Alzheimers sjukdom (AD) är den vanligaste formen av demens och kännetecknas av intracellulärt neurofibrillärt trassel (NFT) bestående av proteinet tau och extracellulära plack, uppbyggda av peptiden amyloid beta (Aβ). En växande skara studier har börjat peka mot att AD är en hjärnspecifik typ av diabetes. Insulinresistens följt av hyperinsulinemi och hyperglykemi är kännetecken för diabetes mellitus typ 2 (DMT2) och har visat sig vara en riskfaktor för AD. Insulin, ett hormon som kontrollerar glukoshomeostasen i perifera nervsystemet (PNS) och är viktigt för minne och inlärning, transporteras över blod-hjärnbarriären i en mättnadsbar transportmekanism och dess koncentration i centrala nervsystemet (CNS) minskar vid DMT2 och AD. Insulin-like growth factor 1 (IGF-1), ett neuronskyddande protein som minskar ogynnsam β-sekretasklyvning av amyloid precursor protein (APP) i amyloidkaskadhypotesen, minskar i koncentration i hjärnan när mycket insulin transporteras in i CNS. γ-sekretas ökar sin aktivitet på APP vid höga halter kolesterol som är vanligt vid DMT2, Aβ fungerar då som en negativ inhibitor till HMG-Coa reduktas (HMGR), enzymet som bildar kolesterol och kan därmed reglera kolesterolhalterna. Regleringssystem för Aβ i blod-hjärnbarriären (BBB) som p-GP, LRP-1 och RAGE rubbas vid DMT2. Aβ och insulin delar samma degraderingssystem, insulin degrading enzyme (IDE), som reglerar halterna Aβ och insulin. Dessutom har Aβ oligomerer visat sig kunna bryta ned insulinreceptorer (IR). Vidare har läkemedel mot diabetes visat sig lindra demens hos AD patienter. I den här rapporten gås de molekylärfysiologiska sambanden igenom i detalj. Slutligen finns det fog för ett samband mellan metabolt syndrom, en riskfaktor för DMT2, och AD.

Bakgrund: Diabetes mellitus typ II är en av de snabbast växande sjukdomarna i världen. Det är en kronisk endokrin sjukdom som kräver många livsförändringar och determination. Det kännetecknas främst av att bukspottkörteln producerar otillräckligt med insulin. Den främsta orsaken till diabetes typ II inkluderar riskfaktorer som ärftlighet, ohälsosam livsstil avseende dålig kost, fysisk inaktivitet, fetma och ålder. Tidiga symtom på diabetes typ II är ökad törst, frekvent urinering, trötthet och muntorrhet. Syfte: Syftet var att belysa sjuksköterskors upplevelser av att vårda patienter med diabetes mellitus typ II. Metod: En litteraturstudie baserad på 10 kvalitativa artiklar som kritiskt analyserades och sammanfattades. Sökningar som härrörde från relevanta sökord gjordes i databaserna PubMed och Cinahl. Detta bidrog till att finna relevanta studier som genomförts i olika världsdelar samt kvalitetsgranskades. Resultat: Resultatet visade att majoriteten av sjuksköterskorna upplevde  bristande strategi och oförmåga att informera patienterna gällande livsstilsförändringar. Sjuksköterskorna upplevde även att patienterna var beroende av dem och såg egenvården som en utmaning. Resultatet visade även att personcentrerad vård var avgörande för att ge effektiv vård och förbättra patienternas deltagande.  Slutsats: Sjuksköterskor behöver mer kunskap, kompetens samt organisatoriska förutsättningar, för att ge en effektiv personcentrerad vård med behandling som stödjer en person som lever med diabetes typ II. Sjuksköterskor önskade mer kunskap inom kulturella och socioekonomiska faktorer för att ge optimal vård och stärka patientens förmåga. Brist på effektivt samarbete mellan vårdpersonal inom diabetesvården identifierades också som ett hinder för god vård. / Background: Diabetes mellitus type II is one of the fastest growing disease worldwide. It is a chronic endocrine disease that requires a lot of life changes and determination. It is characterized primarily by the pancreas producing insufficient insulin. The main cause of diabetes type II includes risk factors such as heredity and unhealthy lifestyle regarding poor diet, physical inactivity, obesity and age. Early symptoms of diabetes type II are increased thirst, frequent urinary, fatigue and dry mouth. Aim: The purpose was to explore nurses´ perception in caring of patients with diabetes mellitus type II. Method: A literature review of which 10 qualitative articles were critically analyzed and summarized. Searches derived from relevant keywords were made in PUBMED and CINAHL databases. This contributed to the finding of relevant articles that were conducted worldwide and were quality-reviewed.  