<p>The increased recognition of chronic disease (CD) has been accompanied by an era of medical technology, intended to better treat and manage CDs such as type 1 diabetes. Since the discovery of insulin in 1921, the treatment and management of type 1 diabetes has significantly improved, and witnessed innovations such as the insulin pump. Yet, as the population ages within a technological society, the implications of advancements in diabetes care and its relationship with older adults is of great concern. How do older adults identify and make use of these new technologies? How do technological advances challenge traditional life course models or expected transitions of growing old? How do older adults continue to cope and manage with a CD in their advanced years? The objective of this study was to explore how older adults with type 1 diabetes relate to management devices used in their daily routines. Five open-ended and semi-structured interviews were conducted with older adults living with type 1 diabetes (recruited through the Canadian Diabetes Association [CDA] and the Hamilton Health Sciences [HHS] Diabetes Care and Research Program [DCRP], Hamilton, Ontario). Interviews were transcribed and analyzed drawing on analytic techniques of grounded theory. Open, axial and selective coding was used in accordance to the constant comparative approach. Themes included living longer with type 1 diabetes, how type 1 diabetes challenges traditional models of aging and the lifecourse perspective, and older adults welcoming the use of technology. Overall findings suggested technology used for the daily treatment and management of type 1 diabetes may permit increases in one’s quality of life (QOL), yet challenge policies and practices within healthcare settings to ensure older adults maintain independent self-management strategies.</p> <p>Keywords: aging, chronic disease, technology, treatment, type 1 diabetes, older adult, diabetes community</p> / Master of Arts (MA)

Rates of immune-mediated diseases (IMDs) have rapidly increased. Although the exact etiology has not yet been fully elucidated, disruptions to the microbiome has been proposed as a potential mechanism. We conducted a retrospective, longitudinal, birth cohort study utilizing electronic health records (EHR) to investigate the association between early life antibiotic exposure and the risk of developing juvenile idiopathic arthritis (JIA), pediatric psoriasis, or type 1 diabetes. Incident rate ratios (IRR) were estimated using modified Poisson regression models and adjusted for significant confounders. Children exposed to two or more antibiotics prior to 12 months of age had a 69% increased risk of developing JIA (1.69 IRR, 95% CI [1.04-2.73]), which rose to 97% when exposed prior to 6 months (1.97 IRR, 95% CI [1.11-3.49]). Children exposed to a penicillin antibiotic had a 62% increase in risk for psoriasis (1.62 IRR, 95% CI [1.06-2.49]), which rose slightly to 64% when exposure occurred between 6 and 12 months of age [(1.64 IRR, 95% CI [1.04-2.59]). We found a moderate to strong association between early antibiotic exposure and risk for JIA and psoriasis when exposure was examined by age, frequency, and type of antibiotic, but not for type 1 diabetes. Potential interactions effects between infection and antibiotics with an increased susceptibility to early life infections among children with an IMD was also observed. Overall, children exposed to antibiotics at an early age have an increased probability of developing an IMD after 12 months of age. However, alternative explanations for this association should be considered. / Public Health

Bakgrund: Diabetes mellitus typ 1 är en autoimmun sjukdom där antalet insjuknade ökar för varje år. Att vara ung vuxen med en kronisk sjukdom kan leda till omställningar när det nya självständiga livet och sjukdomen behöver samverka. Syfte: Att belysa unga vuxnas erfarenheter av att leva med Diabetes mellitus typ 1. Metod: En kvalitativ litteraturstudie utfördes. Databassökning genomfördes i CINAHL och PubMed. Åtta kvalitativa studier granskades enligt Olsson och Sörensens mall för kvalitativa studier. Analysen utfördes med hjälp av Popenoe et al. (2021) analysmodell.  Resultat: Resultatet sammanställdes i tre huvudkategorier och åtta subkategorier. Att hantera sin egenvård upplevdes utmanande, rädslor för hypoglykemi gjorde att många misskötte sin diabeteshantering. Att känna sig annorlunda gjorde att strävan efter ett liv utan diabetessjukdomen var stor, där olika hanteringsstrategier hjälpte att successivt bearbeta acceptansen. Slutligen, stöd från anhöriga och närståendes men även från sjukvårdspersonalen var betydelsefullt. Konklusion: Unga vuxna upplevde sig vara i en fas i livet där de ständigt ställs inför nya utmaningar. Att dessutom ha en kronisk sjukdom upplevdes leda till ytterligare utmaningar och omställningar i livet att anpassa sig till. Omvårdnaden inkluderar att främja personens helhet, stödja delaktigheten och hitta strategier för egenvårdshantering. / Background: Type 1 diabetes mellitus is an autoimmune disease where the incidence of diagnosis increases annually. Being a young adult with a chronic disease can lead to readjustment when the new independent life and disease need to cooperate. Aim: To illuminate young adults' experience of living with type 1 diabetes mellitus. Methods: A qualitative literature study was performed. Database searches were done through CINAHL and PubMed. Eight qualitative studies were reviewed using Olsson and Sorensen’s assessment template for qualitative studies. The analysis method was accomplished by means of Popenoe et al. (2021) analysis model.  Results: The result was compiled into three main categories and eight subcategories. Manage self-care were perceived as challenging where fear of hypoglycemia led to miss care of diabetes management. To feel different increased the aspire for life without diabetes, where different management strategies were a successive help for acceptance. Finally, support from relatives and healthcare professionals was perceived as meaningful. Conclusion: Young adults experienced a phase in life where they constantly faced new challenges. Having a chronic disease leads to further challenges and readjustments in life to adjust to. Nursing care includes encouraging the person as a whole, supporting participation, and finding strategies for self-care management.

