Bakgrund: Diabetes mellitus typ 2 (DMT2) är ett globalt växande kronisk sjukdom. Cirka 500 000 personer i Sverige lider av diabetes, varav 90 procent har diabetes typ 2. Förekomsten av DMT2 ökar bland personer som har immigrerat till Sverige, vilket bedöms orsakas av en kombination av genetiska faktorer, livsstilsfaktorer och socioekonomiska omständigheter. För att effektivt hantera sjukdomen är det avgörande med noggrann egenvård, som inkluderar regelbunden självkontroll av blodsockernivåer, anpassad kost och fysisk aktivitet. Syfte: Syftet var att beskriva erfarenheter av egenvård hos immigrerade patienter som har diabetes typ 2. Metod: Kvalitativ litteraturöversikt baserad på 13 utvalda vetenskapliga artiklar som publicerades mellan 2003–2023. Litteratur söktes i databaserna CINAHL och Medline.  Artiklarna analyserades enligt Fribergs femstegsmodell. Resultat: En rad olika faktorer påverkade patienternas upplevelse av egenvård. Bristande kommunikation och språkfärdigheter samt otillräcklig kunskap om diabetes utgjorde stora utmaningar för patienterna när det gällde att förstå sin sjukdom. Patienterna hade olika uppfattningar om varför de drabbats av sjukdomen, ofta kopplade till kulturella och religiösa orsaker. Dessutom beskrivs frustration över vårdgivarnas bemötande och svårigheter för patienterna att bibehålla livsstilsförändringar. Slutsats: Patienternas uppfattning av DMT2 och egenvård spelar en avgörande roll. Det finns ett behov av ökad kunskap om kost, motion och medicinering för att möjliggöra kontinuerlig egenvård och förbättra hälsa. Socialt stöd underlättar acceptans av förändringar i livsstilen och främjar därmed egenvården. / Background: Diabetes mellitus type 2 (DMT2) is a globally growing chronic disease. Approximately 500 000 people in Sweden suffer from diabetes, of which 90 percent have DMT2. The prevalence of DMT2 is increasing among individuals who have immigrated to Sweden, which is assessed to be caused by a combination of genetic factors, lifestyle choices and social economic circumstances. To effectively manage DMT2, self-care is crucial, including regular monitoring of blood sugar levels, a tailored diet and physical activity. Aim: Describe self-care experiences among immigrant patients with diabetes type 2. Method: Qualitative literature review based on 13 selected articles published between 2003 and 2023. Literature was searched in the CINAHL and Medline databases. The articles were analysed using Friberg’s five-step model. Results: Several factors influenced a patient’s experience in managing their self-care. Lack of communication and language skills and insufficient knowledge about diabetes posed significant challenges for patients in understanding their illness. Patients held diverse perceptions regarding the causes for their diabetes, often linked to cultural and religious reasons. Furthermore, there was frustration regarding the healthcare providers’ attitudes and difficulties for patients in maintaining lifestyle changes. Conclusions: The patients’ perception of DMT2 and self-care plays a crucial role. There’s a need for increased knowledge about diet, exercise, and medication to enable continuous self-care and improve health. Social support facilitates the acceptance of lifestyle changes, thereby promoting self-care.

