Background and aims: Type 2 Diabetes Mellitus (T2DM) presents a significant global health challenge, characterized by impaired insulin secretion and/or action. A critical aspect of managing T2DM involves understanding the regulatory mechanisms of insulin secretion in pancreatic β-cells. Pancreatic β-cells play a pivotal role in maintaining glucose homeostasis. Although glucose is the primary stimulator of insulin secretion, certain amino acids also have regulatory roles. Traditional views have held that while glutamine contributes to insulin secretion, it does not directly influence this process in the absence of glutamate dehydrogenase (GDH) activation. We found that glutamine increases insulin secretion independently of GDH activation in INS-1 832/13 cells. Therefore, the aim of the thesis is to elucidate the role of glutamine in insulin secretion and examining its regulatory effects on glucose metabolism in pancreatic β-cells. To achieve this, we leverage advanced methodologies, including metabolomics and network analysis, to provide a comprehensive understanding of these complex mechanisms. Methods and results: Our initial findings presented a surprising challenge to the conventional belief that glutamine induces insulin secretion only in the presence of leucine. We discovered that glutamine (independent of leucine) could increase insulin secretion in a dose-dependent manner in INS-1 832/13 cells. To delve further into this phenomenon, we employed inhibitors of key enzymes in glutamine metabolism - GDH (responsible for glutamate oxidation) and glutaminase (converts glutamine to glutamate). Our results highlighted that while inhibiting GDH did not alter insulin secretion, inhibiting glutaminase significantly reduced the insulin-secretory response to glutamine in INS-1 832/13 cells. This finding indicated that the effect of glutamine on insulin secretion operates independently of glutamate oxidation. Our study also investigated the regulatory role of glutamine in insulin secretion and on the rate of glucokinase (GK) in response to glucose levels. We observed that increasing concentrations of glutamine affected both the dynamics of insulin secretion and the kinetic parameters of GK in INS-1 832/13 cells, suggesting a regulatory relationship between glutamine and glucose phosphorylation that had not been previously observed. To deepen our understanding of the intricate relationship, we developed a novel analytical approach that combined network analysis with metabolomics. This innovative method provided an unbiased assessment of the interrelationships between various metabolites, enabling a more comprehensive understanding of the metabolic pathways and their interactions. A striking outcome of our network analysis was the identification of proline as a key metabolite in the glutamine-glucose crosstalk. To validate this link, we conducted siRNA knockdown experiments targeting proline synthesis in INS-1 832/13 cells. Knockdown of these genes resulted in a significant reduction in insulin secretion in response to glutamine. Further, this effect could be rescued by the addition of proline, thereby underscoring the essential role of proline in glutamine-mediated insulin secretion. Furthermore, in vitro enzymatic assays using INS-1 832/13 cell extracts and purified rat GK revealed proline- mediated changes in kinetic parameters consistent with glutamine-mediated alterations in GK activity in live INS-1 832/13 cells. Additionally, a thermal stability assay demonstrated that the melting temperature of purified rat GK varied with proline concentration, suggesting a direct interaction of proline with GK. This effect of glutamine on insulin secretion was also observed in isolated rat islets, thereby affirming the physiological relevance of our