Le diabète de type 1 (T1D) est une maladie auto-immune caractérisée par la destruction des cellules β du pancréas par les lymphocytes T auto-réactifs. Durant ma thèse, nous nous sommes intéressés au rôle des cellules de l’immunité innée dans le T1D à l’aide d’un modèle murin de la maladie : la souris NOD. Au contraire des cellules du système adaptatif (lymphocytes T et B), les cellules de l’immunité innée constituent la première ligne de défense de l’organisme lors d’une infection. Cette population est constituée entre autre de neutrophiles, cellules dendritiques plasmacytoïdes (pDC), macrophages, mais aussi de lymphocytes T et B non conventionnels tel que les cellules iNKT et B-1a. Précédemment, notre laboratoire a mis en lumière le rôle des lymphocytes iNKT dans le développement du T1D. Durant la première partie de ma thèse, nous avons démontré que les lymphocytes iNKT17, une sous-population des lymphocytes iNKT, ont un rôle délétère dans le T1D chez la souris NOD. Ces cellules infiltrent le pancréas et y produisent de l’IL-17, une cytokine pro-inflammatoire. Grâce à des expériences de transferts, nous avons mis en évidence que les lymphocytes iNKT17 exacerbent la maladie via la production d’IL-17. Dans la deuxième partie de ma thèse, nous nous sommes intéressés aux mécanismes qui induisent l’activation des lymphocytes T auto-réactifs. Nous avons observé chez la souris NOD, que la mort physiologique des cellules β conduit à l’activation de cellules de l’immunité innée : les neutrophiles, les lymphocytes B-1a et les pDC. La coopération entre ces cellules conduit à l’activation des pDC qui produisent de l’IFNα. Cette cytokine active les lymphocytes T auto-réactifs qui vont détruire les cellules β du pancréas. Nos résultats montrent que l’immunité innée est un acteur important dans la physiopathologie du diabète sucré. / The type 1 diabetes ( T1D ) is an autoimmune disease characterized by the destruction of β cells in the pancreas by autoreactive T lymphocytes. During my thesis, we are interested in the role of cells of innate immunity in T1D using a mouse model of the disease: NOD mice. In contrast to cells of the adaptive system (T and B lymphocytes ) cells of innate immunity is the first line of defense of the body during infection . This population consists of neutrophils , among other , plasmacytoid dendritic cells ( pDC ) , macrophages , T lymphocytes but not conventional B as iNKT cells and B -1a.Previously, our laboratory has highlighted the role of iNKT cells in the development of T1D . During the first part of my thesis , we demonstrated that iNKT17 cells, a subpopulation of iNKT cells, have a deleterious role in T1D in NOD mice . These cells infiltrate the pancreas and there produce IL -17 , a proinflammatory cytokine. Through transfer experiments , we demonstrated that lymphocytes iNKT17 exacerbate disease through the production of IL-17 . In the second part of my thesis , we investigated the mechanisms that induce the activation of autoreactive T lymphocytes. We observed in NOD mice , the physiological death of β cells leads to activation of innate immunity cells : neutrophils, lymphocytes B- 1a and pDCs . The cooperation between these cells leads to activation of pDC that produce IFNa . This cytokine activates autoreactive T cells which will destroy the β cells of the pancreas. Our results show that innate immunity is an important player in the pathogenesis of diabetes mellitus.

