Type 1 diabetes (T1D) is etiologically considered as an autoimmune disease, where insulin-producing β-cells are damaged by autoimmune attacks. Regulatory T (Treg) cells are immune homeostasis cells. In the present thesis I aimed to investigate the role of Treg cells and other immune cells in the early development of T1D. In order to do that, we first determined which immune cells that are altered at an early stage of the T1D development. We found that dendritic cells and plasmacytoid dendritic cells induce the initial immune response. Next, we investigated the role of Treg cells in multiple low dose streptozotocin (MLDSTZ) induced T1D and in NOD mice. We found that the numbers of Treg cells were increased in both MLDSTZ and NOD mice when the MLDSTZ mice were hyperglycemic. However, the increased Treg cells showed a decreased production of anti-inflammatory cytokines (IL-10, IL-35 and TGF-β) and an increased expression of pro-inflammatory cytokines (IFN-γ and IL-17a). These results revealed that Treg cells switch their phenotype under T1D conditions. IL-35 administration effectively prevented the development of, and reversed established MLDSTZ induced T1D. Treg cells from IL-35 treated mice showed an increased expression of the Eos transcription factor, accompanied by an increased expression of IL-35 and a decreased expression of IFN-γ and IL-17a. These data indicate that IL-35 administration counteracted the early development of T1D by maintaining the phenotype of the Treg cells. Furthermore, IL-35 administration reversed established T1D in the NOD mouse model by maintaining the phenotype of Treg cells, seemingly by inducing the expression of Eos. Moreover, the circulating level of IL-35 was significantly lowered in both new onset and long-standing T1D patients compared to healthy controls. In addition, patients with T1D with remaining C-peptide had significantly higher levels of IL-35 than patients lacking C-peptide, suggesting that IL-35 might prevent the loss of β-cell mass. In line with this hypothesis, we found that LADA patients had a higher proportion of IL-35+ tolerogenic antigen presenting cells than T1D patients. Subsequently, we determined the proportions of IL-35+ Treg cells and IL-17a+ Treg cells in T1D patients with diabetic nephropathy (DN), which were age, sex and BMI matched with healthy controls and T1D patients. The proportion of IL-35+ Treg cells was decreased in DN and T1D patients, but IL-17a+ Treg cells were more abundant than in healthy controls. Furthermore, we found that the number of Foxp3+ Treg cells was increased in the kidneys of MLDSTZ mice. However, infiltration of mononuclear cells was seen in kidneys of these mice. In addition, kidney tissues of IL-35 treated MLDSTZ mice did not show any mononuclear cell infiltration. These results demonstrate that IL-35 may be used to prevent mononuclear cell infiltration in kidney diseases. Our findings indicate that the numbers of Foxp3+ Treg cells are increased in T1D, but that these Treg cells fail to counteract the ongoing immune assault in islets and kidneys of hyperglycemic mice. This could be explained by a phenotypic shift of the Treg cells under hyperglycemic conditions. IL-35 administration reversed established T1D in two different animal models of T1D and prevented mononuclear cell infiltration in the kidneys by maintaining the phenotype of Treg cells.