Result: The articles acknowledged  that the majority of the nurses perceived a lack of strategy and inability to inform patients about lifestyle changes. The result also showed that person-centered care was crucial in order to provide effective care and improve patient participation. Conclusion: Nurses need more knowledge, competence and organizational conditions in order to provide effective person-centered care with treatment that supports a person living with type II diabetes. Nurses  also required more knowledge within cultural and social economic factors in order to provide optimal care and strengthen the patient’s abilities. Lack of effective collaboration between healthcare professionals in diabetes care was also identified as an obstacle to provide good care.

Bakgrund: Diabetes Mellitus typ I är ett globalt hälsoproblem som skördar många liv varje år och påverkar livskvaliteten för de drabbade. Diabetes typ I är en autoimmun sjukdom som leder till destruktion av insulinproducerande betaceller i pankreas och således rubbad glukosreglering. Huvudsakliga patogena immunceller inkluderar autoantikroppar, exempelvis riktade mot glutaminsyra dekarboxylase 65, och autoreaktiva T-celler. Diagnos sker generellt baserat på förhöjda halter plasmaglukos och eventuellt stimulering av C-peptid för att utreda status för den endogena betacellsfunktionen. Diabeteskomplikationer är en vanlig dödsorsak hos diabetespatienter. År 2019 orsakades 4,2 miljoner dödsfall av diabetes eller diabeteskomplikationer. I dagsläget är administrering av exogent insulin enda behandlingsmöjligheten för typ I diabetespatienter. Det har dock länge forskats på alternativ i form av preventiv behandling men i dagsläget finns inga preventiva behandlingar på marknaden. Syfte: Litteraturstudiens syfte var att undersöka prospektiva möjligheter till diabetespreventiv behandling inom områdena glutaminsyra dekarboxylase 65 vaccin och coxsackievirus B vaccin med avseende på effekt samt jämföra dessa två prospektiva behandlingsmöjligheter. Metod: Arbetet har utförts genom granskning av artiklar från databasen PubMed. För litteraturgranskning av studier om GAD-behandling valdes tre kliniska studier utifrån sökning med ”type 1 diabetes”, ”diabetes mellitus”, ”type 1”, ”GAD” och ”vaccine” som sökord. För artiklar om CVB och CVB-vaccin användes ”type 1 diabetes”, ”vaccine” och ”coxsackievirus” som sökord. Resultat: Kliniska studier på GAD-behandling visar ingen signifikant skillnad mellan GAD-alum och placebo i helgruppsanalyser. Vid vissa stratifierade analyser för exempelvis kön, ålder, eller antal riskfaktorer detekteras signifikanta skillnader genom ökad mängd stimulerad C-peptid eller progression till klinisk diabetes. Den prospektiva kohortstudien över diabetesincidens påvisar att CVB är en riskfaktor för diabetes hos människa. Vidare visar de prekliniska studierna på signifikant minskad diabetesincidens i CVB-vaccinerade studiepopulationer jämfört med placebo. Slutsats: Varken behandling med GAD-alum eller CVB-vaccin är möjligt att använda som preventiv behandling i nuläget. Dock visar studierna på lovande framtidsmöjligheter för CVB-vaccin som primärprevention och GAD-alum som sekundär- eller tertiärprevention. / Background: Diabetes Mellitus type I is a global health issue, causing numerous deaths each year and also influencing the quality of life of those affected. Type I diabetes is an autoimmune disease where the individuals own immune system causes destruction of insulin producing beta cells in the endocrine islets of pancreas. Main immunological features include, autoantibodies directed towards glutamic acid decarboxylase 65, and autoreactive T-cells. Diagnosis is generally based on elevated levels of plasma glucose and stimulated C-peptide, together disclosing the status of the beta cell function. The lack of endogen insulin causes disturbances in the glucose metabolism which leads to prevailing tissue damage in cells and organs of the diabetic individual’s body. Furthermore, insufficient control of plasma glucose is related to development of diabetes complications. Diabetic complications are known to be a major cause of death in diabetic patients. Diabetes and diabetic complications caused 4,2 million deaths in 2019. Insufficient adherence to treatment regimen during a long period of time is known to increase the risk for some common