Introduktion: Typ 1-diabetes innebär ett betydande behov av egenvård, där hantering avhypoglykemi utgör en central del. För att underlätta denna egenvård ges patienter med typ 1-diabetes tillgång till kontinuerlig glukosmätning (CGM), där diabetessjuksköterskan spelar enviktig roll genom att erbjuda relevant undervisning och stöd. Syfte: Syftet med studien var att utforska upplevelser och hantering av hypoglykemi hospersoner med typ 1 diabetes som använder kontinuerlig glukosmätning. Metod: Kvalitativ intervjustudie med induktiv ansats valdes för att besvara syftet. Åttasemistrukturerade intervjuer genomfördes antingen på plats eller via telefon på två olikadiabetesmottagningar. Intervjuerna transkriberades ordagrant och analyserades med hjälp avkvalitativ innehållsanalys. Resultat: Analysen resulterade i tre huvudkategorier samt sex subkategorier, därhuvudkategorierna var: “Hypoglykemi- en del av vardagen”, “Hantering av hypoglykemi”och “Integrering av CGM i vardagen”. Det framkom att samtliga deltagare hade erfarenheterav hypoglykemi, och hade hittat olika strategier för att hantera detta. CGM upplevdes som enstor hjälp i vardagen samt vid hypoglykemihantering, och stödet från sjukvården samtnärstående var också väsentligt för att känna sig trygg i sin hantering. Slutsats: Deltagarnas varierande upplevelser av hypoglykemi resulterade i olika strategier förhantering i vardagen. Kontinuerlig glukosmätning utgör ett värdefullt stöd vid hanteringen avdiabetes och kan bidra till att upptäcka hypoglykemi innan den blir allvarlig. / Introduction: Type 1 diabetes is a disease that places great demands on self-care, wherehypoglycemia and its management are included. To help manage self-care, patients with type1 diabetes are offered continuous glucose monitoring (CGM), where the diabetes nurseshould offer relevant education and support. Aim: The aim of the study was to explore the experiences and management of hypoglycemiain people with type 1 diabetes using continuous glucose monitoring. Methods: Qualitative interview study with an inductive approach was chosen to answer thepurpose. Eight semistructured interviews were conducted on site or via telephone at twodifferent diabetes clinics. The interviews were transcribed verbatim and analyzed usingqualitative content analysis. Results: The analysis yielded three main categories and six subcategories. These maincategories included: "Hypoglycemia - a facet of daily life," "Management of hypoglycemia,"and "Integration of CGM in daily life." It was evident that all participants had experiencedhypoglycemia and had adopted various strategies to cope with it. CGM was experienced as agreat help in everyday life and in hypoglycemia management, and the support from thehealthcare system and relatives was also essential to feel confident in their management. Conclusion: The diverse experiences of hypoglycemia among participants have led to thedevelopment of various strategies for coping with hypoglycemia in their daily lives.Continuous glucose monitoring serves as a valuable tool in diabetes management and can aidindividuals with type 1 diabetes in detecting hypoglycemia before it becomes severe.

<p dir="ltr">Spatial transcriptomics improves transcriptomic studies by incorporating RNA localization information, which provides a more profound insight into cellular functions, interactions between cells, and their reactions to external stimuli. Single-molecule fluorescent in situ hybridization (smFISH) is a commonly utilized technique in spatial transcriptomics that allows for the accurate visualization of mRNA distribution in cells. This method aids in the quantitative evaluation of mRNA localization patterns by utilizing various physical properties, thereby illuminating processes such as transcription, nuclear export, and localized translation. Nevertheless, existing computational approaches for analyzing smFISH images often have constraints, concentrating primarily on cellular expression or specific biological contexts while overlooking broader physical analysis. In my PhD research, I created STProfiler, a comprehensive tool aimed at an unbiased physical examination of mRNA distribution. STProfiler includes an image analysis workflow that processes raw biological images to effectively detect mRNA and nuclei. It also employs machine learning techniques to biologically interpret mRNA spatial characteristics and categorize cells based on these features. My dissertation illustrates the use of STProfiler in multiple studies investigating the transcriptomic profiles of β-cells during the progression of type 1 diabetes (T1D), uncovering spatial transcriptomic diversity in β-cells. These investigations involve analyzing mRNA clusters and stress granules in pancreatic β-cells, measuring the physical characteristics of mRNAs linked to cellular stress and inflammation in mice developing T1D, evaluating the rise in HLA-DMB mRNA spliced variant in T1D, and exploring miRNA as a potential biomarker for T1D. Furthermore, STProfiler has also proven beneficial in tissue-wide spatial transcriptomics by creating masks for nuclei and cells from biological images and assigning mRNA transcripts to develop subcellular expression profiles. This capability allows for more thorough bioinformatic evaluations. In summary, STProfiler serves as a robust tool for both cell- and tissue-level spatial transcriptomics, offering an unbiased platform for researchers to investigate complex transcriptomic variations within cells.</p>