Abstract The incidence of childhood onset type 1 diabetes in Finland has been the highest in the world for several decades. Optimal management of the disease presents a lifelong challenge to the affected individuals. Related complications are common and include an ocular pathology called diabetic retinopathy. Type 1 diabetes with its ramifications can impact on several facets of a patient’s physical and psychological well-being. This study aimed to assess the ophthalmic findings and to evaluate the characteristics of general well-being of a population-based cohort of paediatric patients with type 1 diabetes and a population-based cohort of young adults with type 1 diabetes since childhood. The prevalence and risk factors of diabetic retinopathy were assessed of the population-based paediatric cohort in the catchment area of the Northern Ostrobothnia Hospital District and these were compared to a similar paediatric cohort studied 18 years previously. There was no significant change in the overall prevalence of diabetic retinopathy (12%) during the study period. Furthermore, glycaemic balance and other risk factors of diabetic retinopathy had remained almost unchanged. A population-based cohort of young adults was evaluated in 2007 for the prevalence and severity of diabetic retinopathy. Most of the cohort subjects (94%) had developed diabetic retinopathy and in every third subject there was evidence of proliferative retinopathy. Health related quality of life was the same as that in the age- and gender-standardised control population. For the most part, the young adults with a long duration of type 1 diabetes fared equally well as the general population in the measured social aspects. However, proliferative diabetic retinopathy was associated with lower educational achievements and poorer health related quality of life as well as with a higher probability of unemployment or being pensioned. Glycaemic balance and prevalence of diabetic retinopathy have remained unchanged in paediatric cohorts for nearly two decades despite concurrent advances in care. Social well-being was mainly restricted in young adults exhibiting signs of proliferative diabetic retinopathy. The negative impact of advanced complications of type 1 diabetes already in these young adults highlights the importance of strict metabolic control to maintain overall well-being. / Tiivistelmä Lapsuusiässä alkavan tyypin 1 diabeteksen ilmaantuvuus on ollut Suomessa maailman korkein usean vuosikymmenen ajan. Hyvän hoitotasapainon ylläpitäminen on elinikäinen haaste sairastuneelle. Diabeteksen liitännäissairaudet ovat yleisiä, kuten myös silmänpohjissa todettava diabeettinen retinopatia. Tyypin 1 diabetes voi komplikaatioineen vaikuttaa laajasti potilaan fyysiseen ja psyykkiseen hyvinvointiin. Tässä tutkimuksessa pyrittiin arvioimaan silmien terveydentilaa ja yleiseen hyvinvointiin liittyviä tekijöitä tyypin 1 diabetesta sairastavien lasten sekä lapsena diabetekseen sairastuneiden nuorten aikuisten väestöpohjaisissa potilasaineistoissa. Diabeettisen retinopatian esiintyvyys ja riskitekijät tutkittiin väestöpohjaisessa lapsipotilasaineistossa Pohjois-Pohjanmaan sairaanhoitopiirin alueella ja tuloksia verrattiin vastaavaan 18 vuotta aiemmin tutkittuun potilasaineistoon. Diabeettisen retinopatian esiintyvyys (12 %) ei ollut merkittävästi muuttunut tutkimusaikana. Glykeeminen tasapaino ja muut diabeettisen retinopatian riskitekijät olivat pysyneet kohorttien välillä oleellisilta osin ennallaan. Lapsena sairastuneiden nuorten aikuisten väestöpohjaisesta potilasaineistosta arvioitiin diabeettisen retinopatian esiintyvyys ja vaikeusaste vuonna 2007. Enemmistölle potilaista (94 %) oli kehittynyt diabeettinen retinopatia ja kolmanneksella todettiin proliferatiivinen retinopatia. Terveyteen liittyvä elämänlaatu oli verrattavissa ikä- ja sukupuolivakioituun verrokkiväestöön. Sosiaalista hyvinvointia mittaavat tulokset olivat pääosin yhtäläiset muuhun väestöön verrattuna. Proliferatiivisella diabeettisella retinopatialla havaittiin kuitenkin yhteys huonompaan terveyteen liittyvään elämänlaatuun ja koulutustasoon sekä korkeampiin työttömyys- ja eläköitymislukuihin. Tutkitussa aineistossa lapsipotilaiden glykeeminen tasapaino sekä diabeettisen retinopatian esiintyvyys pysyivät ennallaan lähes kahden vuosikymmenen ajan hoitojen kehittymisestä huolimatta. Nuorten aikuisten sosiaalisessa hyvinvoinnissa esiintyi poikkeavuuksia lähinnä proliferatiivista diabeettista retinopatiaa sairastavilla. Tyypin 1 diabeteksen pitkälle edenneiden komplikaatioiden negatiivinen vaikutus jo nuorella aikuisiällä korostaa hyvän hoitotasapainon tärkeyttä yleisen elämänlaadun ylläpitämisessä.