Bakgrund: Diabetes mellitus typ 1 är en kronisk sjukdom vilken medför stora omställningar i livet för både barn och föräldrar. Föräldrar har huvudansvaret för egenvården när deras barn får DMT1 och det ger dem ett stort ansvar att strukturera upp rutiner och få vardagen att gå ihop. Sjukdomen kräver livslång insulinbehandling och det finns risk för hypo- eller hyperglykemi. Syfte: Syftet var att beskriva föräldrars upplevelser av stöd när deras barn lever med diabetes mellitus typ 1. Metod: En litteraturbaserad studie baserad på 12 vetenskapliga kvalitativa artiklar med föräldraperspektiv. Resultat: Ur analysen framträdde två huvudteman; stärker föräldrars självtillit och brister som bidrar till ökad oro, med sju underteman. Konklusion: Stöd stärker föräldrars självtillit. Telefonen ger föräldrarna trygghet då de snabbt kan få kontroll över svårhanterbara situationer genom att ringa till sjukvårdspersonal. Föräldrar upplever stort stöd i att dela erfarenheter med andra i samma situation. Föräldrar upplever att brister i stödet bidrar till en ökad oro. Föräldrar upplever att okunskap hos skolpersonal och anhöriga skapar en rädsla för deras barns säkerhet och gör det svårt för dem att få avlastning på lång sikt. / Background: Type 1 diabetes mellitus is a chronic condition causing significant life adjustment for both children and parents. Parents bear the primary responsibility for self-care when their child has type 1 diabetes mellitus, necessitating routine structuring and daily life management. The disease requires lifelong insulin treatment, with risk of hypo- or hyperglycemia. Aim: To describe parents’ experiences of support when their child lives with type 1 diabetes mellitus. Method: A litterateur-based study based on 12 articles with qualitative approach. Findings: From the analysis two themes were identified; Strengthens parents' self-confidence and deficiencies that contribute to increased with seven subthemes. Conclusion: Support strengthens parents' self-confidence. The phone provides parents with reassurance as they can quickly gain control over challenging situations by contacting healthcare professionals. Parents feel significant support in sharing experiences with others in similar situations. Parents perceive that deficiencies in support contribute to increased anxiety. Parents perceive that ignorance among school staff and relatives creates fear for their children's safety and makes it difficult for them to obtain long-term relief.