To the Editor: The recent fndings of Hummel et al demonstrate the potential clinical benefts of identifying children with presymptomatic type 1 diabetes [1]. The authors compared children who developed type 1 diabetes after a previous diagnosis of presymptomatic type 1 diabetes in the Fr1da study with those in a registry cohort of children diagnosed without a prediagnosis [aus dem Brief]

The current study aimed to examine current diabetes outcomes within the context of past and present relationships for type 1 diabetics. To qualify for the study, participants had to have been diagnosed with type 1 diabetes prior to the age of 18 and reported that they were currently in a committed romantic relationship. Relationships have been known to impact diabetes management practices; however, the impact of the long-term impact of shared management for adolescents with their parents has never been examined. Additionally, the current romantic relationship has been shown to have an impact, as well, so romantic relationships were also included in the study. Family systems theory suggests that relationships across the lifespan have a significant impact on across the lifespan. Within the context of diabetes management, family systems theory suggests that the role of the parent in shared management in adolescence may have a long-term effect on diabetes management in adulthood. Therefore, it was hypothesized that the parent-child relationship dynamics related to diabetes in adolescence would be associated with current diabetes management outcomes in adulthood. Further, it was hypothesized that this relationship would remain when current romantic relationship dynamics were considered. The current study recruited n = 123 adult participants with type 1 diabetes who were currently in a committed romantic relationship. Participants completed an online survey focused on their relational experiences related to diabetes in adolescence and in the context of their current romantic relationship. The survey assessed the diabetes outcomes of general blood sugar management, the HbA1C (A1C), and emotional distress related to diabetes management. A series of multiple linear regression analyses revealed that, for the most part, a collaborative parent-child diabetes management relationship and parent-child diabetes management conflict were not associated with A1C in adulthood. However, greater parent-child conflict during adolescence was associated with greater diabetes emotional distress in adulthood. In terms of the partner relationship, unsupportive romantic partner behaviors were associated with poorer A1C and greater diabetes emotional distress, even when the parent-child variables (i.e., collaborative parent involvement, diabetes responsibility, and diabetes specific conflict) were also included in the analysis. All regressions are controlled for age. Romantic relationship quality was controlled for within the regressions that included the romantic relationship constructs. There were two notable outcomes from these analyses: 1) arguments related to diabetes management in adolescence may be related to diabetes emotional distress in adulthood, and 2) unsupportive partner behaviors may be related to worse A1C and diabetes emotional distress outcomes. Implications for future research and practice are also addressed within the study. / Doctor of Philosophy / The current study looked at how type 1 diabetes (T1D) outcomes may be related to current romantic partner relationships and the relationship dynamics in adolescence with the participant's parent. Participants in the study were diagnosed with T1D prior to the age of 18 and were currently in a committed romantic relationship. Other research has found that relationship dynamics are related to diabetes outcomes, such as the HbA1C (A1C) and emotional distress related to diabetes. Therefore, this study looked at both the family of origin experiences and the current partner relationship dynamics, as related to T1D specifically. In the current study, n = 123 participants reported on their experience managing diabetes in adolescence with their parents. To examine this, participants completed surveys related to how collaborative their parents were in adolescence, whether they or their parents carried the responsibility for different tasks, and how many topics related to diabetes they would argue about. Next, they reported on their partner's current supportive and unsupportive behaviors. The role of the parent and partner relationship were then both examined to determine if they were related to the A1C or emotional distress in adulthood. Based on these results, it was found that more arguments in adolescence were related to more diabetes specific emotional distress in adulthood. Meanwhile, it was also found that unsupportive behaviors from partners were also related to more diabetes specific emotional distress and worse A1C.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: Habib Zaghouani. "May 2008" Includes bibliographical references.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the immune-mediated destruction of insulin-producing beta-cells of pancreatic islets, culminating in critical insulin deficiency. Both genetic and environmental factors likely orchestrate an immune-mediated functional loss of beta cell mass, leading to the clinical manifestation of disease and lifelong dependence on insulin therapy. Additional evidence suggests the role of innate and adaptive immune mechanisms leading to inflammation in beta cells mediated by proinflammatory cytokines and chemokines, activation of beta-cell-reactive T cells,and failure of immune tolerance. Viral infections have been proposed as causal determinants or initiating triggers for T1D but remain unproven. Understanding the relationship between viral infections and the development of T1D is essential for T1D prevention. Importantly, virus-induced innate immune responses, particularly type I interferon (IFN-I, IFN-a/b), have been implicated in the initiation of islet autoimmunity and development of T1D. The goal of my thesis project is to investigate how the IFN-I signaling pathway affects the development of T1D using the LEW.1WR1 rat model of autoimmune diabetes. My hypothesis is that disrupting IFN-Isignaling via functional deficiency of the IFN-I interferon receptor (IFNAR) prevents or delays the development of virus-induced diabetes.For this purpose, I generated IFNAR subunit 1(IFNAR1)-deficient LEW.1WR1 rats using CRISPR-Cas9 genome editing and confirmed the functional disruption of IFNAR1. The absence of IFNAR1 results in a significant delay in onset and frequency of diabetes following poly I:C challenge and reduces the incidence of insulitis after poly I:C treatment. The frequency of diabetes induced by Kilham rat virus (KRV) is also reduced in IFNAR1-deficient LEW.1WR1 rats. Furthermore, I observe a decrease in CD8+T cells in spleens from KRV-infected IFNAR1-deficient rats relative to that in KRV-infected wild-type rats. While splenic regulatory T cells are depleted in WT rats during KRV-infection, no such decrease is observed in KRV-infected IFNAR1-deficient rats. A comprehensive bulk RNA-seq analysis reveals a decrease of interferon-stimulated genes and inflammatory gene expression in IFNAR1-deficient rats relative to wild-type rats following KRV challenge. Collectively, the results from these studies provided mechanistic insights into the essential role of virus-induced, IFN-I-initiated innate immune responses in the early phase of autoimmune diabetes pathogenesis.