En France, les programmes d’éducation thérapeutique du patient (ETP) à destination de l’adolescent diabétique de type 1 visent à rendre l’adolescent autonome pour gérer sa maladie et son traitement. En s’appuyant sur la théorie sociale cognitive de Bandura, les effets des activités éducatives de l’ETP devraient conduire au renforcement du sentiment d’efficacité personnelle, couplé à d’autres facteurs socio-cognitifs, favorisant l’adhésion thérapeutique de l’adolescent, une meilleure qualité de vie et un meilleur équilibre glycémique.Les travaux de thèse se sont déclinés en trois buts principaux :1) Réaliser une clarification de concept sur les spécificités de l’ETP dans un contexte pédiatrique, à partir d’une analyse de la littérature selon la méthode de Rogers (2000).2) Réaliser une revue systématique ayant pour objectif de décrire le contenu et les effets des programmes éducatifs de 2009 à 2014 sur le contrôle glycémique, la gestion de la maladie, les critères psychosociaux des enfants et des adolescents diabétiques de type 1, et d’évaluer la concordance de ces programmes avec les recommandations de l’ISPAD.3) Décrire l’évolution du profil socio-cognitif et clinique sur trois mois d’une cohorte d’adolescents diabétiques ayant participé à un programme d’ETP en France.Ces travaux ont permis de développer les connaissances sur le concept d’ETP dans le contexte pédiatrique, sur l’état de la recherche concernant les programmes éducatifs structurés dans le diabète de type 1 de l’enfant et de l’adolescent, mais aussi de mettre en application une étude pilote dans le contexte de l’ETP en France. / In France, therapeutic patient education programs (ETP) to adolescents with type 1 diabetes are designed to make the teenager to self-manage their disease and its treatment. Based on social cognitive theory of Bandura, the effects of educational activities should lead to the strengthening of self-efficacy, coupled with other socio-cognitive factors, favoring the therapeutic adherence of teenager, a better quality of life and improved glycemic control.The thesis work was broken down into three main goals:1) Perform concept clarification on the specificitiess of TpE in a pediatric context, from a literature analysis method according to Rogers (2000).2) To conduct a systematic review aimed to describe the content and effects of educational programs from 2009 to 2014 on glycemic control, disease management, psychosocial criteria of children and adolescents with type 1 diabetes, and assess the consistency of these programs with the recommendations of the ISPAD.3) Describe the evolution of the socio-cognitive and clinical profile on three months of a diabetic adolescent cohort participated in an ETP in France.This work helped to develop knowledge on the concept of TPE in the pediatric context, the state of research on structured educational programs in type 1 diabetes in children and adolescents, but also implement a pilot study in the context of the ETP in France

Diabetes Mellitus is a group of complex and heterogeneous metabolic disorders characterized by hyperglycemia. Even though the condition has been extensively studied, its causes and complex pathologies are still not fully understood. The occurring damage to the pancreatic islets is strikingly heterogeneous. In type 1 diabetes, the insulin producing beta cells are all destroyed within some islets, and similarly in type 2 diabetes, some islets may be severely affected by amyloid. At the same time other islets, in the near vicinity of the ones that are affected by disease, may appear fully normal in both diseases. Little is known about this heterogeneity in susceptibility to disease between pancreatic islets. This thesis examines the physiological and pathophysiological characteristics of islet subpopulations. Two subpopulations of islets were studied; one constituting highly vascularized islets with superior beta cell functionality, and one of low-oxygenated islets with low metabolic activity. The highly functional islets were found to be more susceptible to cellular stress both in vitro and in vivo, and developed more islet amyloid when metabolically challenged. Highly functional islets preferentially had a direct venous drainage, facilitating the distribution of islet hormones to the peripheral tissues. Further, these islets had an increased capacity for insulin secretion at low glucose levels, a response that was observed abolished in patients with recent onset type 1 diabetes.  The second investigated islet subpopulation, low-oxygenated islets, was found to be an over time stable subpopulation of islets with low vascular density and beta cell proliferation. In summary, two subpopulations of islets can be identified in the pancreas based on dissimilarities in vascular support and blood flow. These subpopulations appear to have different physiological functions of importance for the maintenance of glucose homeostasis. However, they also seem to differ in vulnerability, and a preferential death of the highly functional islets may accelerate the progression of both type 1 and type 2 diabetes.