L'interleukine-2 (IL-2) est nécessaire à l'homéostasie des lymphocytes T régulateurs CD4+ Foxp3+ (Tregs) et son administration à faibles doses permet d'induire une expansion spécifique et dose-dépendante de ces cellules. Nous avons précédemment démontré que l'administration d'IL-2 à faibles doses permet de restaurer la tolérance immunitaire chez la souris NOD (modèle murin de diabète autoimmun). Toutefois cette stratégie n'est efficace à long terme que chez 30% des souris traitées.Mon travail de thèse a porte? sur l'amélioration de la thérapie par faibles doses d'IL-2. Dans un premier temps, nous avons démontré que la combinaison de l'IL-2 avec la rapamycine, une drogue ciblant préférentiellement les lymphocytes T effecteurs et épargnant les Tregs, ne permet pas d'améliorer le traitement. Au contraire, la rapamycine abolit de façon transitoire la tolérance induite par l'IL-2. Dans un deuxième temps, nous avons essayé d'augmenter les doses d'IL-2, dans le but d'induire une activation plus forte des Tregs. Néanmoins, le traitement par fortes doses d'IL-2 ne prévient pas le diabète autoimmun mais accélère son développement et est associé à une très forte toxicité.Ensuite, un deuxième axe de ma thèse s'est articulé autour de notre découverte de l'existence d'autoanticorps anti-IL-2 neutralisants chez la souris NOD et les patients souffrant de diabète de type 1. Ces autoanticorps modulent négativement l'homéostasie des Tregs in vivo, suggérant un rôle potentiel dans la physiopathologie du diabète autoimmun.Dans l'ensemble, ces résultats permettent de reconsidérer l'utilisation de l'IL-2 à faibles doses, seule ou combinée, dans le contexte du diabète de type 1. / CD4+ Foxp3+ regulatory T cells (Treg cells) are essential for the maintenance of immune tolerance. Interleukin-2 (IL-2) is mandatory for the homeostasis of Treg cells and its administration at low-doses induces a specific dose-dependent boost of Treg cells. Previous work has demonstrated that a short-tem treatment with low-doses IL-2 can revert established autoimmune diabetes in the NOD mouse model. However, this strategy induces long-term reversal in only 30% of the treated mice and can be optimized. During my PHD, my work has focused on the optimization of T1D therapy with low-doses of IL-2. First, we tried to combine low-doses of IL-2 with rapamycin, an immunosuppressive drug known to mainly affect Teff cells. The combined treatment (IL-2/Rapa) did not induce diabetes reversal and even reversibly broke IL-2-induced tolerance. Then, we tried to increase the IL-2 dose in order to increase the amplitude of the Treg boost. However, despite an important Treg cell boost, high-doses IL-2 administration to pre-diabetic NOD mice was toxic and precipitated T1D onset. In a second project, we described the existence of neutralizing anti-IL-2 autoantibodies in NOD mice and T1D patients. Our data suggested that anti-IL-2 autoantibodies negatively impacted on Treg cell homeostasis in vivo, contributing to the impaired immune tolerance observed in NOD mice and T1D patients. Altogether, our results lead to the consideration of low-doses IL-2, alone or combined, for the treatment of T1D. In addition, our demonstration of the existence of anti-IL-2 autoantibodies in NOD mice and T1D patients leads to a better understanding of T1D physiopathology.

La régulation de la concentration de glucose dans l'organisme est nécessaire au bon fonctionnement des globules rouges et de l'ensemble des cellules, dont celles des muscles et du cerveau. Cette régulation met en jeu plusieurs organes ainsi que le système hormonal dont une hormone en particulier, l’insuline. Le diabète de type 1 est une maladie où les cellules productrices d'insuline du pancréas sont détruites. Afin de compenser cette perte de production d'insuline, le traitement de cette maladie consiste, pour le patient, à déterminer une dose d'insuline à s'injecter en fonction de mesures de sa glycémie et de certaines caractéristiques intervenant dans la régulation de celle-ci (repas, activité physique, stress,...). Cette thèse s'inscrit dans une démarche d’automatisation du traitement en proposant un nouveau modèle non-linéaire du métabolisme glucidique pouvant être utilisé dans une solution de contrôle en boucle fermée. Nous avons prouvé que ce modèle possède une unique solution positive et bornée pour des conditions initiales fixées et sa commandabilité locale. Nous nous sommes ensuite intéressés à l’identification paramétrique de ce modèle. Nous avons