Bakgrund: Diabetes typ 2 är en kronisk folksjukdom världen över. Egenvård är en essentiell del av behandlingen vid diabetes typ 2, om den missköts riskerar patienten att drabbas av allvarliga komplikationer. Sjuksköterskan har ett ansvar att säkerställa att patienten har rätt kompetens för att uppnå en god och långsiktig följsamhet vid egenvård. Syfte: Syftet var att belysa patienters upplevelser av hinder och möjligheter till egenvård vid diabetes typ 2. Metod: Studien var en allmän litteraturstudie med induktiv ansats. Resultat: Fyra kategorier identifierades: kunskapens betydelse för egenvård, levnadsvanors påverkan på egenvård, social, kulturell och ekonomisk påverkan på egenvård samt motivationens betydelse för egenvård. Konklusion/implikation: Patienter upplever både hinder och möjligheter till egenvård vid diabetes typ 2. Kunskapsbrist, svårigheter att ändra etablerade levnadsvanor, dyr hälsosam mat, dyra sjukvårdsbesök och dyra diabetesläkemedel är hinder till egenvård. Familjens påverkan på egenvård kan vara både hindrande och främjande. Individuellt anpassad patientutbildning rekommenderas för att rusta patienter med den kunskap som krävs vid egenvård av diabetes typ 2. Utökad forskning gällande vuxna patienters upplevelse av egenvård inom Skandinavien rekommenderas. / Background: Type 2 Diabetes is a chronic public health disease worldwide. Self-management is an essential part of treatment. Patients with poor adherence to self-management are at risk of developing serious complications. Nurses have a responsibility to ensure that patients have proper competence to achieve good and long-term adherence to self-management. Aim: This study aimed to illustrate patients' experiences of barriers and facilitators to self-management in type 2 diabetes. Method: This study was a general literature review with an inductive approach. Results: Four categories were identified: the importance of knowledge for self-management, the influence of lifestyle on self-management, social, cultural and economic influence on self-management as well as the importance of motivation for self-management. Conclusion/Implication: There are both barriers and facilitators for patients with type 2 diabetes to engaging in self-management. Lack of knowledge, difficulties in changing established lifestyles as well as high cost of healthy food, healthcare visits and diabetes medications serve as barriers to self-management. Family influence on self-management can be both inhibiting and facilitating. Individually tailored patient education is recommended to equip patients with the knowledge required for self-management of type 2 diabetes. More research regarding adult patients’ experience of self-management within Scandinavia is recommended.

BACKGROUND: Type 2 diabetes (T2DM) is a metabolic disease that arises from insulin resistance and facilitates progression to cardiovascular consequences including myocardial infarction, coronary artery disease, and stroke. A contributor to the cardiovascular complications seen in T2DM is endothelial dysfunction. From a molecular standpoint, studies have shown that the pathophysiology of T2DM involves an altered metabolic milieu and increased oxidative stress, which both arise from insulin resistance, and lead to endothelial dysfunction. There is still much to discover on the pathways that are altered in this disease. Proteomics is a rapidly improving technique that can elucidate the differences in serum biomarkers, and their relationship to vascular endothelial health to further understand the pathophysiology of T2DM. OBJECTIVE: To evaluate the proteomic background and the implicated pathways in T2DM, and to understand how these biomarkers are associated with endothelial cell phenotype and systemic vascular function. METHODS: Age and sex similar individuals with T2DM and control individuals without T2DM between the ages of 30 and 80 were enrolled in this study. Blood was obtained for blood glucose and insulin levels and two proteomics panels assessing 192 serum biomarkers. Baseline vascular measures were obtained including blood pressure, heart rate, and flow-mediated dilation. Endothelial cells collected from participants were stimulated with insulin ex vivo and stained with phosphorylated endothelial nitric oxide synthase (p-eNOS) to measure changes in the insulin-mediated eNOS pathway. Associations between biomarker levels and insulin-stimulated p-eNOS levels were evaluated. RESULTS: The present study includes 69 subjects including 37 subjects with T2DM (age 57±8 years, 41% female) and 32 control subjects (age 53±9 years, 38% female). Measures of vascular health showed evidence of impairment in patients with T2DM including higher pulse pressure (56±12 mmHg versus 48±11 mmHg, p=0.02) and lower flow-mediated dilation (6.04±3.41% versus 9.1±4.4%, p=0.01). The proteomic panels revealed 24 serum biomarkers that were significantly upregulated and 2 that were significantly downregulated (adjusted p<0.05) in patients with T2DM compared to nondiabetic controls. These biomarkers are mainly involved in metabolism, vascular and fluid homeostasis, immune response, and apoptosis. Endothelial cell phenotype was abnormal in patients with T2DM compared to controls: mean fold change in insulin-stimulated p-eNOS was 0.34±0.07 for nondiabetic controls and -0.14±0.03 (p=0.01) for patients with T2DM. Renin and Adrenomedullin were significantly associated with lower insulin stimulated p-eNOS activation (r=-0.38, r=-0.27, and p=0.004, p=0.049 respectively). Whereas Chymotrypsin C (r=0.37, p=0.006), Paraoxonase 3 (r=0.35, p=0.009), Lipoprotein Lipase (r=0.34, p=0.01), and Superoxide Dismutase 2 (r=0.31, p=0.02) were significantly associated with higher insulin stimulated p-eNOS activation. CONCLUSIONS: We found associations between serum biomarker levels and insulin-stimulated p-eNOS levels which showed that there is a relationship between altered biomarkers and endothelial cell phenotype. Patients with T2DM had worse vascular endothelial health as shown by measures of endothelial dysfunction and arterial stiffness. Endothelial cell insulin resistance was present in patients with T2DM. In the same group, serum biomarkers showed elevated adiposity, inflammation and oxidative stress, and upregulation of the renin-angiotensin-aldosterone system.