Cette thèse s’intéresse au développement d’un contrôleur sûre et robuste en tant que partie intégrante d’un pancréas artificiel. Plus précisément, nous sommes intéressés à contrôler la partie du traitement usuel qui a pour but d’équilibrer la glycémie du patient. C’est ainsi que le développement d’une commande prédictive nonlinéaire robuste basée sur la résolution d’un problème de point selle a été envisagé. Afin de valider les performances du contrôleur dans une situation réaliste, des simulations numériques en utilisant une plate-forme de tests validée par la FDA sont envisagées.Dans une première partie, nous présentons une extension de la classique commande prédictive nonlinéaire dont le but est d’assurer le contrôle robuste de systèmes décrits par des équations différentielles ordinaires non linéaires dans un cadre échantillonné. Ce contrôleur, qui calcule une action de contrôle adéquate en considérant la solution d’un problème de point selle, est appelé saddle point model predictive controller (SPMPC). En utilisant cette commande, il est prouvé que le système converge en temps fini dans un espace borné et, en supposant une certaine structure dans le problème, qu’il est pratiquement stable entrée-état. Ensuite, nous nous sommes intéressés à la résolution numérique. Pour ce faire, nous proposons une méthode de résolution inspirée de la méthode du Langrangien augmenté et qui fait usage de modèles adjoints.Dans un deuxième temps, nous considérons l’application de ce contrôleur au problème du contrôle artificiel de la glycémie. Après une phase de modélisation, nous avons retenu deux modèles : un modèle simple qui est utilisé pour développer la commande et un modèle complexe qui est utilisé comme un simulateur réaliste de patients. Ce dernier est nécessaire pour valider notre approche de contrôle. Afin de calculer une entrée de commande adéquate, la commande SPMPC a besoin de l’état complet du système. Or, les capteurs ne peuvent fournir qu’une valeur du glucose sanguin. C’est pourquoi le développement d’un observateur est envisagé. Ensuite, des simulations sont réalisées. Les résultats obtenus témoignent de l’intérêt de l’approche retenue. En effet, pour tous les patients, aucune hypoglycémie n’a été observée et le temps passé en état hyperglycémique est suffisamment faible pour ne pas être dommageable. Enfin, l’intérêt d’étendre l’approche de commande SPMPC au problème de contrôle de systèmes décrits par des équations différentielles retardées non linéaires dans un cadre échantillonné est formellement investigué. / This thesis deals with the design of a robust and safe control algorithm to aim at an artificial pancreas. More precisely we will be interested in controlling the stabilizing part of a classical cure. To meet this objective, the design of a robust nonlinear model predictive controller based on the solution of a saddle point optimization problem is considered. Also, to test the controller performances in a realistic case, numerical simulations on a FDA validated testing platform are envisaged.In a first part, we present an extension of the usual nonlinear model predictive controller designed to robustly control, in a sampled-data framework, systems described by nonlinear ordinary differential equations. This controller, which computes the best control input by considering the solution of a constrained saddle point optimization problem, is called saddle point model predictive controller (SPMPC). Using this controller, it is proved that the closed-loop is Ultimately Bounded and, with some assumptions on the problem structure, Input-to State practically Stable. Then, we are interested in numerically solving the corresponding control problem. To do so, we propose an algorithm inspired from the augmented Lagrangian technique and which makes use of adjoint model.In a second part, we consider the application of this controller to the problem of artificial blood glucose control. After a modeling phase, two models are retained. A simple one will be used to design the controller and a complex one will be used to simulate realistic virtual patients. This latter is needed to validate our control approach. In order to compute a good control input, the SPMPC controller needs the full state value. However, the sensors can only provide the value of blood glucose. That is why the design of an adequate observer is envisaged. Then, numerical simulations are performed. The results show the interest of the approach. For all virtual patients, no hypoglycemia event occurs and the time spent in hyperglycemia is too short to induce damageable consequences. Finally, the interest of extending the SPMPC approach to consider the control of time delay systems in a sampled-data framework is numerically explored.