results. Moreover, the thermal stability assay using purified human GK confirmed that this interaction is conserved in humans as well. Conclusion and outlook: This study reveals a novel mechanism by which glutamine metabolism, through proline synthesis, regulates GK activity and thereby influences insulin secretion in pancreatic β-cells. The outlook of this thesis opens promising avenues for future research and potential clinical applications, particularly in the context of T2DM management. Key areas for future exploration include translating these findings to in vivo models and clinical settings could open new therapeutic avenues for T2DM, emphasizing the importance of modulating glutamine and proline metabolism for more effective regulation of insulin secretion. Investigating the direct causal relationship between plasma proline levels and diabetic conditions could not only deepen our understanding of diabetes but also provide a potential biomarker for early risk assessment. Understanding the precise molecular interactions between proline and GK could allow the identification of potential novel binding sites for therapeutic intervention to enhance GK activity and improve glucose regulation. Extending this research to human cells and examining its implications in diabetes and other metabolic disorders is a vital next step, offering potential for significant advancements in diabetes treatment and understanding of metabolic diseases.:Table of Contents List of abbreviations List of figures List of tables 1. Introduction 1.1. Type 2 Diabetes 1.1.1. Definition, epidemiology, and risk factors 1.1.2. Pathophysiology of T2DM 1.1.3. Preserving or enhancing β-cell function 1.2. Physiology of pancreatic β-cells 1.2.1. Overview of glucose-stimulated insulin secretion 1.2.2. Regulation of glucose entry into the β-cells 1.2.3. Role of glucokinase as a glucose sensor 1.2.4. Regulation of mitochondrial metabolism in insulin secretion 1.2.5. Regulation of amino acid mediated insulin secretion 1.3. Metabolomics approach in studying β-cell function 1.4. Network analysis in metabolomics data analysis and interpretation 2. Aims of the study 3. Materials and Methods 3.1. Materials 3.1.1. INS-1 832/13 cells 3.1.2. Chemicals, solutions, and buffers for cell culture 3.1.3. Chemicals, solutions, and buffers for molecular and metabolic experiments 3.1.4. Software 3.2. Methods 3.2.1. Cell culture 3.2.1.1. Culturing INS-1 832/13 cells 3.2.1.2. Cryopreservation and thawing of INS1 832/13 cells 3.2.1.3. Isolation of rat islets 3.2.2. Expression and Purification of GST-fusion GK Proteins in E. coli. 3.2.3. Insulin secretion studies in INS1 832/13 cells 3.2.3.1. Effect of Glutamine on insulin secretion 3.2.3.2. Effect of chronic and acute exposure of glutamine on insulin secretion 3.2.3.3. Glutamine-responsive insulin secretion 3.2.3.4. Effect of glutamate oxidation in glutamine-mediated insulin secretion 3.2.3.5. Effect of glutamine on glucose-responsive insulin secretion 3.2.3.6. Effect of 2DG on glucose stimulated insulin secretion 3.2.3.7. Insulin and total protein quantification 3.2.4. Metabolomic experiments in INS-1 832/13 cells 3.2.4.1. Effect of specific perturbations on metabolomic profile 3.2.4.2. Effect of glutamine on metabolomic profile 3.2.5. Metabolomic analyses 3.2.5.1. LC-MS/MS method for characterization of metabolites 3.2.5.2. Metabolite concentration calculation 3.2.6. Network analysis 3.2.6.1. Metabolite network construction 3.2.6.2. Comparative metabolite analysis with weighted network metrics 3.2.7. GK kinetic studies 3.2.7.1. GK activity with GK activator in INS-1 832/13 cells 3.2.7.2. GK activity with glutamine in INS1 cells & rat islets 3.2.7.3. GK kinetics measurement 3.2.7.4. In vitro GK kinetic studies using cell extracts & purified