diabetes complications. Administration of exogenous insulin is the only current treatment available for type I diabetes, albeit recurrent attempts to find a cure or successful preventive treatment for diabetes mellitus type I. Recent promising research on diabetes preventive treatment includes the autoantigen glutamic acid decarboxylase-65 and vaccine against coxsackievirus B. Aim: The purpose of this literature study was to examine prospective possibilities for diabetes preventive treatments. Further, the purpose was to compare the promising preventive treatments of GAD65-vaccine and CVB-vaccine concerning effect and prospective treatment regimens. Methods: The thesis is a literature study based on articles found by searching the database PubMed. Clinical studies examining the effect of GAD-treatment was found by using key words such as ”type 1 diabetes”, ”diabetes mellitus”, ”type 1”, ”GAD” and ”vaccine”. Studies examining the effect of CVB and CVB-vaccines was primarily preclinical and prospective cohort studies, found by searching for the key words ”type 1 diabetes”, ”vaccine” and ”coxsackievirus”. Results: Clinical studies of GAD-treatment does not demonstrate a statistically significant difference between treatment with GAD-alum compared to placebo in full group analysis. Stratified groups occasionally prove significant differences in quantity of stimulated C-peptide or progression to clinical diabetes by age, gender or amount of risk factors for example. The prospective cohort study examining the incidence of diabetes, demonstrates that CVB is a risk factor for type I diabetes in humans. Furthermore, the preclinical studies detect a significant decrease in diabetes incidence in CVB-vaccinated mice compared with placebo. Conclusion: Neither treatment with GAD-alum nor CVB-vaccine is currently ready for use. However, the studies show a promising prospective possibility for CVB-vaccine as a primary prevention and GAD-alum as a secondary or tertiary prevention of type I 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.

The worldwide increasing number of persons affected by largely preventable diseases like diabetes demands better prevention and treatment. Insulin is required for effective utilisation of circulating nutrients. Impaired responsiveness to insulin (insulin resistance, IR) is a hallmark of type 2 diabetes and independently raises the risk of heart attack and stroke. The pathophysiology of IR is incompletely understood. High-throughput measurement of large numbers of circulating biomarkers may provide new insights beyond established risk factors. The aims of this thesis were to (i) use proteomics, metabolomics and genomics methods in large community samples to identify biomarkers of IR; (ii) assess biomarkers for risk prediction and insights into aetiology and consequences of IR; and (iii) use Mendelian randomisation analysis to assess causality. In Study I, analysis of 80 circulating proteins in 70-to-77-year-old Swedes identified cathepsin D as a biomarker for IR and highlighted a tentative causal effect of IR on raised plasma tissue plasminogen activator levels. In Study II, nontargeted fasting plasma metabolomics was used to discover 52 metabolites associated with glycaemic traits in non-diabetic 70-year-old men. Replication in independent samples of several thousand persons provided evidence for a causal effect of IR on reduced plasma oleic acid and palmitoleic acid levels. In Study III, nontargeted metabolomics in plasma samples obtained at three time points during an oral glucose challenge in 70-year-old men identified associations between a physiologic measure of IR and concentration changes in medium-chain acylcarnitines, monounsaturated fatty acids, bile acids and lysophosphatidylethanolamines. Study IV provided evidence in two large longitudinal cohorts for causal effects of type 2 diabetes and impaired insulin secretion on raised coronary artery disease risk. In conclusion, the Studies in this thesis provide new insights into the pathophysiology and adverse health consequences of IR and illustrate the value of combining traditional epidemiologic designs with recent molecular techniques and bioinformatics methods. The results provide limited evidence for the role of circulating proteins and small molecules in IR and require replication in separate studies and validation in experimental designs.