Adolescent athletes with type 1 diabetes (T1DM) face unique challenges when compared to peers with and without diabetes. Continuous subcutaneous insulin infusion (CSII) provides a method of insulin delivery that can enhance flexibility in insulin regimens and lifestyle that may be especially appealing to the adolescent athlete. No studies have explored the impact of athletics in this population. This descriptive qualitative study explored and described the experiences of adolescent athletes using CSII as their primary insulin delivery method, with a focus on athletic participation and performance. The purposeful sample consisted of four adolescent athletes, ages 13 to 15 years with T1DM, using CSII, in excellent diabetes control, and recently participated in organized sports activities. After written informed consent, data were collected through a semi-structured interview with the adolescent and parent. Results were transcribed verbatim and analyzed for emerging themes. Four themes emerged from the transcripts along with multiple subcategories. The main themes included: protecting the pump and infusion site; dealing with highs and lows; maximizing participation and performance; and keeping watch. Information gathered from this study will prepare healthcare professionals to anticipate the needs of adolescent athletes using CSII when prescribing a diabetes management regimen.

O transplante de ilhotas microencapsuladas constitui uma alternativa terapêutica interessante para o Diabetes Mellitus tipo 1, permitindo um melhor controle glicêmico e eliminando a necessidade de imunossupressão. Entretanto, a manutenção a longo prazo da viabilidade das células-&#946; ainda é um desafio. No isolamento, a perda da matriz extracelular e as condições hipóxicas subsequentes afetam decisivamente a sobrevivência e funcionalidade das ilhotas. Objetivo Para diminuir o estresse sobre o enxerto, levando a um sucesso prolongado do transplante, propôs-se a adição de perfluorocarbono (PFC) ou laminina (LN), moléculas associadas respectivamente à oxigenação e interações célula-célula, ao biomaterial baseado em alginato, Biodritina, adequado ao encapsulamento celular. Metodologia Para testar a estabilidade das formulações PFC-Biodritina e LN-Biodritina, microcápsulas foram submetidas a diferentes estresses (rotacional, osmótico, temperatura e cultura) por 7 e 30 dias. A pureza do biomaterial foi avaliada pela coincubação com macrófagos murinos RAW264.7, por 3, 9 e 24h, quando a ativação dos macrófagos foi observada pela expressão gênica de IL- 1&#946; e TNF&#945;. Microcápsulas implantadas i.p. em camundongos foram recuperadas após 7 ou 30 dias, para análises de biocompatibilidade. A expressão de níveis de mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulina 1 e 2), proteínas (Bax, Bcl-XL e Xiap) e a atividade de Caspase3 foram avaliadas em ilhotas microencapsuladas com PFC- e LN-Biodritina, após cultura de 48h em condições de normóxia e hipóxia (<2% O2). Camundongos diabéticos foram transplantados com ilhotas encapsuladas nas diferentes formulações e os animais foram monitorados pelas variações de massa corporal, glicêmicas e pela funcionalidade do enxerto (TOTGs). As ilhotas foram recuperadas de animais normo ou hiperglicêmicos e uma análise de biocompatibilidade das cápsulas foi realizada, assim como a avaliação funcional das células-&#946;. Após o explante, a glicemia dos animais normoglicêmicos foi monitorada para se atestar a eficiência das ilhotas transplantadas. Resultados Microcápsulas de PFC- e LN-Biodritina são tão estáveis e biocompatíveis quanto as de Biodritina. Para ilhotas encapsuladas em ambos os materiais, em normóxia ou hipóxia, observou-se uma modulação gênica que sugere proteção contra apoptose. Adicionalmente, encontrou-se uma diminuição na expressão de genes indicadores de estresse (mcp1, hsp70). Uma diminuição nos níveis de mRNA de ldh foi vista para PFC-Biodritina, mas o oposto foi encontrado para LN-Biodritina. As diferenças encontradas na expressão proteica sugerem o mesmo padrão anti-apoptótico. Caspase3 não foi modulada por nenhum biomaterial. Nos experimentos de transplante, apenas LN-Biodritina levou reversão prolongada do diabetes, com 60% dos animais normoglicêmicos, 198 dias pós-cirurgia, comparado a 9% do grupo Biodritina. O