B cells play crucial roles in the development of the two human autoimmune diseases, type 1 diabetes (T1D) and systemic lupus erythematosus (SLE). In the past decade, numerous studies showed positive responses of B cell depletion therapies in these two diseases. However, the beneficial effects are temporary and accompanied with adverse events. In this dissertation, we aimed to identify novel targets for a better modulation of disease development using mouse models. These diseases have circulating autoantibodies that are mostly mutated with an IgG isotype, indicating B cells that are producing them have been through the process of affinity maturation. Activation-induced cytidine deaminase (AID) is a core enzyme that regulates somatic hypermutation (SHM) and class switch recombination (CSR), the two key mechanisms in affinity maturation. We showed that genetic ablation of AID significantly inhibited the development of TID in NOD mice. Homologous recombination (HR) pathway is important for the repair of AID-induced DNA double strand breaks during CSR. 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid, also known as DIDS, is a small molecule that inhibits HR pathway and subsequently leads to apoptosis of class switching cells. DIDS treatment remarkably retarded the progression of TID, even when started at a relatively late stage, indicating the potential of this treatment for disease reversal. In both approaches, we observed a notable expansion of CD73+ B cells, which exerted an immunosuppressive role and could be responsible for T1D resistance. Next we examined the effect of targeting affinity maturation through these two approaches in lupus-prone mice. The genetic abrogation of AID in BXSB mice significantly ameliorated lupus nephritis and prolonged their lifespan. AID-deficient mice also exhibited improvement on disease hallmarks with increased marginal zone B cells and more normal splenic architecture. DIDS treatment notably reduced class switching when B cells were stimulated in vitro. However, the administration of DIDS did not strikingly alter the course of SLE in either BXSB mice or MRL/lpr mice. These findings demonstrated that affinity maturation could be a potential target for T1D and SLE, while further explorations into targeting other components in the repair pathway are warranted for SLE. Lastly, we assessed the effect of maternal AID modulation on the SLE development in the offspring using BXSB mouse model. Interestingly, the absence of maternal AID resulted in offspring that developed significantly more severe lupus nephritis compared to control. The offspring born to AID-deficient dams also exhibited elevated levels of pathogenic autoantibodies and exacerbated disease features. Therefore, the modulation of maternal AID could influence the SLE development in the offspring, and future investigations are needed to determine the underlying mechanisms responsible for the disease acceleration. / Doctor of Philosophy / The failure of the immune system to differentiate self from non-self leads to the development of autoimmune diseases. Type 1 diabetes (T1D) and systemic lupus erythematosus (SLE) are complex autoimmune diseases affecting millions of people in the world. Despite intensive research regarding these two diseases, no known cure is available indicating an imperative need for the development of novel therapies. With the importance of B cells in the pathogenesis of these two diseases, intensive research focused on whole B cell depletion therapies. However, these therapies exhibited high risks of infections as a result of depleting all the B cells. In this dissertation, we sought to selectively target specific B lymphocyte subsets that are crucial contributing factors in the development of T1D and SLE. While the effect of therapeutic treatment varied among different mouse models, the genetic manipulation of specific B cells successfully retarded the progression of both T1D and SLE and extended the lifespan of the mice. Further studies shed light on the possible mechanisms that are responsible for the disease inhibition. These data proved that targeting specific B cell compartment could be a potential disease management in T1D and SLE patients. In addition, using the established mouse model, we demonstrated the modulation of maternal factors significantly impact the SLE development in the offspring. Future experiments to identify the underlying mechanisms could provide more targets for the therapeutic development.

The ability of human pluripotent stem cells (hPSCs) to differentiate into different types of cells has been regarded as a significant discovery in the development of cell replacement therapy for type 1 diabetic patients. MicroRNAs can be transported to recipient cells via vesicles, so-called exosomes. Exosomal microRNA differ from those of the parent cells suggesting that cells possess an active selecting mechanism of exosomes and their contents. Therefore, microRNAs may directly or indirectly regulate the expression of pancreatic islet-specific transcription factors to control the differentiation and maturation of pancreatic islet cells. In this study, the dynamic expression of exosomal and intracellular microRNAs from human pancreatic islets were analyzed and were compared with that in stem cell-derived islet-like clusters. The study also aimed to analyze the expression levels of intracellular microRNA in human pancreatic islets and stem cell-derived islet-like clusters compared to exosomal microRNA extracted from human islet media and stem cell media, respectively. The primary method of exosome extraction was ultracentrifugation, followed by microRNA isolation using a kit. The exosomes were then characterized with NTA, and the isolated microRNAs were detected using RT-qPCR. The results showed that the expression of microRNAs was generally low in human islets compared to isolated exosomes. The microRNA expression levels in stem cell-derived islet-like clusters and their respective isolated exosomes were also analyzed and it showed that let-7a, miR-375 and miR-26a were more abundant in exosomes. The results can contribute to the generation of more functional stem cell-derived islet-like cell clusters prepared from hPSCs to some extent. However, continued research in this area is required.