Prediabetes is defined by elevated blood glucose concentrations not high enough to meet criteria for type 2 diabetes. Exercise or metformin, a common “anti-diabetes” medication, may attenuate the progression from prediabetes to type 2 diabetes by improving insulin sensitivity and cardio-metabolic health. Because each treatment has its primary action in different tissues, combining exercise (muscle) with metformin (liver) may further enhance insulin sensitivity and cardio-metabolic health. Purpose: To determine the efficacy of combining exercise training with metformin on insulin sensitivity and cardio-metabolic health in men and women with prediabetes. We hypothesized that the combined treatment would improve insulin sensitivity and cardio-metabolic health more than either treatment alone. Methods: Thirty-two men and women with prediabetes were placed in placebo (P), metformin (M), exercise training and placebo (EP), or exercise training and metformin (EM) groups. Pill distribution was double-blind, and the groups were well-matched for age, weight, and fitness. There were no baseline differences in any characteristic. Subjects were provided P or 2000mg/d of M for 12 weeks and EM and EP underwent a progressive training protocol. Insulin sensitivity was measured 28-30hr post-exercise with a euglycemic hyperinsulinemic clamp. Traditional cardio-metabolic measures were also collected in the fasted state (e.g. blood pressure, blood lipids and inflammation). Group means were compared using a 2-way repeated measures analysis of variance. Results: Relative to baseline, all 3 interventions increased insulin sensitivity (p < 0.05), however, EP increased insulin sensitivity approximately 25-30% more than either EM or M. Compared to control, EP and M both lowered systolic blood pressure and C-reactive protein (p < 0.05, p = 0.06) and these reductions were approximately 15% more than EM. Each treatment raised HDL (p < 0.05). Enhanced insulin sensitivity was associated with increased non-oxidative glucose metabolism (i.e. glucose storage) (r = 0.85; p < 0.01). Conclusions: Despite more weight loss (4 kg), metformin blunted, rather than accentuated the effects of training on enhancing insulin sensitivity and lowering systolic blood pressure and inflammation. Given that metformin and physical activity are widely recommended treatments for prediabetes, it is important to better understand the mechanisms and ramifications of the combined treatment.