TOTG demonstrou que camundongos transplantados com ilhotas encapsuladas secretaram mais insulina do que controles, 60 (LN-Biodritina) ou 100 (PFC- e LN-Biodritina) dias pós-cirurgia. O explante restabeleceu a hiperglicemia nos camundongos. Microcápsulas recuperadas de animais hiperglicêmicos apresentavam uma extensa adesão celular. Testes de secreção de insulina in vitro demonstraram que somente ilhotas do grupo normoglicêmico responderam às variações da concentração de glicose. Conclusão A adição de moléculas bioativas à Biodritina é capaz de diminuir o estresse em ilhotas isoladas e tem o potencial de melhorar a terapia pelo transplante de ilhotas. / Transplantation of microencapsulated islets represents an attractive therapeutical approach to treat type 1 Diabetes Mellitus, accounting for an improved glycemic control and the abolishment of immunosuppressive therapies. However, maintenance of long-term &#946;-cell viability remains a major problem. During islet isolation, the loss of extracellular matrix interactions and the hypoxic conditions thereafter dramatically affect &#946;-cell survival and function. Objective To lessen the burden of islet stress and achieve a better outcome in islet transplantation we tested the addition of perfluorocarbon (PFC) or laminin (LN), molecules associated respectively with oxygenation and cell-cell interaction, to Biodritin, an alginate-based material suitable for cell microencapsulation. Methodology To test the stability of PFC-Biodritin and LN-Biodritin composites, microcapsules were subjected to different stresses (rotational, osmotic, temperature and culture) for 7 and 30 days. To assess biomaterial purity microcapsules were co-incubated with RAW264.7 murine macrophage cell line for 3, 9 and 24h and macrophage activation was detected through mRNA levels of IL-1&#946; and TNF&#945;. Microcapsules were implanted i.p. in mice and retrieved after 7 or 30 days, for biocompatibility analyses. Gene expression at mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulin 1 and 2) and protein (Bax, Bcl-XL and Xiap) levels, together with Caspase3 activity, were evaluated in islets microencapsulated in PFC- or LN-Biodritin, upon culturing for 48h in normoxic or hypoxic (<2% O2) conditions. Diabetic mice were transplanted with PFC- or LN-Biodritin microencapsulated islets, followed by assessments of body weight, glycemia and graft function by oral glucose tolerance tests (OGTTs). Microencapsulated islets were retrieved from normoglycemic or hyperglycemic mice and biocompatibility analyses of the beads together with a functional assessment of the graft followed. After graft removal, normoglycemic animals had their glycemias monitored to attest the efficacy of the transplanted islets. Results PFC- and LN-Biodritin microcapsules were as stable and biocompatible as Biodritin. For both biomaterials in normoxia and hypoxia a modulation in gene expression was observed in islets associated with a protection against apoptosis. Also, a decreased expression of stress-related genes (mcp1, hsp70) was evidenced. ldh mRNA levels were down-regulated in PFC-Biodritin microencapsulated islets but upregulated in the presence of LN. Increased levels of insulin mRNA were observed. The differences seen in protein expression indicated the same anti-apoptotic pattern. Caspase3 activity was not different between groups. Concerning diabetes reversal experiments, only mice transplanted with LN-Biodritin microencapsulated islets presented a better outcome, with 60% remaining euglycemic at 198 days post-surgery, compared with 9% for the Biodritin group. OGTT showed that mice transplanted with encapsulated islets secreted more insulin than normal mice, 60 (LN-Biodritin) or 100 days (PFC- and LN-Biodritina) posttransplant. Hyperglycemia was achieved after the retrieval of microcapsules showing graft efficacy. Retrieved microcapsules revealed an extensive overgrowth in most beads from hyperglycemic mice. A static glucose stimulated insulin secretion test revealed that only islets from normoglycemic subjects were able to secrete insulin according to glucose concentration. Conclusion- The addition of bioactive molecules to Biodritin may lessen the stress of isolated islets and have the potential to improve islet transplantation therapy.