GK enzyme 3.2.8. Gene expression analysis 3.2.8.1. RNA isolation 3.2.8.2. cDNA synthesis 3.2.8.3. qPCR 4. Results 4.1. Glutamine mediated insulin secretion in INS-1 832/13 cells 4.1.1. Glutamine alone stimulates insulin secretion 4.1.2. Glutamine amplifies insulin secretion independently of glutamate oxidation 4.2. Glutamine mediated insulin secretion and its impact on glucose responsiveness 4.2.1. Glutamine modulates the regulation of insulin secretion in INS-1 832/13 cells 4.2.2. Live cell GK activity measurement using 2DG uptake in INS-1 832/13 cells 4.2.3. Glutamine modulates GK activity in INS-1 832/13 cells 4.3. Identifying the glutamine-derived factor regulating GK activity 4.3.1. Network analysis to identify key metabolites associated with specific perturbations 4.3.2. Glutamine-induced insulin secretion is mediated by proline 4.3.3. Proline modulates GK activity in INS-1 832/13 cell extracts 4.3.4. Proline modulates activity of purified rat GK 4.3.5. Thermal stability assays in rat GK 4.3.6. siRNA knockdown of proline synthesis 4.4. Glutamine modulates insulin secretion and GK activity in rat islets 4.5. Proline interacts and modulate GK in human 5. Discussion 5.1. Reevaluating glutamine-mediated insulin secretion in pancreatic β-cells 5.2. Novel role of glutamine-mediated modulation of GK activity and insulin secretion in pancreatic β-cells 5.3. Network analysis as a tool to unravel complex interactions in metabolic research 5.4. Proline as a novel modulator of GK 5.5. Contrasting role of glutamine in pancreatic and liver metabolism 6. References 7. Summary 8. Zussammenfassung 9. Acknowledgements 10. Declaration / Hintergrund und Ziele: Typ-2-Diabetes mellitus (T2DM) stellt eine bedeutende globale Herausforderung für die Gesundheit dar und ist durch eine gestörte Insulinsekretion und/oder -wirkung gekennzeichnet. Ein entscheidender Aspekt bei der Behandlung von T2DM ist das Verstehen von Regulationsmechanismen der Insulinsekretion in den β-Zellen der Pankreas. Die β-Zellen der Bauchspeicheldrüse spielen eine zentrale Rolle bei der Aufrechterhaltung der Glukosehomöostase. Obwohl Glukose der primäre Stimulator der Insulinsekretion ist, spielen bestimmte Aminosäuren auch eine regulierende Rolle. Nach traditioneller Auffassung trägt Glutamin zwar zur Insulinsekretion bei, hat aber keinen direkten Einfluss auf diesen Prozess, es sei denn, er wird durch Glutamatdehydrogenase (GDH) aktiviert. Wir fanden heraus, dass Glutamin die Insulinsekretion unabhängig von der GDH-Aktivierung in INS-1 832/13-Zellen erhöht. Ziel dieser Arbeit war es daher, die Rolle von Glutamin bei der Insulinsekretion aufzuklären und seine regulierenden Effekte auf den Glukosestoffwechsel in β-Zellen der Pankreas zu untersuchen. Um dies zu erreichen, nutzen wir fortschrittliche Methoden, einschließlich Metabolomik- und Netzwerkanalysen, um ein umfassendes Verständnis dieser komplexen Mechanismen zu erlangen. Methoden und Ergebnisse: Unsere anfänglichen Ergebnisse stellten eine überraschende Inhomogenität zur herkömmlichen Annahme dar, dass Glutamin die Insulinsekretion nur in der Anwesenheit von Leucin induziert. Wir entdeckten, dass Glutamin (unabhängig von Leucin) die Insulinsekretion in INS-1 832/13-Zellen dosisabhängig steigern kann. Um dieses Phänomen näher zu untersuchen, setzten wir Hemmstoffe von Schlüsselenzymen des Glutaminstoffwechsels ein - GDH (verantwortlich für die Glutamatoxidation) und Glutaminase (konvertiert Glutamin zu Glutamat). Unsere Ergebnisse zeigten, dass die Hemmung der GDH die Insulinsekretion nicht modifizierte, während die Hemmung der Glutaminase die Insulinsekretionsantwort auf Glutamin in INS-1 832/13-Zellen deutlich verringerte. Diese Erkenntnis deutet darauf hin, dass die Wirkung von Glutamin auf die Insulinsekretion unabhängig