montré son identifiabilité structurelle et pratique. Dans ce cadre, une nouvelle méthodologie permettant de qualifier l'identifiabilité pratique d'un modèle, basée sur une divergence de Kullback-Leibler, a été proposée. Une estimation des paramètres du modèle a été réalisée à partir de données de patients réels. Dans ce but, une méthodologie d'estimation robuste, basée sur un critère de Huber, a été utilisée. Les résultats obtenus ont montré la pertinence du nouveau modèle proposé. / The development of new control models to represent more accurately the plasma glucose-insulin dynamics in T1DM is needed for efficient closed-loop algorithms. In this PhD thesis, we proposed a new nonlinear model of five time-continuous state equations with the aim to identify its parameters from easily available real patients' data (i.e. data from the insulin pump and the glucose monitoring system. Its design is based on two assumptions. Firstly, two successive remote compartments, one for insulin and one for glucose issued from the meal, are introduced to account for the distribution of the insulin and the glucose in the organism. Secondly, the insulin action in glucose disappearance is modeled through an original nonlinear form. The mathematical properties of this model have been studied and we proved that a unique, positive and bounded solution exists for a fixed initial condition. It is also shown that the model is locally accessible. In this way, it can so be used as a control model. We proved the structural identifiability of this model and proposed a new method based on the Kullback-Leiber divergence in view to test its practical identifiability. The parameters of the model were estimated from real patients' data. The obtained mean fit indicates a good approximation of the glucose metabolism of real patients. The predictions of the model approximate accurately the glycemia of the studied patients during few hours. Finally, the obtained results let us validate the relevance of this new model as a control model in view to be applied to closed-loop algorithms.

Purpose: To describe family perceptions about pediatric primary care management following diagnosis of type 1 diabetes mellitus (T1DM) in preschool-aged children living in the Pacific Northwest region of the United States. Study Design and Method: Mothers of children diagnosed with T1DM before the fifth birthday and within the past two years were recruited anonymously through two regional support groups. Perceptions about pediatric primary care management following T1DM diagnosis were elicited through an anonymous 30-item online survey. Demographic characteristics of mother and child were obtained as well as information about five important domains of health care management for a young child with T1DM: (1) multidisciplinary, (2) holistic and compassionate, (3) accessible and communicative, (4) uses current standards and technology, and (5) actively promotes safe self-management. Results: Twenty-one biological mothers participated in this study, each on behalf of a child diagnosed with T1DM who fit inclusion criteria. Overall mothers held positive perceptions about care management by PCPs and endocrinologists within context of each of the five domains. Most mothers felt included in care planning, valued periodic well-child exams, and believed the child's providers were accessible, communicated effectively, and usually demonstrated consideration/compassion for the family. Although a majority of mothers at least somewhat agreed that the PCP used current standards and technology to care for the child, and functioned as the center of his/her health care coordination, these domains elicited a slightly greater number of responses indicating uncertainty or disagreement. Clinical Implications: Nurses and pediatric practitioners can use findings from this study to plan continued exploration into the perceptions and care management needs of families following diagnosis of a very young child with T1DM. The domains of care used to assess mothers' perceptions about care management-based on tenets of the Chronic Care Model (CCM) and Patient Centered Medical Home (PCMH)-can be used by pediatric PCPs and endocrinologists to dialogue with patients and staff about how care management may be improved for these families. Providing opportunities for feedback to the families of young children with T1DM should be encouraged so future research can examine relationships between care management variables and clinical outcomes.

