was induced with streptozotocin at 3 weeks. Retinal function and anatomical integrity were assessed along with retinoid and carotenoid levels in the serum, liver, and retina. Loss of ERG oscillatory potentials, with normal histology indicated early stage retinopathy. Healthy animals fed carrot diet showed highest b-wave amplitudes; reflecting higher phototransduction. Diabetic animals fed carrot diet had the lowest b-wave amplitudes, reduced retinoids liver reserves, and highest α- and β-carotene, suggesting disturbance of conversion during diabetes. Consequently carrot powder at concentrations used by this study cannot be recommended for diabetic retinopathy.

The aim of the study was to explore the role of autonomy in participants’ self-management of exercise behaviours and the transfer of responsibility throughout adolescence. The design of this study used qualitative description with information collected and presented using a case study approach. Participants were five emerging adults (aged 18–24) with Type 1 diabetes for a minimum of one year who lived in Canterbury. Data was gathered through three sources: a semi-structured interview seeking self-reported exercise throughout adolescence, a set of questionnaires based on four instruments, and physical activity performed over a week as recorded by an activity monitor. All participants achieved autonomy for exercise, however participants achieved autonomy at different ages. Participants’ diabetes self-management and physical activity levels varied according to their stage of life and lifestyle. They received varying advice about exercise from health professionals. Participants sought to determine their own exercise choices during adolescence, leading them to obtain a driver licence to be independent of parental transport. Three of the five met current guidelines for physical activity levels, and another met recommendations by her clinician. Policy implications regarding healthcare advice and barriers to exercise for young people are discussed, as are limitations of the research and future avenues for research.

La traduction d'une séquence nucléotidique d'ARNm dans plus d'un cadre de lecture est un phénomène découvert chez les virus vers la fin des années 1970. Depuis, quelques exemples de ce phénomène de traduction alternative ont été découverts chez l'humain dans les gènes INK4a, GNAS1, XBP1, et PRNP. La protéine alternative du gène GNAS , nommée ALEX, interagit et régule la protéine de référence et une mutation dans la protéine alternative peut engendrer certains phénotypes pathologiques. Plusieurs groupes de recherche ont effectué des analyses bio-informatiques sur le génome humain et ont suggéré que la traduction alternative de gènes pourrait être beaucoup plus importante que les quelques exemples connus à ce jour. Nous avons créé une base de données dans le but de prédire ces protéines alternatives à partir du transcriptome humain. Le gène ATXN1 semblait un candidat très intéressant à valider puisque la protéine de référence du gène, l'ATXN1, est impliquée dans une maladie neurodégénérative importante: l'ataxie spinocérébelleuse de type 1 (SCA1). Cette pathologie est causée par l'expansion d'une région CAG dans l'ADN qui est traduite en région polyglutamique. La protéine pathologique tend à agréger dans des inclusions nucléaires, ce qui induit l'altération de nombreux interacteurs de l'ATXN1 et pourrait interférer avec la fonction normale de ATXN1. Nous avons observé la présence de deux sites d'initiation alternatifs dans la séquence codante du gène ATXN1, situés dans le cadre de lecture +3. Expérimentalement, nous avons montré l'existence de deux isoformes de la protéine alternative nommée Alt-ATXN1, l'isoforme long étant fortement majoritaire. Alt-ATXN1, qui se localise dans le noyau, interagit de façon directe avec l'ATXN1 et coagrège avec celle-ci dans les inclusions nucléaires caractéristiques de la SCA1. Cette caractéristique intéressante suggère que la fonction biologique d'Alt-ATXN1 pourrait être altérée dans les cas de pathologie due à l'agrégation de l'ATXN1. Nous démontrons qu'Alt-ATXN1 lie les ARNm et possède une localisation nucléaire dépendante de la transcription, ce qui est caractéristique des protéines impliquées dans le processing de l'ARNm. L'existence d'Alt-ATXN1 a été confirmée in vivo dans une lignée neuronale humaine et dans des extraits de cervelets humains. Suite à ces découvertes, la fonction approfondie ainsi que la détermination du rôle d'Alt-ATXN1 dans la SCA1 demeurent sous investigation.