von der Glutamatoxidation ist. In dieser Studie untersuchten wir weiterhin die regulatorische Rolle von Glutamin bei der Insulinsekretion und für die GK-Rate in Abhängigkeit vom Glukosespiegel. Wir stellten fest, dass steigende Glutaminkonzentrationen sowohl die Dynamik der Insulinsekretion als auch die kinetischen Parameter der Glucokinase (GK) in INS-1 832/13-Zellen beeinflussten, was auf eine bisher nicht erkannte regulatorische Beziehung zwischen Glutamin und Glukosephosphorylierung schließen lässt. Um unser Verständnis dieser komplexen Beziehung zu vertiefen, entwickelten wir einen neuartigen analytischen Ansatz, der die Netzwerkanalyse mit der Metabolomforschung kombinierte. Diese innovative Methode ermöglichte eine unvoreingenommene Bewertung der Wechselbeziehungen zwischen verschiedenen Metaboliten und damit ein umfassenderes Verständnis der Stoffwechselwege und ihrer Wechselwirkungen. Ein bemerkenswertes Ergebnis unserer Netzwerkanalyse war die Identifizierung von Prolin als Schlüsselmetabolit im Glutamin-Glukose-Crosstalk. Um diese Verbindung zu bestätigen, führten wir siRNA-Knockdown-Experimente durch, die auf die Prolinsynthese in INS-1 832/13-Zellen abzielten. Die Ausschaltung dieser Gene führte zu einer deutlichen Verringerung der Insulinsekretion als Reaktion auf Glutamin. Bemerkenswerterweise konnte dieser Effekt durch die Zugabe von Prolin wiederhergestellt werden, was die wesentliche Rolle von Prolin bei der Glutamin-vermittelten Insulinsekretion unterstreicht. Darüber hinaus ergaben in vitro Enzymassays mit INS-1 832/13-Zellextrakten und gereinigter Ratten-GK Prolin-vermittelte Veränderungen der kinetischen Parameter, die mit Glutamin-vermittelten Veränderungen der GK-Aktivität in lebenden INS-1 832/13-Zellen übereinstimmen. Darüber hinaus zeigte ein Thermal Stability Assay, dass die Schmelztemperatur von gereinigtem Ratten-GK mit der Prolin-Konzentration variierte, was auf eine direkte Interaktion von Prolin mit der GK hindeutet. Dieser Effekt von Glutamin auf die Insulinsekretion wurde auch in aus Ratten isolierten Langerhansschen Inseln beobachtet, was die physiologische Relevanz unserer Ergebnisse bestätigt. Darüber hinaus bestätigte der Thermal Stability Assay mit gereinigter menschlichen GK, dass diese Interaktion auch beim Menschen konserviert ist. Schlussfolgerung und Ausblick: Diese Studie enthüllt einen neuartigen Mechanismus, durch den der Glutamin-Stoffwechsel über die Prolin-Synthese die GK-Aktivität reguliert und dadurch die Insulinsekretion in den β-Zellen der Bauchspeicheldrüse beeinflusst, was bestehende Paradigmen in Frage stellt. Perspektivisch ermöglichen die Erkenntnisse dieser Arbeit vielversprechende Wege für die zukünftige Forschung und potenzielle klinische Anwendungen, insbesondere im Zusammenhang mit T2DM-Management. Zu den Schlüsselbereichen der zukünftigen Forschung gehören die Übertragung dieser Ergebnisse auf in vivo Modelle und klinische Studien, die neue therapeutische Wege für T2DM eröffnen könnten und die Bedeutung der Modulation des Glutamin- und Prolin-Stoffwechsels für eine effektivere Regulierung der Insulinsekretion unterstreichen. Die Untersuchung des direkten kausalen Zusammenhangs zwischen Plasmaprolinspiegeln und diabetischen Erkrankungen könnte nicht nur unser Verständnis von Diabetes vertiefen, sondern auch einen potenziellen Biomarker für eine frühzeitige Risikobewertung liefern. Die Entschlüsselung der genauen molekularen Wechselwirkungen zwischen Prolin und GK könnte die Identifizierung potenzieller neuer Bindungsstellen für therapeutische Eingriffe zur Steigerung der GK- Aktivität und zur Verbesserung der Glukoseregulierung ermöglichen. Die Erweiterung dieser Forschung auf menschliche Zellen und die Untersuchung ihrer Auswirkungen auf Diabetes und andere