Background: Type 2 diabetes affects approximately 8% of the world’s population. Individuals of South Asian ancestry tend to develop metabolic abnormalities, leading to diabetes, at lower measures of absolute obesity and approximately 10 years earlier than white Caucasians. Current literature is unclear on the source of this ethnic heterogeneity; the variation in risk cannot be explained by lifestyle factors alone. The overarching aim of this thesis is to explore the role of genetic variants and epigenetic differences to explain the greater risk for type 2 diabetes among South Asians. Methods: We first conducted a systematic review of the literature to ascertain the genetic risk from known single nucleotide polymorphisms (SNPs) among South Asians. We then compared these risk estimates to those from white Caucasians in a cohort of 69,033 individuals. Second, using the EpiDREAM prospective cohort study of individuals at high-risk for diabetes, we assessed the impact of genetic burden for impaired pancreatic beta-cell function alone and together with abdominal obesity on glucose traits. Ethnic heterogeneity in this interaction was also studied. Lastly, using data from two Canadian birth cohorts of South Asian and white Caucasian ancestry, we investigated ethnic differences in the epigenetic architecture for genes known to be implicated birth weight and length, as both are associated with the future risk of adult diabetes. Results: The systematic review identified 15 SNPs robustly associated with type 2 diabetes in both South Asians and white Caucasians. The magnitude of risk and allele frequency of these genetic variants did not differ between the ethnic groups. Additionally, we identified 8 novel polymorphisms implicated in diabetes only among South Asians. Second, using data from the EpiDREAM study, we identified an interaction between cumulative genetic burden of beta-cell impairment, measured using an un-weighted genotype score, and abdominal obesity on glucose traits in South Asians, but not white Caucasians. Third, our investigation of differential DNA methylation between the ethnic groups revealed seven CpG sites for which changes in methylation corresponded to alterations in birth weight among white Caucasians, but not South Asians. An independent agnostic genome-wide search identified methylation levels at three CpG sites that appear to uniquely modulate birth weight in South Asians. Conclusions: Overall, our results indicate that the greater risk for metabolic traits in South Asians likely does not result from common genetic variants shared by both South Asians and white Caucasians. Rather, differences in risk may be additionally influenced by unique risk variants in South Asians. Furthermore, it appears that the risk from a genetic impairment in South Asians may be magnified by abdominal obesity. / Thesis / Doctor of Philosophy (PhD)

Type 2 diabetes mellitus (T2DM) disproportionality affects under-represented groups, specifically Asian Americans. Asian Americans are less likely to receive proper diabetes mellitus screening compared to other racial and ethnic groups, potentially due to improper screening guidelines by clinicians, and Asian Americans being unaware of their increased risk for diabetes mellitus. There are differences in the etiology of T2DM in Asian Americans compared to White Americans. Due to the increasing rates of T2DM among Asian Americans, new approaches in the screening of T2DM should be tailored based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is insufficient to properly evaluate adiposity in Asian-American adults due to Asian Americans having a lower BMI with a higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) may be better for screening Asian Americans for T2DM. Multiple modifiable risk factors, such as sedentary behavior, and dietary intake (specifically dietary magnesium intake) can increase the risk for T2DM. Lack of physical activity can result in insulin resistance and impaired glucose metabolism as a result of muscle disuse and decreased lean body mass. Half of the Asian-American population is not consuming the recommended amounts of magnesium from foods, drinks, and dietary supplements. There is an inverse relationship between increased dietary magnesium intake and the risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The overarching goal of the present study was to establish which independent variables (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian-American adults using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. The present study also evaluated the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the NHANES data from 2011 to 2020. / Doctor of Philosophy / Asian Americans have been disproportionately affected by type 2 diabetes mellitus (T2DM). Compared to other racial and ethnic groups, Asian Americans are less likely to receive proper diabetes mellitus screening. This may be due to inadequate screening guidelines and lack of awareness about their increased risk for diabetes mellitus. The cause of T2DM in Asian Americans differs from that in White Americans, which calls for tailored screening approaches based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is not enough to accurately assess body fat in Asian-American adults, because they tend to have a lower BMI, but higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) might be more suitable for screening Asian Americans for T2DM. Several modifiable risk factors, such as a sedentary lifestyle and dietary intake (specifically, dietary magnesium intake), can increase the risk of T2DM. Lack of physical activity can lead to insulin resistance and impaired glucose metabolism due to muscle disuse and reduced lean body mass. Half of the Asian-American population does not consume the recommended amounts of magnesium from food, drinks, and dietary supplements. Researchers have shown that increased dietary magnesium intake is linked to a reduced risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The main goal of this study was to identify which factors (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian Americans. This was completed using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. Additionally, the study aimed to establish the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the same NHANES data.