Introdução: O controle glicêmico estrito com múltiplas injeções diárias de insulina é o foco do tratamento para diabetes mellitus tipo 1 (DM1), mas geralmente está associado a um aumento no número de episódios de hipoglicemia, e o estresse de conviver com esse evento pode estar associado a prejuízos para a saúde mental do paciente. Embora os análogos de insulina de ação prolongada tenham propriedades farmacológicas para imitar o perfil fisiológico de insulina, a literatura não é unânime em demonstrar esse efeito em comparação à insulina humana. No Brasil, apenas alguns estados, incluindo o Rio Grande do Sul (RS), fornecem análogos de insulina para pacientes com DM1. O objetivo deste estudo foi avaliar a frequência de hipoglicemias e a satisfação dos pacientes com DM1 que recebem análogos de insulina de curta e longa ação após sua introdução no Rio Grande do Sul (RS). Materiais e métodos: Estudo transversal, retrospectivo, realizado com pacientes adultos com diabetes tipo 1, residentes de 38 cidades do estado do Rio Grande do Sul, que recebiam análogos de insulina via Secretaria Estadual de Saúde. Os dados clínicos e demográficos foram avaliados por formulário auto-respondido, a satisfação dos pacientes com o tratamento através do Questionário de satisfação com o tratamento do diabetes (DTSQs) e os transtornos mentais comuns (TMC) através do Questionário sobre saúde geral (QSG-12). Resultados: Um total de 507 pacientes foram incluídos, com idade média de 38,6±13,7 anos, 52% feminino, com duração do DM 18 [IQR25-75 = 11-25] anos e 36,8% com ensino superior completo. A pontuação mediana de satisfação com o tratamento (DTSQs) foi de 32 [IQR25-75 = 29 -35]. A satisfação dos pacientes não reduziu a longo prazo. A taxa de pacientes com hipoglicemias, incluindo grave e noturna, não alterou com o tempo de uso dos análogos de insulina. Apesar de taxas altas de hipoglicemias e com a maioria dos pacientes com triagem positiva para transtornos mentais comuns os pacientes mantiveram altos escores de satisfação com o tratamento, o que não reduziu em longo prazo como em outras intervenções em doenças crônicas. / Introduction: Strict glycemic control with multiple daily insulin injections is the focus of treatment for type 1 diabetes (T1D), but it is usually associated with an increase in the number of hypoglycemia episodes, and the stress of living with this event may be associated with damages to the mental health of the patient. Although long-acting insulin analogues have pharmacological properties to mimic physiologic insulin profile, literature is not unanimous in showing this effect in comparison to human insulin. In Brazil, only some states, including Rio Grande do Sul (RS), provide insulin analogues for T1D patients. The purpose of this study was to evaluate the frequency of hypoglycemia and the satisfaction of T1D patients who receive short and long acting insulin analogues after their introduction in RS. Methods: A cross-sectional, retrospective study was conducted with adult patients with T1D, residents of 38 cities in Rio Grande do Sul state, who received insulin analogues via the State Department of Health. Demographic and clinical data was evaluated through a self-responded questionnaire; satisfaction, analyzed using the Diabetes Treatment Satisfaction Questionnaire (DTSQs), and Common Mental Disorders (CMD), analyzed using the General Health Questionnaire (QSG-12). Results: A total of 507 T1D patients were included, with a mean age of 38.6 ± 13.7 years, 52% female, with diabetes duration of 18 (11-25) years and 36.8% with complete higher education. The medium score of satisfaction with the treatment (DTSQs) was 32 [IQR25-75 = 29 -35]. Patient satisfaction was not reduced in the long term. The rate of patients with hypoglycemia, including severe and nocturnal hypoglycemia, was not changed with the time use insulin analogues. Although high rates of hypoglycaemia and with most patients with positive 14 screening for common mental disorders patients maintained high satisfaction scores with treatment, which did not reduce in the long term as in other interventions in chronic diseases.