Stoffwechselstörungen ist ein wichtiger nächster Schritt, der das Potenzial für bedeutende Fortschritte bei der Behandlung von Diabetes und dem Verständnis von Stoffwechselkrankheiten bietet.:Table of Contents List of abbreviations List of figures List of tables 1. Introduction 1.1. Type 2 Diabetes 1.1.1. Definition, epidemiology, and risk factors 1.1.2. Pathophysiology of T2DM 1.1.3. Preserving or enhancing β-cell function 1.2. Physiology of pancreatic β-cells 1.2.1. Overview of glucose-stimulated insulin secretion 1.2.2. Regulation of glucose entry into the β-cells 1.2.3. Role of glucokinase as a glucose sensor 1.2.4. Regulation of mitochondrial metabolism in insulin secretion 1.2.5. Regulation of amino acid mediated insulin secretion 1.3. Metabolomics approach in studying β-cell function 1.4. Network analysis in metabolomics data analysis and interpretation 2. Aims of the study 3. Materials and Methods 3.1. Materials 3.1.1. INS-1 832/13 cells 3.1.2. Chemicals, solutions, and buffers for cell culture 3.1.3. Chemicals, solutions, and buffers for molecular and metabolic experiments 3.1.4. Software 3.2. Methods 3.2.1. Cell culture 3.2.1.1. Culturing INS-1 832/13 cells 3.2.1.2. Cryopreservation and thawing of INS1 832/13 cells 3.2.1.3. Isolation of rat islets 3.2.2. Expression and Purification of GST-fusion GK Proteins in E. coli. 3.2.3. Insulin secretion studies in INS1 832/13 cells 3.2.3.1. Effect of Glutamine on insulin secretion 3.2.3.2. Effect of chronic and acute exposure of glutamine on insulin secretion 3.2.3.3. Glutamine-responsive insulin secretion 3.2.3.4. Effect of glutamate oxidation in glutamine-mediated insulin secretion 3.2.3.5. Effect of glutamine on glucose-responsive insulin secretion 3.2.3.6. Effect of 2DG on glucose stimulated insulin secretion 3.2.3.7. Insulin and total protein quantification 3.2.4. Metabolomic experiments in INS-1 832/13 cells 3.2.4.1. Effect of specific perturbations on metabolomic profile 3.2.4.2. Effect of glutamine on metabolomic profile 3.2.5. Metabolomic analyses 3.2.5.1. LC-MS/MS method for characterization of metabolites 3.2.5.2. Metabolite concentration calculation 3.2.6. Network analysis 3.2.6.1. Metabolite network construction 3.2.6.2. Comparative metabolite analysis with weighted network metrics 3.2.7. GK kinetic studies 3.2.7.1. GK activity with GK activator in INS-1 832/13 cells 3.2.7.2. GK activity with glutamine in INS1 cells & rat islets 3.2.7.3. GK kinetics measurement 3.2.7.4. In vitro GK kinetic studies using cell extracts & purified GK enzyme 3.2.8. Gene expression analysis 3.2.8.1. RNA isolation 3.2.8.2. cDNA synthesis 3.2.8.3. qPCR 4. Results 4.1. Glutamine mediated insulin secretion in INS-1 832/13 cells 4.1.1. Glutamine alone stimulates insulin secretion 4.1.2. Glutamine amplifies insulin secretion independently of glutamate oxidation 4.2. Glutamine mediated insulin secretion and its impact on glucose responsiveness 4.2.1. Glutamine modulates the regulation of insulin secretion in INS-1 832/13 cells 4.2.2. Live cell GK activity measurement using 2DG uptake in INS-1 832/13 cells 4.2.3. Glutamine modulates GK activity in INS-1 832/13 cells 4.3. Identifying the glutamine-derived factor regulating GK activity 4.3.1. Network analysis to identify key metabolites associated with specific perturbations 4.3.2. Glutamine-induced insulin secretion is mediated by proline 4.3.3. Proline modulates GK activity in INS-1 832/13 cell extracts 4.3.4. Proline modulates activity of purified rat GK 4.3.5. Thermal stability assays in rat GK 4.3.6. siRNA knockdown of proline synthesis 4.4. Glutamine modulates insulin secretion and GK activity in rat islets 4.5. Proline interacts and modulate GK in human 5. Discussion 5.1. Reevaluating glutamine-mediated insulin secretion in pancreatic β-cells 5.2. Novel role of glutamine-mediated modulation of GK activity and insulin secretion in pancreatic β-cells 5.3. Network analysis as a tool to unravel complex interactions in metabolic research 5.4. Proline as a novel modulator of GK 5.5. Contrasting role of glutamine in pancreatic and liver metabolism 6. References 7. Summary 8. Zussammenfassung 9. Acknowledgements 10. Declaration