Diabetes is a significant health burden worldwide. The most common types of diabetes, type 1 and type 2 diabetes are typically characterized by complete insulin deficiency and varying degrees of insulin deficiency, respectively. Glycated hemoglobin (HbA1c), formed when hemoglobin and glucose combine through glycation, can be used to monitor treatment in diabetic patients, and thus prevent future complications of the disease. HbA1c can be measured using point-of-care (POC) instruments, providing rapid results and immediate feedback on HbA1c levels. Measurement with POC instruments can reduce the need for additional visits for blood sampling, thereby lowering costs for both patients and healthcare systems. The main purpose of this study was to verify HbA1c on the POC instruments QuikRead Go and DCA Vantage by comparing the results with the reference method Cobas Pro and by comparing capillary and venous blood samples. The study utilized 30 venous patient samples, including 20 samples already analyzed on Cobas Pro and 10 samples collected venously and capillary from volunteer individuals. The coefficient of variation (CV) for QuikRead Go fell within the quality goal, while DCA Vantage exceeded the goal. The results demonstrated good agreement between capillary blood samples analyzed on POC instruments and venous samples analyzed on Cobas Pro. However, a statistically significant difference was found comparing venous samples analyzed on POC instruments and Cobas Pro. The results suggest that capillary sampling should be used for analysis on POC instruments. Certain limitations of the study should be considered when using QuikRead Go and DCA Vantage in practice.

Bakgrund: Incidensen för typ 1-diabetes ökar under barndomen vilket betyder att allt flera ungdomar kommer att genomgå överföringen från barndiabetesmottagningen till vuxendiabetesmottagning. Syfte: Syftet med uppsatsen var att belysa upplevelsen av överföringen från barndiabetesmottagning till vuxendiabetesmottagning ur olika perspektiv. Metod: En kvalitativ metasyntes. Sökningar gjordes på databaserna CINAHL och PubMed. Nio artiklar som svarar på författarnas syfte hittades, åtta kvalitativa och en mixed-method. Resultat: Fyra huvudteman identifierades: utmaningar att navigera, stödets funktion, inför överföringen till VDM och förväntningar. Vidare identifierades undertema för tre av huvudteman. Underteman till utmaningar att navigera var: ungdomarnas många utmaningar att navigera livet med T1D och vårdnadshavarnas utmaningar att navigera en ny roll. Underteman till inför överföringen var: tidigare förbereda överföringen och utbildning och upprepning av grunderna. Underteman till förväntningar var: innan överföringen och efter överföringen. Slutsats: Ungdomar genomgår en stor förändring i livet och den sena tonårstiden är präglad med stora förändringar och beslut. Överföringen från barndiabetesmottagning till vuxendiabetesmottagning utgör en extra sårbar tid för ungdomarna. Resultatet visar på att både ungdomarna och vårdnadshavarna uttrycker stor oro och ångest inför överföringen. Det är viktigt att diabetessjuksköterskan tidigt börjar förbereda ungdomarna och vårdnadshavarna inför överföringen för bästa möjliga resultat för alla inblandade. Ungdomarna uttrycker stor önskan om att få repetition och utbildning i grunderna inom diabetes. / Background: The incidence of type 1 diabetes increases during childhood, which means that more and more adolescence will undergo the transfer from the pediatric diabetes clinic to the adult diabetes clinic. Aim: The purpose was to highlight the experiences of transferring from pediatric diabetes clinic to the diabetes clinic from different perspectives. Method: A qualitative meta-synthesis. Searches were made on the databases CINAHL and PubMed. Nine articles that answered the authors' purpose were found, of which eight were qualitative and one were mixed-method. Results: Four main themes were identified: challenges to navigate, the function of support, before the transfer and expectations. Furthermore, sub-themes were identified from three of the main themes. The sub-themes of challenges to navigate were: the youth's many challenges navigating life with T1D and the caregivers' challenges navigating a new role. The sub-themes for before the transfer were: earlier preparing the transfer and education and repetition of the basics. The sub-themes of expectations were: pre-transfer and post-transfer. Conclusion: Adolescence undergoes big changes in their lives and late adolescence is marked by big changes and decisions. The transfer from pediatric diabetes clinic to the adult diabetes clinic constitutes an extra vulnerable time for the adolescents. The results show that both the adolescents and the guardians express great concern and anxiety before the transfer. It is important that the diabetes nurse starts preparing the adolescent and their guardians early on for the transfer for the best possible outcome for everyone involved. The young adolescent expressed a great desire to receive repetition and training in the basics of diabetes.