Pharmacometric modelling is widely used in many aspects related to type 2 diabetes mellitus (T2DM), for instance in the anti-diabetes drug development, and in quantifying the disease progression of T2DM. The aim of this thesis were to improve the design of early phase anti-diabetes drug development studies with the focus on the power to identify mechanism of drug action (MoA), and to characterize and quantify the progression from prediabetes to overt diabetes, both the natural progression and the progression with diet and exercise interventions, using pharmacometrics modelling. The appropriateness of a study design depends on the MoAs of the anti-hyperglycaemic drug. Depending on if the focus is power to identify drug effect or accuracy and precision of drug effect, the best design will be different. Using insulin measurements on top of glucose has increase the power to identify a correct drug effect, distinguish a correct MoA from the incorrect, and to identify a secondary MoA in most cases. The accuracy and precision of drug parameter estimates, however, was not affected by insulin. A natural diabetes disease progression model was successfully added in a previously developed model to describe parameter changes of glucose and insulin regulation among impaired glucose tolerance (IGT) subjects, with the quantification of the lifestyle intervention. In this model, the assessment of multiple short-term provocations was combined to predict the long-term disease progression, and offers apart from the assessment of the onset of T2DM also the framework for how to perform similar analysis. Another previously published model was further developed to characterize the weight change in driving the changes in glucose homeostasis in subjects with IGT. This model includes the complex relationship between dropout from study and weight and glucose changes. This thesis has provided a first written guidance in designing a study for pharmacometrics analysis when characterizing drug effects, for early phase anti-diabetes drug development. The characterisation of the progression from prediabetes to overt diabetes using pharmacometrics modelling was successfully performed. Both the natural progression and the progression with diet and exercise interventions were quantified in this thesis.

Islet transplantation has found its niche in diabetes treatment. It has contributed to a better quality of life and better glycemic control of patients with diabetes suffering from severe hypoglycemia that are not eligible for vascularized pancreas transplantation. Islet isolation is a technically challenging procedure. The different studies within this doctoral thesis aim to improve and standardize different steps in the isolation procedure. They are in particular looking to improve human pancreas preservation during cold storage, to optimize islet release from the exocrine tissue and to assess whether the isolated islet yield can be predicted from a biopsy. We found that pancreas preservation with pre-oxygenated perfluorodecalin (two-layer method) did not improve the ischemic tolerance of the human pancreas as compared to cold storage with the University of Wisconsin (UW) solution. Furthermore, in pancreas with long cold ischemia time (CIT) (>10 hours), Histidine-Tryptophan-Ketoglutarate (HTK) had a limited preservation capacity as compared with the UW solution with respect to isolation outcome. We also found that during enzymatic pancreas digestion, Vitacyte HA was able to provide a similar islet yield and quality as Serva NB1 with less collagenase activity and shorter digestion time. We further describe the first experience with a new GMP manufactured enzyme called Liberase MTF-S for successful human islet isolation. Finally, we found that the isolated islet yield could not be predicted from a biopsy taken from the head of the pancreas concerning solely morphological parameters of the islets tissue. The improvement of pancreas preservation will allow for marginal organs with prolonged cold ischemia time to expand the donor pool. Better knowledge of how the pancreatic extracellular matrix is digested by collagenase will lead to a fast and predictable islet release from the exocrine tissue. By standardizing the isolation procedure and improving organ selection we will increase the success rate in human islet isolation, thereby making islet transplantation available for more patients.