Introduktion: Kardiovaskulära sjukdomar är en av de vanligaste sjukdomarna världen över och står årligen för 18 miljoner dödsfall, en tredjedel av alla dödsfall. En av dessa sjukdomar är diabetes som en av elva i världen har i någon form och mörkertalet är stort. Typ 2-diabetes (T2D) kan vara ärftlig men är också påverkbart. Riskfaktorerna kan förebyggas genom en hälsosam livsstil som innefattar fysisk aktivitet och hälsosam kost, som kan reducera övervikt. En skyddsfaktor är frukt och grönsaker, något som en vegansk diet till stora delar består av. Syfte: Syftet med denna studie är att genom två perspektiv (primär- och sekundärprevention) undersöka om en vegansk kost minskar risken för T2D. Metod: Med en strukturerad litteraturstudie har datainsamling skett via databaser PubMed och Cochrane Library. Vald analysmetod var innehållsanalys. Resultat: Från 21 granskade artiklar framkom sex olika kategorier: 1) Prevention, prevalens och incidens av T2D (veganer löper lägre risk att drabbas av T2D); 2) Vikt, BMI och kroppsmått (en vegansk kost främjar viktnedgång och sänkt BMI vid övervikt); 3) Blodvärden och blodtryck (både systoliskt och diastoliskt blodtryck, HbA1c, glukos, c-peptid, betacellsfunktion och insulinkänslighet förbättras av en vegansk kost); 4) Hormoner (GLP-1, GIP, PYY och amylin optimeras av en vegansk kost); 5) Metabolism (TMAO minskar medan och postprandial metabolism stärks av vegansk kost); och 6) Kolesterol (vegansk kost förbättrar värden för LDL, HDL samt triglycerider). Slutsats: I sin helhet visade resultatet på att en vegansk kost kan minska risken för T2D bland vuxna (≥18 år) på både primär och sekundär nivå. / Introduction: Cardiovascular disease (CVD) is one of the most common diseases worldwide and accounts for 18 million deaths annually, which is one-third of all deaths. One risk factor for CVD is type 2 diabetes (T2D). Globally, one in eleven persons has T2D and undetected cases are high. T2D can be hereditary but people can also be susceptible to T2D. The risk factors can be prevented through a healthy lifestyle including physical activity and healthy diet, which can reduce obesity. A protective factor is dietary intake of fruits and vegetables, something that a vegan diet largely contains. Aim: The aim of this study is to investigate through two perspectives (primary and secondary prevention) whether a vegan diet reduces the risk of T2D. Methods: A systematic literature review accomplished data collection using two databases, PubMed and the Cochrane Library. The analysis method chosen was content analysis. Results: Of 21 articles reviewed, six different categories emerged: 1) prevention, prevalence and incidence of type 2 diabetes (vegans are at lower risk of developing T2D); 2) body weight, body mass index (BMI) and body measurements (a vegan diet promotes weight loss, decreased BMI); 3) Blood values and blood pressure (systolic and diastolic blood pressure, HbA1c , glucose, c-peptide, beta cell function and insulin sensitivity are enhanced by a vegan diet); 4) Hormones (GLP-1, GIP, PYY and amylin are optimized by a vegan diet); 5) Metabolism (TMAO decreases and postprandial metabolism is enhanced by vegan diet); and 6) Cholesterol (vegan diet improves LDL, HDL and triglycerides). Conclusion: The results showed that a vegan diet can reduce the risk of type 2-diabetes among adults (≥18 years) at both primary and secondary levels.

