京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12944号 / 論医博第2096号 / 新制||医||1010(附属図書館) / 32203 / 京都大学大学院医学研究科医科学専攻 / (主査)教授 川口 義弥, 教授 横出 正之, 教授 稲垣 暢也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19996号 / 工博第4240号 / 新制||工||1656(附属図書館) / 33092 / 京都大学大学院工学研究科電気工学専攻 / (主査)教授 土居 伸二, 教授 小林 哲生, 准教授 蛯原 義雄 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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Type 1 diabetes (T1D) is the result of the autoimmune-mediated destruction of the pancreatic beta-cells leading to the inability to produce insulin sufficiently and, in turn, regulate blood glucose levels. Abnormal levels of blood glucose, specifically hyperglycemia, have been linked to many diabetic complications, with Brownlee proposing decreased GAPDH activity and the resultant increase in four main pathways as the mechanism(s) leading to these complications. Though skeletal muscles play a major role in glucose uptake, they are believed to be relatively protected against these complications as they are able to regulate their glucose uptake. However, evidence is accumulating that skeletal muscles are adversely affected in T1D, particularly with respect to their mitochondrial function. This led us to consider that the skeletal muscles of those with T1D would experience substrate overload (high intracellular lipids and recurrent, high levels of intracellular glucose), which would initiate a negative spiral whereby substrate excess would damage mitochondria - leading to an impaired ability to utilize these substrates - further worsening the substrate overload. Therefore, the objective of this study was to investigate glycogen and intramyocellular lipid (IMCL) content in the muscles of mice and humans with T1D, as well as the potential downstream effects in the form of post-translational modifications (PTMs), mitochondrial content, and lipofuscin accumulation. The Akita T1D mouse model was used to assess substrate overload in uncontrolled diabetes, whereas human participants were used to investigate substrate overload in the presence of insulin therapy. Assessment of glycogen and IMCL content revealed no difference between controls and diabetic cohorts in both the rodent and human study, indicating the lack of substrate overload. Post-translational modifications did not significantly change between Akita and wild-type mice; however, there was a main effect of diabetes on acetylation levels within Akita mice. Lastly, most mitochondrial properties, except for subsarcolemmal pixel density, did not differ either between diabetic and non-diabetic subjects in the human study. Thus, despite mitochondrial complex impairments in diabetic subjects, its extent was not significant enough to cause alterations to the mitochondria as a whole and result in mitochondrial degradation and lipofuscin formation. This study has provided novel insight into the metabolic properties of skeletal muscle during diabetes. Although there was no indication of substrate overload, diabetes still resulted in some changes to PTM levels and mitochondrial pixel density. However, the effects of these changes did not significantly alter the muscle and resulted in pathway impairments of those that were studied. This could be due to an adaptive mechanism in mice, although future studies are needed to confirm this hypothesis. In the human study, healthy, well-controlled individuals could explain why there was hardly any difference seen, suggesting that controlling glycemic levels was imperative in preventing diabetic complications in muscle. / Thesis / Master of Health Sciences (MSc)

Background: The parents’ child with type 1 diabetes are responsible to make glucose measurements several times a day and by that have the primary responsibility for the child's health. This results in a new life for the parents. Aim: To describe parents' experiences to live and care for a child with type 1 diabetes. Method: A qualitative literature-based method by systematically searching through Pubmed and Cinahl about 10 selected articles. Results: The article revealed five main themes: Parents' increased responsibility, Parents' longing for a normal life, How the surroundings lack of knowledge affects you, The Healthcare system responsibility, Parents' painful emotions and feelings. Based on these five themes eleven sub themes emerged: The fight for a stable blood sugar level, Constant surveillance, Not limits the child’s daily activities, Parents' life change, School staff and friends' significant support, Constantly educating the surroundings, The importance of Care support, Your own need for knowledge, Continuous worries and fear, Feeling guilt over right treatment and care of the child, Inevitable exhaustion and burnout. Discussion: A nurse can learn a lot from the parents' experiences of living with a child diagnosed with type 1 diabetes and by that create valuable support for the parents. The discussion involves parents' worries and feelings of fear and guilt. The very important responsibility that the health care system has is discussed in relation to the parents. Mothers were mainly the ones who distributed the care of their child’s type 1 diabetes