Bakgrund: Sjuksköterskans specifika kompetens är omvårdnad. Personcentrerad vård fokuserar på att se varje patient som en unik person med individuella behov. Vid diabetes har sjuksköterskan en viktig pedagogisk och handledande funktion för att stärka patientens förmåga att hantera sjukdomen. Sjuksköterskans ansvarsområde vid diabetes består av att ge information och bedöma patientbehov samt ge teoretisk och praktisk utbildning till alla diabetespatienter för att underlätta egenvården. Syfte: Att beskriva personer med diabetes typ 2 erfarenheter av att utföra egenvård. Metod: En beskrivande litteraturstudie innehållande 9 kvalitativa vetenskapliga artiklar. De vetenskapliga artiklarna har hittats eftersökning i databasen PubMed. Huvudresultat: Vid sociala sammanhang förekommer det svårigheter med att hålla sin kost, vilket kan leda till skuldkänslor och bli en psykologisk börda för personer med diabetes typ 2. Flera hinder för egenvård presenterades, alla med påverkan på blodsockernivån. Användning av mobilapp resulterade i att många av användarna lärde sig tolka blodsockervärden och identifiera mönster i aktivitetsnivå, kost och blodsockernivå och samband mellan dem för att kunna hålla blodsockret på en bra nivå. Utbildning är en viktig del i att ändra beteende gällande egenvård. Tillräcklig kunskap om sjukdomen, sekundära sjukdomar och åtgärder för att påverka sjukdomen möjliggör anpassning gällande livsstilen. Slutsats: Sjuksköterskor bör arbeta personcentrerat och för att kunna göra det är det bra att de får en inblick i hur diabetes typ 2 kan påverka personens liv och att det är mer som tillhör egenvård än vad man tänker på när man hör ordet. / Background: The nurse's specific competence is nursing. Person-centered care focuses on seeing each patient as a unique person with individual needs. In the case of diabetes, the nurse has an important educational and supervisory function to strengthen the patient's ability to manage the disease, also providing information and assessing patient needs as well as providing theoretical and practical training to all diabetes patients to facilitate self-care. Purpose: To describe people with diabetes type 2 experience with self-care. Method: A descriptive literature study including 9 qualitative scientific articles. The scientific articles were found through searching the database PubMed. Main result: Social contexts can mean difficulties with maintaining one's diet and feelings of guilt. It is a psychological burden for people with type 2 diabetes. Several barriers to self-care were presented. Using the mobile app resulted in many of the users learning to interpret blood sugar values and identify patterns in activity level, diet and blood sugar level and the relationship between them to keep blood sugar at a satisfactory level. Sufficient knowledge of the disease, secondary diseases, and measures to influence the disease enable adaptation regarding the lifestyle. Conclusion: Nurses should work person-centered and to be able to do that it is good that they get an insight into how diabetes type 2 can affect the person's life and that there is more to self-care then what comes to mind when you hear the word.

The mechanical properties of the arterial wall are of great importance for blood pressure regulation and cardiac load. With increasing age, large arteries are affected by increased wall stiffness. Furthermore, atherosclerotic manifestations may increase the stiffness even further, both processes acting as independent cardiovascular risk factors affecting the arterial system in a heterogeneous way. The aims of this thesis was to characterize the local mechanical properties of brachial artery (BA) with the aid of ultrasound technique and to evaluate the influence of 1) age, gender, sympathetic stimulation and examination site; 2) type 1 diabetes (DM) and its association to circulatory biomarkers; and 3) to evaluate the general properties of the arterial system with the aid of pulse wave velocity (PWV) as well as pulse wave analysis (PWA) in systemic lupus erythematosus (SLE) and correlate the findings to disease activity and circulatory biomarkers. In the most proximal arterial segment of the upper arm a pronounced age-related decrease in wall distensibility, increase in intima-media thickness (IMT), and a slight increase in diameter were seen. Sympathetic stimulation had no influence on wall mechanics. More distally in BA, no change in diameter, and only minor increase in IMT and decrease in distensibility were seen. No gender differences were found. These findings suggest that the principle transit zone between elastic and muscular artery behaviour is located in the proximal part of the upper arm. Women with uncomplicated insulin-dependent DM had similar diameter, IMT and distensibility in their distal BA as controls, whereas flow-mediated dilatation (FMD) was slightly, and nitrate mediated dilatation (NMD) markedly reduced. NMD was negatively correlated with higher HbA1c levels. Vascular smooth muscle cell function seems to be an early manifestation of vascular disease in women with DM, influenced by long-term hyperglycaemia. Women with SLE had increased aortic PWV compared to controls, a finding positively associated with increased levels of complement factor 3 (C3), but not with disease activity. The increased stiffness of central arteries may be one factor contributing to the increased cardiovascular risk seen in SLE.

Type 1 diabetes affects a person’s life on many levels in terms of quality of life, health, and socioeconomic costs both for the patients but also their families. As of now there is no therapy that targets the underlying mechanism of the disease. Intralymphatic administration of Diamyd® is being evaluated in a phase IIb clinical trial, DIAGNODE-2. The aim was to examine if the intralymphatic administration is feasible for both patients and medical professionals, and to identify any aspects of the procedure that can be improved. This feasibility study is based on interviews and answers received from questionnaires. The medical professionals that were selected were radiologists and study nurses that are involved in the DIAGNODE-2 trial. The radiologists were the prime focus and were thus interviewed through face-to-face/skype or phone and answered a questionnaire. Study nurses, having more contact with the patient, answered a survey in order to gain additional insights into the patient perspective.   The results show that the radiologists has a positive view towards the administration procedure, which was described as easy and safe. According to the study nurses the patients accept the procedure and they agreed that the patients understand the injection procedure once they received the information. In terms of the emotional state of the patients they were a bit nervous, but they became calmer after receiving the first injection. Based on the above-mentioned findings the intralymphatic injection procedure is described as feasible and has the potential to become a part of the standard clinical routine.

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.