Vasopressin är ett viktigt hormon som har många fysiologiska funktioner, däribland upprätthållandet av vätskebalansen i kroppen. Mätning av detta hormon är dock komplicerat och därför används ”skuggfragmentet” copeptin, som härstammar från samma prekursor. Genom användandet av metoden B·R·A·H·M·S KRYPTOR compact PLUS mäts copeptin. Studiens syfte är att beräkna variations-koefficienten och därmed undersöka de uppmätta värdenas reproducerbarhet. Vidare blir syftet att använda EpiHealth-kohortstudien för att validera den redan kända kopplingen mellan copeptin och förhöjt blodsocker genom en multivariant linjär regression. Vi kan i arbetet konstatera att copeptin metoden har en god reproducerbarhet, där majoriteten av de multipelt uppmätta copeptin-värdena har en inter-assay CV <8%. Vid undersökning av EpiHealth-kohorten fann vi att en ökning av copeptin var kross-sektionellt associerad med ett flertal metabola riskmarkörer, däribland fastande plasma-glukos, efter multivariant justering. Att copeptin var signifikant relaterat till denna potenta metabola riskmarkör kan tyda på att det finns ett orsakssamband mellan förhöjt vasopressin och förhöjt blodsocker, något som även tidigare studier har pekat på. Detta i sin tur visar att vasopressin kan spela en roll i utvecklandet av typ 2-diabetes. Om ett orsaks-samband föreligger undersöks nu i en stor randomiserad klinisk studie där vasopressin-nivåerna hos hälften av deltagarna sänks med hjälp av ökat vatten-intag (H2O-metab-studien). Det finns förhoppningar om att användandet av copeptin skall kunna användas i klinisk verksamhet för att riskbedöma individer avseende kardiometabola sjukdomar (däribland typ 2-diabetes). / Vasopressin is an important hormone that has many physiological functions, including the maintenance of fluid balance in the body. Measurement of this hormone is however complicated and therefore the "shadow fragment" copeptin is used, which is derived from the same precursor. Using the BRAHMS copeptin proAVP KRYPTOR method, copeptin was measured in this study. The purpose of the study is to calculate the coefficient of variation, and thus examine the reproducibility of the measured values ​. Furthermore, the aim will be to use the EpiHealth cohort study was used to validate the link between copeptin and elevated blood sugar through a multivariate linear regression. The majority of the multiple measurements of copeptin values had an inter-assay CV <8%, which indicates that the method has a good reproducibility. Examination of the EpiHealth cohort revealed that elevated copeptin was cross-sectionally associated with a number of metabolic risk markers, including fasting plasma glucose, after multivariate adjustment, a finding that is in line with previous findings from epidemiological studies. The fact that copeptin was significantly related to this potent metabolic risk marker may indicate a causal role of the vasopressin system in elevated blood glucose and may play a role in the development of type 2 diabetes metillus. Previous experimental and genetical studies have indicated a causal association between elevated vasopressin and diabetes development. Currently, a randomized clinical trial is ongoing (the H2O-metab-study) in order to investigate a possible causal association between elevated vasopressin and glucose. In the study, increased water intake is used to lower plasma vasopressin (measured as copeptin), and the glucose-lowering potential of this water treatment is tested. There are hopes that copeptin can in the future be used in clinical practice for risk assessment with respect to cardiometabolic diseases (including type 2 diabetes).

Background: One of the most prevalent diseases in the world, type 2 diabetes mellitus is rising every year. Self-care refers to controlling one's own illness to prevent future complications. The nurses' work is oriented on a person-centered approach to inform, promote, encourage, and support the patient to maintain good health in consideration of their circumstances. Aim: The aim of this literature study was to describe persons' experiences with self-care of type 2 diabetes mellitus.   Method: A literature study based on qualitative scientific articles which were retrieved from PubMed and CINAHL. A thematic analysis was used to analyze the articles. The study's objective was accomplished.  Results: The two main themes were identified. Experiences that affect self-care and Experiences of self-care’s impact on life.  Conclusion: Self-care is influenced by several factors such as knowledge, experience of support and control. The self-care and adaptation required for these affects the lives of people with type 2 Diabetes. Nurses have a key role in patients' self-care by helping people manage self-care. / Bakgrund: En av de vanligaste sjukdomarna i världen, typ 2 diabetes mellitus ökar varje år. Egenvård avser att kontrollera sin egen sjukdom för att förhindra framtida komplikationer. På grund av detta är sjuksköterskornas arbete inriktat på ett personcentrerat förhållningssätt för att informera, främja, uppmuntra och stödja patienten att bibehålla en god hälsa med hänsyn till sina omständigheter. Syfte: Syftet med denna litteraturstudie var att beskriva personers erfarenheter av egenvård av typ 2 diabetes mellitus. Metod: En litteraturstudie baserad på kvalitativa vetenskapliga artiklar som hämtats från PubMed och CINAHL. En tematisk analys användes för att analysera artiklarna. Studiens mål uppnåddes. Resultat: Två huvudteman identifierades. Erfarenheter som påverkar egenvården och erfarenheter av egenvårdens påverkan på livet. Slutsats: Egenvården påverkar flera faktorer såsom kunskap, erfarenhet av stöd och kontroll. Egenvården och anpassningen som krävs för dessa påverkar livet hos personer med typ 2 diabetes mellitus. Sjuksköterska har en nyckelroll i patienters egenvård genom att hjälpa personer att hantera egenvården.