Bakgrund: Att leva med en kronisk sjukdom som diabetes typ 1 kräver daglig kontroll av sin livsföring. Som ung vuxen inträffar många förändringar i livet och det kan vara en utmaning att samtidigt vara drabbad av en kronisk sjukdom och lära sig att leva med denna och de känslor som sjukdomen framkallar. Syfte: Syftet med denna litteraturöversikt är att beskriva unga vuxnas upplevelser av att leva med diabetes typ 1. Metod: Litteraturöversikt med 13 kvalitativa artiklar av olika design. Systematisk sökning av studier i databaserna Pubmed, Cinahl och PsycINFO. Resultat: I de granskade studierna framkom att leva med diabetes och samtidigt växa upp och bli vuxen upplevdes många gånger svårt. Rädsla för att vara annorlunda jämfört med andra jämnåriga, känslor av att tappa kontrollen samt rädslor inför framtid och för komplikationer var vanligt. Den unga vuxna kände sig ofta begränsad och hade svårt att integrera rutiner kring egenvården i det dagliga livet. Familj och vänner hade ofta en viktig roll för den unga vuxna men det fanns även en känsla av kluvenhet gentemot anhörigas delaktighet och sitt eget ansvar för sin sjukdom och hälsa. I kontakten med hälso- och sjukvården upplevdes en del brister och missnöje. Slutsats: Många unga vuxna upplever negativa känslor kring sin sjukdom och har svårigheter att få vardagslivet att fungera. Genom att få kännedom om hur unga vuxna med diabetes upplever sin sjukdom och livssituation kan sjuksköterskans stödjande roll utvecklas. / Background: Living with a chronic disease like type 1 diabetes requires a daily control of the lifestyle. As a young adult, several changes in life occurs. During this time of life, it might be a challenge to also have a chronic disease and learn to live with the disease and the feelings who may emerge from it. Aim: The aim of this study is to describe the experiences of young adults living with type 1 diabetes. Method: A literature review based of 13 qualitative studies with different designs. A systematic search in the databases Pubmed, Cinahl and PsycINFO was conducted. Result: The reviewed studies showed that living with diabetes while growing up and becoming an adult, many times felt difficult. Fear of being different from other peers, feelings of losing control and fears for the future and for complications was common. The young adult often felt limited and had difficulties with integrating routines for self-management in daily life. Family and friends often had an important role for the young adult. However, the young adults could feel ambivalent in family and friend’s participation in self-management and their own responsibility for their health and illness. In contact with the health services, young adult experienced some shortages and discontent. Conclusion: Many young adults experience negative feelings about their illness and have difficulties in everyday life. By gaining knowledge about how young adults with diabetes experience their disease and life situation the supporting role from the nurse can develop.