Background: Oral contraceptives are common among female athletes. Still, its effects on athletic performance are poorly investigated. Research in the area has increased in recent years. However, the study qualities and designs are often insufficient and with small sample sizes. Women are currently underrepresented in sport research, and to recruit more women in future studies and to facilitate female athletes’ choices about contraceptives, the impact of oral contraceptives on performance must be better understood. Aim: The aim was to investigate whether monophasic, combined oral contraceptive phases affected maximal muscle strength, anaerobic performance and the corresponding blood lactate response, or perceived mental and physical energy level among young women. Method: The study used a cross-over design where six participants were tested on two occasions. The participants were healthy women between 18 and 29 years old who had beenusing monophasic combined oral contraceptives for at least three months prior to the study. No criteria for training level was set. The Isometric mid-thigh pull (N) was used as an indicator ofmaximal muscle strength; and the Wingate anaerobic test (W) measured anaerobic performance and power with corresponding blood lactate levels (mmol/L) measured at 0, 3 and 5 minutes after termination of the test. The participants rated their current physical and mental energy level on both test occasions using a visual analog scale (0-10). Statistical analyses were madeusing Wilcoxon signed-ranked test. Results: Nine participants were recruited, of which six performed tests on both occasions. The participants had a mean (SD) age of 22.3 (1.8) years, a BMI of 23.3 (2.6) and all reached WHO’sphysical activity recommendations. No statistically significant differences in muscle strengthor anaerobic performance were found regarding peak force (p=0.60), peak power (p=0.35) oraverage power (p=0.60) between oral contraceptive phases. Neither were there any differencesin the blood lactate response to the Wingate test directly after (p=0.92), 3 minutes after (p=0.17) or 5 minutes after (p=0.60) the test. No differences in perceived mental energy level (p=0.35)or perceived physical energy level (p=0.17) between oral contraceptive phases were evident. Conclusion: Oral contraceptive phases did not affect maximal muscle strength, anaerobicperformance, blood lactate response or perceived mental or physical energy levels. Accordingly, there is no need to adapt training to oral contraceptive phases and women can berecruited in future research without consideration of oral contraceptive phases.

Type 1 diabetes (T1D) is a complex chronic disease without treatment. When anindividual is diagnosed with T1D they are taught how to monitor blood glucoselevel as well as external insulin administration. While this management strategyhelps prolong the individual’s life, there are other lifestyle factors not consideredthat negatively impact the patients’ life. This thesis aims to investigate the types of data that can be gathered to benefit T1D patients and healthcare specialists by improving life quality. To do so, the work employs a literature review and its qualitative analysis, aninterviewing process and its qualitative analysis as well as overall findings analysiswhere data is interpreted in order to identify areas of interest, common topics andtrends. 43 literature publications, 3 healthcare professionals and 3 T1D patientsparticipated in this study. Results show initial education is limited leaving patients to initiate their ownresearch which could be a cause for stress. Technological integration does not seemchallenging provided the right training of more complex solutions. Education asa means to reduce stress seems effective both for patients but also for their socialnetworks. Finally, there are currently useful data markers not being used that couldprovide a wider range of information to healthcare specialists aiding in better patientcare and improved T1D patients’ Quality of Life (QOL). To conclude, T1D is a complex chronic disease that requires both clinical andnon-clinical interventions. It is not sufficient to only address its clinical implicationsbut is important to