Introduktion: Fysisk aktivitet är viktigt för både psykiskt och fysiskt välbefinnande. Idag är vi allt mer fysisk inaktiva och stillasittande ökar. Fysisk aktivitet minskar risken för bland annat hjärt- och kärlsjukdomar och typ 2-diabetes. För de som har typ 2- diabetes eller graviditetsdiabetes funkar fysisk aktivitet även behandlande. I takt med digitaliseringens framfart ökar hälsoappar. Dessa har potential att främja hälsosamma beteendeförändringar. Syfte: Syftet med studien var att utvärdera vad för faktorer i hälsoappar som gör att vissa hälsoappar är effektiva för att öka fysisk aktivitet hos vuxna individer med risk för typ 2-diabetes, diagnostiserad typ 2- diabetes eller graviditetsdiabetes. Metod: Studien genomfördes som en systematisk litteraturstudie med 12 vetenskapliga artiklar. Studien analyserades genom en tematisk analys. Resultat: Effektiva appar är multifaktoriella, fler faktorer påverkar. Analysen genererades i tre teman; användarupplevelse och engagemang, beteendeteorier och funktioner i hälsoappar. Dessa tre teman är viktiga för att lyckas med beteendeförändring i en hälsoapp. Användarupplevelse och engagemang kan främjas genom regelbunden feedback. Även individanpassade mål kan ge bra effekt på engagemanget för hälsobeteenden. Appdesign som integrerar beteende teorier kan stödja motivation och hjälpa användare att övervinna hinder för fysisk aktivitet. Slutsats: Effektiva hälsoappar är multifaktoriella och kräver integration av funktioner som förbättrar användarupplevelsen, inkorporerar beteendeteorier och anpassas efter målgruppen för att stödja beteendeförändring. Framtida forskning bör fokusera på att utvärdera del ångsiktiga effekterna av digitala hälsointerventioner för att främja hållbara beteendeförändringar över tid. / Introduction: Physical activity is crucial for both physical and mental well-being. Unfortunately, society is becoming increasingly physically inactive, leading to more sedentary lifestyles. Engaging in physical activity reduces the risk of diseases such as cardiovascular conditions and type 2 diabetes. For individuals with type 2 diabetes or gestational diabetes, physical activity can be an important part of treatment. The rise of digitalization has brought about a proliferation of health apps, which have the potential to promote healthy behavior changes. Purpose: The purpose of the study was to evaluate the factors in health apps that make some of them effective in increasing physical activity among adults at risk for type 2 diabetes, diagnosed with type 2 diabetes, or gestational diabetes. Method: The study was conducted as a systematic literature review with 12 scientific articles. The analysis was performed using thematic analysis. Results: Effective health apps are multifactorial, influenced by multiple factors. The analysis generated three themes: user experience and engagement, behavioral theories, and app functionalities. These three themes are crucial for achieving behavior change in a health app. User experience and engagement can be enhanced through regular feedback. Additionally, personalized goals can positively impact engagement in health behaviors. App design that integrates behavioral theories can support motivation and help users overcome barriers to physical activity. Conclusion: Effective health apps are multifactorial and require the integration of features that enhance user experience, incorporate behavior theories, and are tailored to the target audience to support behavior change. Future research should focus on evaluating the long-term effects of digital health interventions to promote sustainable behavior changes over time.

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