Type 1 diabetes is an autoimmune disease leading to insulin deficiency. Autoantibodies to beta cell proteins are already present in the asymptomatic phase of type 1 diabetes. Recent findings have suggested a number of additional minor autoantigens in patients with type 1 diabetes. We have established luciferase immunoprecipitation systems (LIPS) for anti-MTIF3, anti-PPIL2, anti-NUP50 and anti-MLH1 and analyzed samples from 500 patients with type 1 diabetes at onset of clinical disease and 200 healthy individuals who had a family history of type 1 diabetes but no evidence of beta cell autoantibodies. We show significantly higher frequencies of anti-MTIF3, anti-PPIL2 and anti-MLH1 in recent onset type 1 diabetes patients in comparison to controls. In addition, antibodies to NUP50 were associated with HLA-DRB1*03 and antibodies to MLH1 were associated with HLA-DRB1*04 genotypes.:1. Introduction 2. Material and methods 2.1 Participants 2.2. Cloning and expression of antigens 2.3. Luciferase ImmunoPrecipitation (LIPS) assays 2.4. Antinuclear antibodies (ANA) 2.5. Statistics 3. Results 4. Discussion 5. Conclusion Declaration of interest Funding Acknowledgements Appendix A Suplementary data References

Bakgrund: Fysisk aktivitet är en del av egenvården för individer med diabetes mellitus typ 1. Upprätthålla en god glykemisk balans samt att inte drabbas av hypoglykemi beskrivs vara en svårighet. Syfte: Syftet var att belysa faktorer som påverkar individer med diabetes mellitus typ 1 att utföra fysisk aktivitet som en del av egenvården. Metod: Studien genomfördes genom en allmän litteraturöversikt med induktiv ansats. Resultatet baserades på nio vetenskapliga artiklar. Resultat: Tre kategorier framkom: Kunskapsläget hos sjuksköterskan och individen, Förmåga att använda strategier samt Förekomsten av stöd till individer. Individer upplevde en rädsla för att drabbas av hypoglykemi vid fysisk aktivitet, och denna rädsla var starkt kopplad till de olika faktorerna kunskap, strategier och stöd. Dock upplevdes sjuksköterskans stöd bristfälligt. Konklusion: Litteraturstudien påvisade att det fanns faktorer som påverkade individens utförande av fysisk aktivitet. Vidare forskning om faktorer som kan underlätta fysisk aktivitet för individer med diabetes mellitus typ 1 är nödvändigt. Eftersom sjuksköterskan i undervisningen om egenvård ska kunna bidra med större kunskap, ett bättre stöd och bättre strategier för hanteringen av individens egenvård vid fysisk aktivitet. / Background: Physical activity is a part of self-care for individuals with diabetes mellitus type 1. To not suffer from hypoglycemia and to maintain a good glycemic balance is described to be of difficulty. Aim: The aim was to highlight the factors that affect individuals with diabetes mellitus type 1 to execute physical activity as a part of their self-care. Method: The study was carried out through a literature review with inductive approach. The result was based on nine papers. Result: Three categories emerged: Knowledge, Strategies and Emotional support. Individuals experienced a fear of hypoglycemia while doing physical activities. This fear was strongly related to different factors and the nurse’s support was perceived as inadequate. Conclusion: The literary study showed the factors that affected the individual's execution for physical activity. Further research about factors that can facilitate physical activity for individuals with Diabetes mellitus type 1 is necessary. This should be implemented in the nurse’s instruction to the individual to give a wider knowledge. Also, to give a better emotional support thus contributing to better strategies in handling the individual’s self-care with physical activity.