investigate factors that impact the lifestyle and quality of life. Byextracting proper data markers, collecting and analyzing them, it is believed thattechnology can assist healthcare and ultimately improve T1D patient’s quality oflife. / Diabetes typ 1 är en komplex kronisk sjukdom som inte har en behandling. När enindivid blir diagnostiserad med Diabetes typ 1 lär dem att mäta blodsocker nivåernasamt externa insulin administering. Medan denna strategi hjälps förlänga individensliv, finns där andra livsstilsfaktorer som inte är övervägd. Denna avhandling syfta mot att kunna undersöka datatyper som kan insamlas tillfördel för Diabetes typ 1 patienter och värdpersonal genom att förbättra livskvalitet. För att kunna utföra detta genomfördes en litteratursammanställning med en kvalitativ analys, intervjuer med en kvalitativ analys samt ett övergripande rön där datantolkas för att kunna identifiera områden som kan vara intressanta, allmänna temanoch trender. 43 litteratur publikationer, 3 vårdpersonal och 3 diabetes typ 1 patienterdeltog i undersökningen. Resultatet visar inledande utbildning är begränsad vilket leder till att patienterinitiera egen fördjupning. Detta kan bidra till stressnivåerna. Teknologisk integrering verka inte vara en utmaning för patienter om dem få rätt utbildning för komplexa lösningar. Utbildning som metod för att bekämpa och minska stressnivåernaverka effektivt både för patienterna och vårdpersonal men även för deras sociala nätverk. Slutligen, finns där användbara data markörer som inte används men kan förse bredare information till vårdpersonal vilket kan förbättra vården samt patientenslivskvalitet. Slutligen är diabetes typ 1 en komplex sjukdom som kräver både klinisk menäven icke-kliniska ingripande. Det är inte tillräcklig att enbart ta itu med dem kliniska ingripande men det är även viktigt att undersöka faktorer som påverkar livsstiloch livskvalitet. Genom att excerpera lämplig data markörer samt samla och analysera dem, är det tänkt att teknologi kan assistera vårdpersonal och till slut förbättralivskvaliteten av diabetes typ 1 patienter

Current diabetes care practices provide the same amount of care to everyone, regardless of individual needs. The high coverage of continuous glucose monitors (CGMs) in the Type 1 Diabetes (T1D) population can facilitate the implementation of need-based care, which could potentially largely benefit both clinics and patients. This master’s thesis develops and evaluates a simulation model to explore patient flow in T1D clinics using need-based booking, as well as a user interface for running the simulation and collecting output data. The model also serves as a tool for optimizing input parameters for this system. Utilizing Agent-Based Modeling (ABM) and Discrete Event Simulation (DES), the study includes basic validation to ensure reliability. Findings suggest that the model has been perceived as useful as a tool to discover suitable configurations of a need based booking system when used in a T1D clinic, as well as to communicate and visualise potential benefits and effects of using a need-based system for T1D patients. / Nuvarande diabetesvårdsmetoder erbjuder samma vård till alla, oavsett individuella behov. Den höga täckningen av kontinuerliga glukosmätare (CGMs) i befolkningen med Typ 1-diabetes (T1D) kan underlätta införandet av behovsstyrd vård, vilket potentiellt kan gynna både kliniker och patienter i stor utsträckning. Denna masteruppsats utvecklar och utvärderar en simuleringsmodell för att utforska patientflödet i T1D-kliniker med behovsstyrd bokning, samt ett användargränssnitt för att köra simuleringen och samla in utdata. Modellen fungerar också som ett verktyg för att optimera inmatningsparametrar för detta system. Genom att använda agentbaserad modellering (ABM) och diskret händeslestyrd simulering (DES) inkluderar studien grundläggande validering för att säkerställa tillförlitlighet. Resultaten tyder på att modellen har uppfattats som användbar som ett verktyg för att upptäcka lämpliga konfigurationer av ett behovsstyrt bokningssystem i kliniker för T1D, såval som kommunicera och visualisera potentiella fördelar och effekter av att använda behovsstyrda bokningssystem för patienter med T1D diabetes.