Islet transplantation is a possible curative treatment for type 1 diabetes (T1D). Currently the liver dominates as implantation site, despite the many challenges encountered at this site. Acute hypoxia in islets transplanted to muscle and omentum, two possible alternative sites, was prevailing. However, it was rapidly reversed at both implantation sites, in contrast to when islets were transplanted intraportally. At the intramuscular site hypoxia was further relieved by co-transplantation of an oxygen carrier, polymerized hemoglobin, which also improved the functional outcome. The complement system was activated after islet transplantation to muscle, but did not hamper graft function. Both mouse and human islets transplanted to omentum become well re-vascularized and have a functional blood flow and oxygenation comparable with that of endogenous islets. Animals transplanted with islets to the omentum had a superior graft function compared with animals receiving intraportal islet grafts. Alloxan-diabetic animals were cured with a low number of islets both when the islets were implanted in the omentum and muscle. The islet grafts responded adequately to both glucose and insulin and displayed a favorable mRNA gene expression profile. A challenge in diabetes research and in islet transplantation is that there are no established techniques for quantifying beta-cell mass in vivo. By using radiolabeled Exendin-4, a GLP-1 receptor agonist, beta-cell mass after transplantation to muscle of mice was quantified. The results may well be translated to the clinical setting. By comparing the pancreatic accumulation of [11C]5-hydroxy tryptophan ([11C]5-HTP) as detected by positron emission tomography (PET) in T1D patients with that of healthy controls, a 66% decrease was observed. This may in fact represent the loss of beta-cells, taking into account that other cells within the islets of Langerhans are largely unaffected in T1D.  In conclusion, the data presented support the use of alternative implantation sites for islet transplantation. In addition to improving the functional outcome this may enable more transplantations since the number of transplanted islets may be reduced. The techniques investigated for quantifying transplanted and endogenous beta-cell mass may greatly improve our knowledge of the pathophysiology of T1D and become a valuable tool for evaluation of beta-cell mass.

Mental health problems are increasing in Swedish adolescents and mortality rates are higher in this age group than among younger. 10-20% of all adolescents suffer from a chronic medical condition (CC). Few protective factors (PF) and clustering of health-risk behaviours (HRB) are frequent among adolescents with CCs. One of the most common CC in Swedish adolescents is type 1 diabetes mellitus (T1DM). Metabolic control often deteriorates during adolescence, especially in girls. Poor metabolic control is associated with increased risk for long-term complications, of which cognitive problems are common. However, the implication of cognitive/executive problems in patients with T1DM has not been sufficiently studied. Neither has the impact of neurodevelopmental problems (NDP), such as ADHD, on HRB in adolescents with CCs been analysed. Methods: In paper I and II the questionnaire ”Life and Health in Youth” was distributed to all students in year nine and year two of the upper secondary school in the county of Sörmland, 2008 (n=5771) and 2011 (n=5550). Adolescents with CCs were compared to healthy peers with regard to PFs and HRBs. In paper III, the ”Five to Fifteen” questionnaire was used in 175 paediatric patients with T1DM. Patients with indications of NDPs were compared with patients without such problems with regard to metabolic control. In paper IV, the BRIEF questionnaire and the ADHD Rating Scale as well as data from the Swedish Childhood Diabetes Registry was used in 241 adolescents with T1DM. Patients with indications of executive problems were compared with patients without such problems with regard to diabetes control. Results: CCs were associated with few PFs and clustered HRBs. The combination of CCs and low numbers of PFs was found to be associated with an increased risk of clustered HRBs. In the presence of coexisting ADHD the pattern of few PFs and clustering of HRBs was aggravated. ADHD was more common among adolescents with other CCs. Definite memory and learning problems as well as mild executive problems were associated with poor metabolic control, especially among adolescents. Executive problems were also associated with many outpatient visits and low physical activity. Girls with T1DM tended to self-report executive problems to a larger extent than boys, while parents more often reported these problems in boys. Conclusion: Knowledge about factors influencing treatment adherence and life in general is essential in the work with chronically ill adolescents. Focus must be put on enhancing PFs in order to avoid HRBs. Identification of coexisting NDPs, such as ADHD, is crucial, since such problems can adversely influence treatment adherence, HRBs and school achievements

Aims: The Childhood Diabetes Registry in Saxony, Germany, examined the incidence and metabolic characteristics of childhood diabetes. Methods: In the federal state of Saxony, newly diagnosed cases of diabetes in children and adolescents aged less than 15 years were registered continuously from 1999 until 2008. Family history, date of diagnosis, clinical and laboratory parameters were obtained. Reported cases were ascertained by public health departments as an independent data source and verified using the capture- recapture method. Results: A total of 865 children and adolescents with newly diagnosed diabetes were registered in Saxony. About 96% of them were classified as having type 1 diabetes, 0.6% had type 2 diabetes, 2.4% had maturity-onset diabetes of the young (MODY), and 1.4% had other types of diabetes. The age-standardized incidence rate of type 1 diabetes was estimated at 17.5 per 100,000 children per year. Completeness of ascertainment as calculated by the capture-recapture method amounted to 93.6%. At the time of diagnosis, 27.1% of children with type 1 diabetes had ketoacidosis, 1.5% had a blood pH <7.0, and 1.1% were unconscious. Conclusion: The registry provided data about the incidence rates and clinical presentation of childhood diabetes in a defined German population. We observed higher incidence rates compared to previous surveys. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.