Bakgrund: Diabetes typ 1 är en kronisk autoimmun sjukdom som kännetecknas av insulinbrist. Förekomsten av diabeteskomplikationer under barndomen är låg men unga vuxna har en högre risk att utveckla komplikationer samt bristfällig diabetes hantering under olika utvecklingsfaser. Unga vuxna befinner sig i en utmanande tid och att leva med Diabetes typ 1 är en faktor som ökar bördan till de redan befintliga stressfaktorerna. Personcentrerad vård främjar unga vuxnas egenförmåga att självständigt hantera sin diabetes. Syfte: Studiens syfte var att beskriva unga vuxnas erfarenheter att leva med Diabetes typ 1. Metod: Metoden som användes för att besvara studiens syfte var litteraturöversikt. Databaserna som användes vid datainsamlingen var PubMed samt CINAHL. Artiklarna var publicerade mellan år 2011–2021. Unga vuxna definierades utifrån åldern 15–40 år. Integrerad analysmetod användes för att analysera och sammanställa resultatet. Resultat: Resultatet är baserat på 15 vetenskapliga artiklar och presenteras med två huvudkategorier samt fyra underkategorier. Resultatet belyser både upplevelsen av sociala sammanhang samt hur unga vuxna upplever att det är att leva med diabetes typ 1. Områden som resultatet djupare går in på är skolgång, arbetsliv, kontakt med vården, förändringar och motgångar och påverkan av tidigare erfarenheter. Slutsats: Studien visar att unga vuxna påverkas på flera sätt av diagnosen DM1. Skolgång och arbetsliv påverkas och den unga vuxna kan känna sig annorlunda och utanför i samhället. Genom att hitta gemenskap med andra unga med DM1 samt bra stöd från hälso- och sjukvård samt anhöriga upplever den unga vuxna att hanteringen av sin diabetes typ 1 underlättas. / Background: Type 1 diabetes is a chronic autoimmune disease characterized by insulin deficiency. The incidence of diabetic complications during childhood is low, but young adults have a higher risk of developing complications and inadequate diabetes management during different developmental stages. Young adults are in a challenging time and living with Type 1 diabetes is a factor increasing the burden of the already existing stressors. Person-centered care promotes young adults to manage their diabetes independently. Purpose: The purpose of the study was to describe young adults' experiences of living with type 1 diabetes. Method: The method used to answer the purpose of the study was a literature review. The databases used were PubMed and CINAHL for data collection. Articles were published between year 2011-2021. Young adults were defined as 15-40 years old. Integrated analysis method was used to analyze and compile the results. Result: The result is based on 15 scientific articles and is presented with two main categories and four subcategories. The results shed light on both the experience of social contexts and how young adults experience what it is like to live with type 1 diabetes. Areas that the results go into more deeply are schooling, working life, contact with care, changes and setbacks and the impact of earlier experience. Conclusion: The study shows that young adults are affected in several ways by their Type 1 diabetes. Schooling and working life are affected and the young adult may feel different and outside of society. By finding fellowship with other young people with DM1 and good support from health and medical care and relatives, the young adult experiences that the management of their DM1 is facilitated.