Introduction : L'augmentation de l'incidence mondiale du diabète de type 1 (DT1) a été calculée à 3,0% par année en moyenne et il a été prédit qu'elle serait de 40% en 2010 chez les enfants âgés de 0 à 14 ans. Les causes de cette augmentation ne sont pas encore déterminées; cette thèse met à jour les connaissances actuelles sur l'incidence mondiale du DT1, en profitant de la disponibilité croissante des bases de données publiques et en examinant la corrélation entre l'incidence et les caractéristiques des pays. Méthodes : Une recherche exhaustive et systématique des articles publiés sur l'incidence du DT1 dans le monde a été effectuée pour étudier les variations globales de cette incidence dans les divers pays. L'objectif initial de cette thèse était d'étudier la corrélation entre les variables environnementales disponibles dans les bases de données publiques, et l'incidence du DT1 selon les pays.Conclusions et implications : Au cours de cette thèse, nous avons quantifié la variation pays par pays de l'incidence du DT1 dans le monde chez les enfants et les adultes, montrons qu'une grande partie de cette incidence pourrait s’expliquer par la variabilité de facteurs environnementaux d’un pays à l’autre. Cette thèse a également profité de la disponibilité croissante de données publiques sur la variation des facteurs environnementaux et génétiques de pays à pays, qui peuvent être impliqués dans le fort effet de cohorte de naissance qui a été observé ; il est conseillé d'approfondir la recherche sur la grossesse et la période néonatale et son implication dans DT1. / Background: The increase of worldwide incidence of type 1 diabetes (T1D) was calculated to be on average 3.0% per year and it was predicted that it would be 40% higher in 2010 in children aged 0-14 years. The causes of this increase are still under study; this thesis updates our current knowledge on the global incidence of T1D, and taking advantage of the increasing availability of public databases examines the correlation between incidence and country characteristics. Methods: A comprehensive systematic literature search of published articles on the incidence of T1D worldwide was conducted to study global variations of the incidence within countries. The initial goal of this thesis was to study the correlation between environmental variables available in public databases with the country incidence of T1D. Conclusions and implications: During this thesis, we quantified the country-to-country variation in T1D incidence worldwide in children and adults, and show that a large part of this incidence could be accounted for by the variability of environmental factors within the countries taking advantage of the increasing availability of public databases. Environmental factors may be involved in the strong cohort effect we found; it is advisable to deepen the research on pregnancy and neonatal period and its implications on T1D. Here we could quantify that the increase of T1D was even larger than had been predicted in an earlier study.

O diabetes mellitus do tipo 1 (DM1) é uma doença autoimune que se desenvolve a partir da ação combinada de múltiplos fatores genéticos e ambientais, sendo caracterizada pela perda seletiva das células produtoras de insulina nas ilhotas pancreáticas em indivíduos geneticamente susceptíveis. O HLA de classe II, localizado no cromossomo humano 6p21.3, representa uma das regiões genômicas mais importantes associadas ao DM1, embora evidências apontem para a participação de diversos outros loci na susceptibilidade à doença. Essas regiões cromossômicas poderiam apresentar genes funcionalmente ativos com perfis transcricionais semelhantes ao camundongo Mus musculus, muito utilizado como modelo animal para o estudo de doenças humanas. Para testar esta hipótese, foi realizada análise dos perfis transcricionais de linfócitos periféricos provenientes de pacientes com DM1 e camundongos NOD (Non-obese diabetic) diabéticos, focando os genes situados em regiões de susceptibilidade. Foram utilizados dados de microarrays do genoma funcional completo da plataforma Agilent (Whole genome one-color Agilent 4x44k) de dezenove pacientes e oito controles, e de camundongos NOD pré-diabéticos e diabéticos. A linhagem NOD foi utilizada no estudo, pois representa um modelo experimental para o estudo do diabetes autoimune e desenvolve a doença espontaneamente. Para a análise dos