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Type 1 diabetes [T1D] is an autoimmune disease that presents in a pathophysiological disorder as insulin deficiency. Managing this illness during childhood is a constant challenge of maintaining blood glucose levels within a healthy range, resulting in increased stress for children and caregivers. School attendance is one factor that may result in increased stress. Studies have highlighted the fact that teachers of students with T1D may receive little education regarding management of the disease and may be required to make accommodations which can result in confusion, miscommunication, and increased psychosocial stress. The goal of this research was to learn about the experiences of teachers of students with T1D, what is expected of them, what resources they have, and factors which they perceive as barriers or facilitators to education for students with T1D. Semi-structured interviews were conducted with two high school teachers in East Tennessee who had experience teaching students with T1D. The results of the interviews showed that teachers receive limited education, that they are expected to make accommodations such as having snacks on hand and allowing extra access to phones, and that there are perceived barriers to education of individuals with T1D due to the possibility of life-threatening events. The teachers reported that school nurses are involved in the care of students with T1D. Limitations include that only two teachers were interviewed, and while the results are important to take into consideration, saturation was not reached. Future research could include more in-depth interviews or surveys with school nurses.

Bakgrund Typ 1-diabetes (T1D) är en av de vanligaste kroniska sjukdomar som drabbar barn över hela världen. Det är inte bara barnet som påverkas utan hela familjen påverkas när barn får T1D. T1D innebär livslång egenvård och det är föräldrarna som har det största ansvaret när det gäller barn. Sjuksköterskan har ett ansvar att stödja, vägleda samt ge information kring hanteringen av sjukdomen till både barnet och föräldrarna. Syfte Syftet är att beskriva hur livet för föräldrarna påverkas av att ha ett barn diagnostiseratmed typ 1-diabetes. Metod Denna studie har genomförts som en strukturerad litteraturstudie med inslag av den metodologi som används vid systematiska översikter. 13 kvalitativa artiklar har analyserats. Resultat Resultatet delades in i fyra huvudkategorier och tolv underkategorier som besvarade studiens syfte; Behov av kunskap och stöd, Förtroende och ansvar saknas, Leva med konstant oro och beredskap genom barnets uppväxt och Anpassning till den nya verkligheten. Slutsats Resultatet visade en brist på stöd och information från sjukvården. Denna studie ger en ökad förståelse för hur föräldrarnas liv påverkas när barnet diagnostiseras med T1D. För att sjuksköterskan ska kunna ge en bra omvårdnad är förståelse och empati av vikt för attbarnet skall uppnå en optimal hantering av T1D. / Background Type 1 diabetes (T1D) is one of the most common chronic diseases affecting children worldwide. It is not only the child who is affected, but the whole family is affected when children get T1D. T1D involves lifelong self-care and it is the parents who have the greatest responsibility when it comes to children. The nurse has a responsibility to support, guide and provide information about the management of the disease to both the child and the parents. Aim The aim is to describe how the lives of the parents are affected by having a child diagnosed with type 1 diabetes. Method This study has been conducted as a structured literature review with elements of the methodology used in systematic reviews. 13 qualitative articles have been analyzed. Results The results were divided into four main categories and twelve subcategories that answered the purpose of the study; Need for knowledge and support, Trust and responsibility are lacking, Living with constant worry and preparedness through the child's upbringing and Adaptation to the new reality. Conclusions The results showed a lack of support and information from the healthcare system. This study provides an increased understanding of how the parents' lives are affected when the child is diagnosed with T1D. In order for the nurse to be able to provide good care, understanding and empathy are important for the child to achieve optimal handling of T1D.