Transplantation of the islets of Langerhans is a promising technique for restoring the impairedinsulin production in brittle type 1 diabetics. The downside is that the patient will have to takeimmunosuppressant drugs in order to protect the islet cells from the immune system. Donorsare also sparse, making the quest of finding sufficient amounts of islets for transplantationhard. Encapsulation of the islets of Langerhans has been proposed as a means of protectingthe cells from the immune system taking away the need for immunosuppresives. The mostcommon encapsulation technique is extravascular capsules, which are categorized into micro-and macrocapsules. The microcapsules hold only one or a small set of islet whereas themacrocapsules hold a large quantity of islets.This thesis investigates the encapsulation impact on the beta-cells rapid insulin response torising plasma glucose levels. This was done by simulating the glucose-insulin system inMATLAB with included encapsulation of the islets. Two current macro-encapsulation set upswere used in the model, Beta-Air and ViaCyte devices, and they were compared against anormal case. The results showed that the Beta-Air device would not be able to restorenormoglycemia in a T1DM patient but rather showed a delay in insulin response, while theViaCyte device could mimic the normal case well.

Abstract Background: Patients diagnosed with Type 1 diabetes mellitus (T1DM) require insulin therapy. Although necessary, insulin therapy is associated with an immediate increase in Body Mass Index (BMI). Excessive increase in BMI may lead to obesity, which is associated with both short and long-term negative health outcomes. The objective of this study was to determine whether weight change in the six months after diagnosis in children and adolescents with T1DM is related to obesity status at age 18. Methods: Data from the Diabetes Education Resource for Children and Adolescents database was used for this study. This unique database combines extensive clinical information on each patient with virtually universal coverage. The study population comprised all children 2-18 years old diagnosed with T1DM by DER-CA endocrinologists in Manitoba between 1997 and 2012 (N=377). BMI z- scores calculated from measured height and weight were used to classify BMI group membership using the 2000 Centers for Disease Control growth charts. Regression models were used to assess the association between change in BMI z-score six months after diagnosis, and BMI z-score at last visit prior to transfer to adult care. The models controlled for BMI z-score at diagnosis, sex, pubertal status and length of follow up. Additional stratified analyses examined sub-groups within the sample, to determine whether the effects were different for children with different characteristics (e.g. sex and pubertal status at diagnosis). Results: At diagnosis, 9% of the study cohort was underweight, 68% normal weight, 15% overweight and 8% obese. Most, (91%) but not all patients gained weight in the six months after T1DM diagnosis and initiation of insulin therapy. The pattern of weight change differed by BMI group at diagnosis, sex, and pubertal status. At last visit, average BMI z-scores for all groups of patients were above zero, and varied less than BMI z-scores at diagnosis. Results of the multivariate analytic model (adjusted R2= 0.56) show that BMI z-score at diagnosis was most important, followed by female sex, change in BMI z-score in the six months after diagnosis, the interaction between BMI z-score at diagnosis and change in BMI z-score in the six months after diagnosis, and duration of follow up. Conclusion: Results of this study demonstrate that patients’ BMI group, sex, and pubertal status at diagnosis influenced the pattern of their BMI z-score change in the six months after diagnosis, and thereafter. Diabetic care teams may need to monitor not only the amount of weight change in the period after T1DM diagnosis, but also consider BMI at diagnosis.

While carotenoids are essential for visual function, their potential role in diabetic retinopathy is not known. By providing carrot powder, this study examined carotenoid metabolism and visual function in Type 1 diabetes. Wistar rats (n=30) were assigned to diet either with or without carrot enrichment (15%, w/w) for 12 weeks. Type 1 diabetes was induced with streptozotocin at 3 weeks. Retinal function and anatomical integrity were assessed along with retinoid and carotenoid levels in the serum, liver, and retina. Loss of ERG oscillatory potentials, with normal histology indicated early stage retinopathy. Healthy animals fed carrot diet showed highest b-wave amplitudes; reflecting higher phototransduction. Diabetic animals fed carrot diet had the lowest b-wave amplitudes, reduced retinoids liver reserves, and highest α- and β-carotene, suggesting disturbance of conversion during diabetes. Consequently carrot powder at concentrations used by this study cannot be recommended for diabetic retinopathy.