dados de microarrays foi utilizado o software GeneSpring GX e os programas Cluster e TreeView. A modulação transcricional dos genes foi estabelecida comparando-se os pacientes com os controles, e os animais diabéticos com os pré-diabéticos. Os loci de susceptibilidade ao DM1 humano foram definidos utilizando-se uma tabela curada disponível no banco T1DBase (http://t1dbase.org) e seus correspondentes murinos, segundo o banco de dados Homology Maps (http://www.ncbi.nlm.nih.gov/projects/homology/maps/). Foram considerados para o estudo apenas os pares de homólogos com expressão em linfócitos humanos e murinos conforme os dados disponíveis no banco BioGPS (http://biogps.org). Avaliamos se os genes murinos estavam situados em regiões de susceptibilidade (Idd) ao DM1 do camundongo, utilizando-se o T1DBase. Todos os genes humanos selecionados com homologia com camundongo foram mapeados quanto à localização cromossômica, buscando-se por regiões de sintenia entre as duas espécies por meio da ferramenta Synteny disponível no banco de dados Ensembl Genome Browser (http://www. ensembl.org/). Os pares de homólogos situados em regiões sintênicas foram então verificados quanto à similaridade de sequência de DNA e identidade protéica entre humano e camundongo, utilizando-se dados do HomoloGene (http://www.ncbi.nlm.nih. gov/homologene/). Foram analisados 463 genes humanos, dos quais 73 apresentaram correspondência em camundongo e expressão em linfócitos T. Dos 73 genes identificados, 31 deles apresentaram mesma modulação de fold change entre as duas espécies, com 12 mapeados em regiões de susceptibilidade murinas (Idd). Dos doze genes em regiões Idd, 4 se apresentaram induzidos: APOM (Apom), COL11A2 (Col11a2), HLA-DOB (H2-Ob) e PRR3 (Prr3); e 8 reprimidos: CYP21A2 (Cyp21a1), STK19 (Stk19), PHTF1 (Phtf1), RSBN1 (Rsbn1), CDSN (Cdsn), TRIM39 (Trim39), VARS2 (Vars2) e IL21 (Il21). Foram identificados 59 genes em regiões de sintenia humano-camundongo, com 58 apresentando similaridade na sequência de DNA acima de 70% entre as duas espécies, e identidade de sequência de aminoácidos das respectivas proteínas variando de 61,4 a 99,7%. Esses resultados demonstram que a maioria dos genes estudados apresenta conservação funcional, como indicado pelo alto grau de identidade das proteínas. Além disso, evidenciou-se um compartilhamento de perfis de expressão de genes em regiões de susceptibilidade ao DM1 humano e murino, contribuindo para um melhor conhecimento das semelhanças entre o modelo animal (linhagem NOD) e o diabetes autoimune humano. / Type 1 diabetes (T1D) is a common autoimmune disease that arises from multiple genetic and environmental risk factors. It is characterized by selective loss of insulin-producing -cells in the pancreatic islets in genetically susceptible individuals. The HLA class II locus on human chromosome 6p21.3 represents one of the most important genomic regions associated with T1D but there are evidences for the participation of several others along the chromosomes, which also contribute to disease susceptibility. These chromosomal regions may harbor functional genes with transcriptional profiles similar to those presented by the mouse Mus musculus, an animal model highly used in researches of human diseases. To test this hypothesis, it was performed a transcriptome profiling analysis of peripheral lymphocytes from T1D patients and diabetic NOD (Non-obese diabetic) mice focusing those genes positioned in chromosomal susceptibility regions. To perform this analysis, whole genome one-color Agilent 4x44k microarrays were used from 19 patients and 8 controls and from pre-diabetic and diabetic NOD mice. NOD strain was used since It is a well established mouse model for T1D. GeneSpring GX software and Cluster and TreeView programs were applied for microarray data analysis. The transcriptional modulation was established by comparisons of diabetic patients versus controls and diabetic versus pre-diabetic animals. The human T1D susceptibility loci were defined using a curated human dataset available in T1DBase (http://t1dbase.org) and mouse counterparts according to Homology Maps database (http://www.ncbi.nlm.nih.gov/projects/homology/maps/). For the present study we considered only homolog gene pairs with expression in human and mouse lymphocytes taking into account data available in BioGPS database (http://biogps.org). Following these