Type 1 diabetes (T1D) is regarded as an autoimmune disease. Beta cells, which produces insulin in pancreas are attacked by islet cell antibodies (ICA). This leads to gradual destruction of the beta cell, which in turn cause high level of glucose in the blood because the regulator "insulin" has disappeared. In that case the patient needs to be treated lifelong with insulin. It has been shown that the ICA reactivity consisting of reactivities against different autoantigens such as: insulin autoantigen (IAA), glutamic acid autoantigen (GAD), insulinoma antigen-2 autoantigen (IA-2) and most likely also zinc transporter autoantigen (ZnT8). Determination of ICA in serum samples is important for the classification of diabetes, prediction of T1D and the development of autoimmune therapies. Nowadays screening of ICA is performed with ”Medipan ICA screen” which is a commercial enzyme- linked immunosorbent assay (ELISA). Positives samples are further analysed by ELISA with the indirect immunofluorescence method (IF) to ensure a final positive answer. The purpose of this study was to evaluate and compare a new commercial ELISA kit ”RSR 2screen” with the Medipan ICA screen for use it in routine analysis to evalute if it has the same / higher specificity and sensitivity, and lower price compared with Medipan ICA screen. Serum samples from a control group (n = 199) and a patient’s group diagnosed with T1D (n = 100 were analyzed with both ELISA methods. The results were statistically evaluated to set a threshold value for positivity and to evaluate the method's sensitivity and specificity. The result showed that both ELISA- methods gave the same sensitivity (93%) and specificity (97.5%) and a high concordance (98.7%) was achieved. Analytical price per sample for the RSR 2screen was 4.2% lower than for the Medipan ICA screen. RSR 2screen can be used instead of Medipan ICA screen.

Ce travail de thèse s’est attaché à comprendre le lien étroit entre les dérégulations métaboliques et les dérégulations du système immunitaire, dans le cadre du modèle de diabète auto-immun de la souris NOD. Nous avons constaté que les bezafibrates protègent les souris NOD du diabète. Nous avons mis en évidence que ceci était lié à une diminution de l’infiltration des ilots beta du pancréas par les lymphocytes et cellules présentatrice d’antigen (CPA). La diminution d’IL-6 dans le sérum des souris traitées suggère une diminution générale de l’inflammation. Aussi, nous avons évalué l’implication du traitement en dehors du système immunitaire, en l’occurrence sur le stress cellulaire et la survie des cellules beta des ilots de Langherans, en utilisant une méthode de streptozotocine à faible dose, et nous avons observé une protection des souris traitées par les bezafibrates. Dans une deuxième partie de l’étude, nous avons observé qu’il existait au niveau du système immunitaire inné une surexpression des Toll-like récepteurs (TLR) 1, 2 et 6 dans les souris NOD comparées aux souris contrôles C57BL/6, ceci au niveau transcriptionnel ainsi qu’au niveau traductionnel. Nous avons ensuite démontré que cette surexpression avait une légitimité fonctionnelle. En effet, les CPA sécrètent plus d’Interleukine 6 (IL-6), et les cellules B, plus d’Immunoglobuline M (IgM). Nous avons poursuivi notre étude en modulant le contenu sérique en lipides dans nos souris NOD, en utilisant un régime gras pour augmenter la lipidémie et des bezafibrates hypolipidémiantes. Nous n’avons pas observé de modulation majeure de l’expression de TLR2 et TLR6, mais il est à noter que les CPA issues des souris soumises au régime gras sont plus susceptible à la réponse au ligand synthétique FSL-1 de TLR 2/6, qui sécrètent alors plus d’IL-6 que les NOD contrôles ou traitées aux bezafibrates. Nous avons pu ainsi souligner l’importance des liens entre le métabolisme et le système immunitaire, dans l’apparition de la maladie auto-immune que constitue le diabète de type 1. / In this thesis we sought to understand the link between metabolic deregulation and immune deregulation in the context of the NOD mouse autoimmune model. We observed that bezafibrates protect NOD mice from type 1 diabetes (T1D). We showed that pancreas beta islet infiltration by lymphocytes and APCs was diminished. IL-6 decrease in bezafibrate treated mice serum suggested a general dampening down of inflammation. Besides we evaluated the effect of bezafibrate out of the immune system by using a low-dose streptozotocin method and we observed that bezafibrate mice treated were protected. In a second part of this study we observed an overexpression of Toll-like receptors (TLR) 1, 2, 6 in NOD mice compared to C57BL/6 controls. This was noticeable at the transcription and translation level. We showed that this overexpression had a functional role. Indeed APCs from NODs secreted more IL-6, and B cells secreted more IgM when stimulated with corresponding ligands. We then modified the lipid content of NOD mice by using bezafibrates to decrease lipidemia, and a high fat diet (HFD) to increase lipidemia. No modulation of TLR2 and TLR6 expression was observed. However, APCs from HFD mice were more susceptible to TLR2/6 ligand FSL-1 stimulation by secreting more IL-6 than control or bezafibrate treated NODs. We here highlight the important links existing between metabolism immunity in the autoimmune T1D onset