Background: Type I diabetes is a chronic disease that places great demands on the child and family. Parental involvement has been found to be essential for disease outcome. However, fathers’ involvement has been less studied, even though high paternal involvement has been correlated with less disease impact on the family and higher quality of life among adolescents. Aim: The overall aim of the study was to explore and analyze constructions of fathers’ involvement in their child’s everyday life with type 1 diabetes from an ecological and health promotion perspective. Four specific aims were applied: 1) explore and describe discourses in health care guidelines for children with type 1 diabetes in Nordic countries, focusing on parents' positioning (I), 2) analyze how Swedish pediatric diabetes teams perceived and discussed fathers’ involvement in the care of their child with type 1 diabetes, and to discuss how the teams’ attitudes toward the fathers’ involvement developed during a focus group process (II), 3) explore and discuss how fathers involved in caring for their child with type 1 diabetes experience support from their pediatric diabetes team in everyday life with their child (III), and 4) analyze how involved fathers to children with type 1 diabetes understand their involvement in their child’s daily life and to discuss their perceptions from a health promotion perspective (IV). Material and methods: A qualitative and inductive approach was applied. Data were collected and analyzed during 2010-2012. The sample consisted of three pediatric guidelines originating from Norway, Denmark and Sweden (I), three Swedish pediatric diabetes teams (PDTs) (II), and 11 (III) and 16 (IV) fathers of children with type 1 diabetes who scored high involvement on the Parental Responsibility Questionnaire. Data were collected through repeated focus group discussions with the PDTs (II), online focus group discussions (III) and individual interviews (III, IV) with the fathers. Three analysis methods were applied: analysis of discourses (I), Constructivist Grounded Theory (II, III) and content analysis (IV). Findings: The findings illuminated the complex interaction between the pediatric guidelines, the PDTs and the fathers. Fathers highly involved in their child’s daily life experienced different levels of tension between the general recommendations and their personal experiences of living with a child with type 1 diabetes (III). The fathers regarded their involvement in their child’s diabetes care as additional to their general parenting, and a fine balance was identified between a health promotion perspective and a controlling involvement. The common denominator between the highly involved fathers was their use of parental leave (IV). The PDTs initially perceived fathers’ involvement as gendered and balanced on the mother’s agement, but as focus was set on fathers’ engagement the PDTs increased their awareness of this and started to identify and encourage their engagement II). At the macro-level, parents’ voices were diminished in Nordic pediatric diabetes guidelines in favor of an expert discourse (I). Conclusions: Fathers’ involvement concerning a child with type 1diabetes is constructed in a complex way, based on an interaction between the fathers’ perceptions of their additional involvement and the support provided by the PDTs; the PDTs’ perceptions of the fathers’ involvement; and how parents/fathers are constructed in pediatric diabetes guidelines. In order to promote the health and well-being of children with type 1 diabetes, fathers’ involvement needs to be taken into account in the pediatric guidelines as well as in clinical practice.

Elevated plasma lipids are risk factors for cardiovascular disease (CVD). In certain conditions plasma lipids are normal yet individuals experience increased morbidity. Type 1 diabetes (T1D) is associated with elevated CVD despite normal lipids, while in liver failure low plasma lipids may indicate increasing hepatic damage. Plasma lipids can therefore belie underlying dysregulated lipid metabolism. Islet (ITx) or liver (LTx) transplants represent therapies for T1D and liver failure, respectively, but are associated with altered lipid metabolism attributed to immunosuppressive medications; however, causative mechanisms are unknown. Partial success of dietary therapy in post-transplant patients may be due to interventions limited in scope. Regulation of plasma lipids involve absorption, synthesis, and clearance. These studies examined lipogenesis and cholesterol synthesis using deuterium incorporation. In brittle T1D lipogenesis and cholesterol synthesis were similar to healthy controls; however hepatic lipogenesis and cholesterol synthesis tended to be lower in T1D compared to matched control subjects. Plasma cholesterol was lower and triglyceride similar in liver failure patients compared to controls. Lipogenesis was higher while cholesterol synthesis was lower in liver failure compared to controls. Disturbances in lipid synthesis may be influenced by underlying disease, such as hepatitis C. In ITx and LTx lipogenesis was lower whereas cholesterol synthesis was similar compared to controls. Lipid synthesis is therefore unlikely to contribute to post-transplant hyperlipidemia, inviting investigation of other mechanisms. Dietary intervention emphasizing fish oil, phytosterols, soy, fibers, and almonds lowered plasma lipids in controls but had mixed effects in transplant subjects. Reduction in plasma lipids occurred in transplant patients with higher baseline lipids, suggesting this intervention may be successful in hyperlipidemic patients; however the potential of this diet intervention requires further study in hyperlipidemic patients. Diet intervention lowered lipogenesis but did not significantly change 24h cholesterol synthesis in controls. Diet did not change 24h lipogenesis or cholesterol synthesis in transplant subjects. Plasma lipid response to dietary therapy was related to baseline cholesterol synthesis and to dietary compliance in transplant subjects. Further study is required to determine if cholesterol synthesis is predictive of response to diet. / Nutrition and Metabolism