Introduction: Gestational diabetes mellitus (GDM) is a metabolic disorder that has been defined as glucose intolerance that is first identified during pregnancy. The etiology of GDM is not yet fully understood, but there are several risk factors that appear to contribute to its development such as advanced age at pregnancy, family history of type 2 diabetes mellitus, and a previous history of GDM. The discovery of predictive GDM biomarkers has the potential to enable early GDM detection and lead to earlier diagnosis and preventative interventions. Objective: Perform metabolomics analysis on plasma samples collected at pre-conception and at 26-weeks gestation to investigate metabolic differences between participants of the gestational diabetes prevention (GDP) clinical trial who developed GDM and those who did not. Methods: Targeted metabolomics, comprised of primary metabolomics, biogenic amines, and lipidomics assays, was performed using UPLC-MS on plasma samples collected from a subset of 30 participants that completed the GDP study at preconception and 26 weeks gestation. The samples used for this analysis were from participants who developed GDM (n=19) and those who did not (n=11) in their pregnancy following their participation in the GDP study. Results: Multivariate analysis revealed indoxyl sulfate as significantly higher in the GDM group at both preconception and at 26 weeks gestation (VIP scores > 2.9). Preconception samples collected at the end of the GDP intervention study PC 38:0 was higher in the GDM group versus the non-GDM group (p < 0.05) whereas thymidine was lower in the GDM group (p < 0.05), in addition to numerous cell membrane lipids (VIP > 2.0). At 26 weeks gestation, D-glucuronic acid was higher in the GDM group versus the non-GDM group (p < 0.03), while LPE 22:6, SM 18:1 (22:4), PE 38:6, PE 40:6, PE 40:7, and PE (O-38:0) were lower in the GDM group (p < 0.04), in addition to numerous cell membrane lipids (VIP > 2.0). Discussion: The differences observed between the GDM and non-GDM groups at the two plasma collection time points may suggest metabolic alterations associated with GDM-induced metabolic dysregulation. These findings may help direct future research to focus on changes in lipid metabolism during pre-pregnancy for possible biomarkers of GDM. Repeat studies with diverse cohorts are needed to help identify a panel of metabolites that may serve as early biomarkers of GDM.

Bakgrund: Diabetes typ 2 är den vanligaste formen av diabetes. Cirka 5 procent av Sveriges vuxna befolkning hade diabetes år 2018. Diabetes typ 2 kräver omfattande livsstil förändring och egenvårdinsats. Många personer med sjukdomen ser sin livskvalité minska drastiskt med tiden. Komplikationer som kan följa sjukdomen och de förebyggande insatser från sjukvården innebär betydande direkta och indirekta kostnader för samhället. Sjukdomen är till stor del livsstilsrelaterad och orsakas bland annat av fysisk inaktivitet och ohälsosamma kostvanor även om ärftligheten också spelar stor roll. Den rekommenderade förändringen vid ohälsosamma levnadsvanor kräver en stor insats av egenvård från individen själv och stöd från omgivningen och hälso- och sjukvården. Syfte: Syftet var att beskriva personers upplevelser av hinder för att utföra egenvård vid Diabetes typ 2. Metod: En litteraturöversikt baserad på vetenskapliga artiklar med kvalitativ design Resultat: Resultaten i denna studie identifierade faktorer som påverkar egenvårdsförmågan hos personer som har Diabetes typ 2. Faktorerna som identifierades var individers motivation och förmåga, stöd från ens familj och vänner, materiella förutsättningar och ekonomiska förhållanden, närvaron av en stödjande infrastruktur i hälso- och sjukvården och rådande kulturella normer. Sammanfattning: För att förbättra egenvården bör huvudfokus vara att förändra individens kunskap, attityder och beteende. Detta kan uppnås genom egenvårdsutbildning, kontinuitet i den kliniska vården, personligt stöd och utveckling av hälsosystem. Det är också viktigt att utbilda vårdpersonal så att de kan effektivt stödja egenvårdsinsatser. / Background: Type 2 diabetes is the most common form of diabetes. Approximately 5 percent of Sweden's adult population had diabetes in 2018. Type 2 diabetes requires extensive lifestyle changes and self-care efforts. Many people with the disease see their quality of life decrease drastically over time. Complications that may follow the disease and the preventive measures from healthcare involve significant direct and indirect costs to society. The disease is largely lifestyle-related and is caused by, among other things, physical inactivity and unhealthy eating habits, although heredity also plays a major role. The recommended change in unhealthy living habits requires a great deal of self-care from the individual and support from the environment and health care. Aim: The aim of this study was to describe people's experiences of obstacles to performing self-care in type 2 diabetes. Method: A literature review based on scientific articles with qualitative design Resultat: The results of this study identified factors that affect the self-care ability of people with type 2 diabetes. The factors identified were individuals' motivation and ability, support from one's family and friends, financial conditions, the presence of a supportive health care infrastructure and prevailing cultural norms. Summary: To improve self-care, the main focus should be on changing the individual's knowledge, attitudes and behavior. This can be achieved through self-care education, continuity in clinical care, personal support and development of health systems. It is also important to train healthcare professionals so that they can effectively support self-care initiatives.