procedures, mouse genes were checked for chromosome location in order to subserve the establishment of syntenic regions. The human-mouse syntenic regions were defined using Synteny tool from Ensembl Genome Browser (http://www.ensembl.org/). The homolog gene pairs located in human-mouse syntenic regions were checked for DNA sequence similarity and protein identity according to HomoloGene data (http://www.ncbi.nlm.nih.gov/homologene/). The 463 human genes were analyzed with 73 presenting murine counterparts and expression in lymphocytes. From these, 31 genes presented same fold change modulation in both species, with 12 of them mapped in murine diabetes susceptibility regions (Idd). The 12 genes in Idd regions showed different transcriptional modulations, 4 featured up-regulation: APOM (Apom), COL11A2 (Col11a2), HLA-DOB (H2- Ob) e PRR3 (Prr3); and 8 down-regulation: CYP21A2 (Cyp21a1), STK19 (Stk19), PHTF1 (Phtf1), RSBN1 (Rsbn1), CDSN (Cdsn), TRIM39 (Trim39), VARS2 (Vars2) e IL21 (Il21). 51 genes were identified in human-mouse syntenic regions with 58 presenting DNA sequence similarity above 70% and protein identity ranging from 61,4 to 99,7%. These results show that most genes studied present functional conservation, as indicated by the high degree of identity of the proteins. Additionally, it was observed shared expression profiles between human and murine T1D susceptibility regions. These results contribute to a better understanding of similarities between the animal model (NOD mouse strain) and human autoimmune diabetes.

Bakgrund: Typ 1-diabetes en av de vanligaste, svåra kroniska sjukdomarna bland barn och ca 8000 barn i Sverige är drabbade. Vid insjuknande får barnen kontakt med tvärprofessionella diabetesteam, en kontakt de behåller till 18 årsdagen. Det finns flera fördelar med teamarbete och de tvärprofessionella teamen uppskattas av både personal, patienter och anhöriga. Teamets kompetens och sammansättning har en stor betydelse kring vården för familjerna. Motiv: Målet är att bidra med en ökad förståelse av det stöd tvärprofessionella team kan bidra med samt eventuellt finna förslag på utvecklings- och förbättringsarbete inom diabetesvården. Syfte: Syftet med studien är att belysa föräldrars upplevelse av stöd från tvärprofessionella diabetesteam. Metod: En kvalitativ intervjustudie. Resultat: Föräldrarnas erfarenheter av diabetesteamets stöd genomsyrades av positivitet, men visade även en viss brist på föräldrastöd. Intervjuernas resultat mynnade ut i 3 huvudkategorier; ”Stödjande relation”, ”Stöd i lidande” och ”Stöd i vardagen”. Konklusion: För att möta upp föräldrarnas behov av stöd krävs en förändring kring diabetesteamens arbete. En mer individanpassadomvårdad, där även föräldrars psykosociala behov inkluderas vilket gynnar hela familjen. / Background: Type 1-diabetes is one of the most common, severe chronic diseases among children and about 8000 children in Sweden are affected. When the children get sick, they get in touch with interprofessional diabetes team, a contact they keep until their 18th birthday. There are several benefits to teamwork and the interprofessional teams are appreciated by staff, patients, and relatives. The team’s competence and composition are of great importance in the care of the families. Motive: The goal is to contribute with an increased understanding of the support that interprofessional teams can contribute with and possibly find proposals for development and improvement work in diabetes care. Aim: The aim of the study is to find out parent’s experience of the support from the diabetes team.Methods: A qualitative interview study.Result: The parent´s experiences of the diabetes team´s support was permeated by positivity, but also showed a certain lack of parental support. The results of the interviews resulted in 3 main categories: “Supportive relationship”, “Support in suffering” and “Support in everyday life”.  Conclusion: To meet the parent´s need for support, a change in the work of the diabetes team is required. A more individualized care, where parent´s psychosocial needs are also including, which benefits the whole family. / <p>Presenationen genomfördes via zoom, anordnad av Instutionen för omvårdnad, Umeå Universitet</p>

No abstract available. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Clinical Epidemiology / unrestricted

Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...