Bakgrund: Den kroniska sjukdomen typ 2 diabetes är en sjukdom äldre och yngre insjuknar i och där allvarliga konsekvenser och höga kostnader för samhället medföljer. För att minska framtida komplikationer hjälper det att ta till sig egenvård och detta är möjligt med hjälp av en sjuksköterska. Sjuksköterskans roll är viktig för att uppmuntra den enskilde individen till delaktighet i sin vård och viljan att främja hälsan.       Syfte: Syftet med denna litteraturöversikt är att beskriva sjuksköterskans upplevelse av egenvården hos patienter med typ 2 diabetes.      Metod: Den valda metoden är litteraturöversikt som har utförts enligt Friberg. CINAHL Complete och PubMed är databaser som har använts i sökningen där tio vetenskapliga artiklar valdes för att användas till resultatet och identifikationen av teman.      Resultat: Tre huvudteman har identifierats i resultatet: Upplevelsen av kommunikation, Upplevelsen av kunskapens betydelse och Upplevelsen av kulturella utmaningar och andliga övertygelser.      Sammanfattning: Litteraturöversiktens resultat visade kommunikationen och kunskapens vikt men även de kulturella utmaningarna. Att kommunicera och utbilda är viktigt för att stödja egenvård och kunna utbilda. Vid kommunikations- och kunskapsbrist så upplevde sjuksköterskorna saknad av motivation och vilja att förstå bland patienter. Med de kulturella utmaningarna påvisade resultatet att religiösa och andliga övertygelse föredras i vissa kulturer. Men även att diabetes typ 2 är tabubelagd och stigmatiserad, vilket i sin tur påverkar patientens vilja att tillta kunskap och hjälp av sjuksköterskan. / Background: The chronic disease type 2 diabetes is a disease that affects older people and younger people, with serious consequences and high costs for society. To reduce future complications, it helps to adopt self-care which is possible with the help of a nurse. The nurse's role is important in encouraging the individual to participate in their care and the desire to promote health.      Aim: The purpose of this literature review is to describe the nurses’ experience of self-management in patients with type 2 diabetes.      Method: The chosen method is a literature review that has been carried out according to Friberg. CINAHL Complete and PubMed are databases that have been used in the search where ten scientific articles were selected for use in the results and the identification of themes.      Results: Three main themes have been identified in the results: The experience of the importance of communication, The experience of the importance of knowledge and The experience of cultural challenges and spiritual beliefs.      Summary: The results of the literature review showed the importance of communication and knowledge but also the cultural challenges. Communicating and educating is important to support self-care and be able to educate. In the event of a lack of communication and knowledge, the nurses experienced a lack of motivation and willingness to understand among patients. With the cultural challenges, the results showed that religious and spiritual beliefs are preferred in some cultures. But also that type 2 diabetes is taboo and stigmatized, which in turn affects the patient's willingness to gain knowledge and help from the nurse.

Background: Type 2 Diabetes (T2D) is growing in prevalence worldwide over the last century. T2D incidence is linked to numerous complications, increased risk of heart disease, and oncology outcomes. This highlights the importance of preventive measures for T2D, wherein genetic predisposition can serve as an early warning sign. The role of rare variants (RVs) in T2D pathogenesis has not been adequately explored due to study size limitations, therefore we hypothesized that new associations could be found using publicly available data repositories. Methods: Significant RV gene burden for T2D risk was discovered using exome sequences obtained from the United Kingdom Biobank (UKB) (n=162,215), then tested for replication in the Korean Association Resource project (n=973), the Metabolic Syndrome in Men Study (n=969), the San Antonio Mexican American Family Studies (n=309), and a pooled meta-analysis of the latter three cohorts. RV gene burden was reassessed in secondary analyses using T2D cases from each cohort and summary level data from the Genome Aggregation Database (GnomAD) (n=125,748). Results: UKB exome wide significant associations were found in GCK (OR=2.44, p=8.91×10-11) and PAM (OR=1.32, p=1.39×10-6), and suggestive associations (p<0.001) were found in 33 additional genes. Replication was limited in KARE, METSIM, SAMAFS and in the secondary analyses with GnomAD because of limited sample sizes and miscalibration with the external control, respectively. Follow-up analyses include exploration of RV gene burden in additional diabetes subtypes, evaluation of clinical features between RV carriers and non-carriers, comparing the ability to predict T2D with rare variant, polygenic, and phenotypic risk scores. Methodological improvements include the incorporation of robust analytic tools and increasing access to a greater diversity and number of samples. Conclusion: Publicly available exome sequencing data has identified genes where RV burden affects T2D pathogenesis and risk. The study of rare genetic variation in diabetes is just beginning. / Thesis / Master of Science (MSc)

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