Diabetic nephropathy is a chronic kidney disease and one of the more severe complications from diabetes mellitus type 2. The glomerular and tubular dysfunctions usually lead to end stage renal disease and the treatments of these patients (dialysis, kidney transplants) are a huge economic burden for the society. Due to an epidemiologic increase of type 2 diabetes, conventional diagnostic markers like creatinine and albumin are not sufficient, since they are only able to identify already existing kidney damage. With targeted metabolomics, the analysis of small molecules produced from metabolism, this project aimed at finding novel and more sensitive metabolic biomarkers from several different classes of metabolites. The different assays were performed with flow injection analysis, high performance liquid chromatography, gas chromatography and mass spectrometry, and with principal component analysis and discriminant analysis, up-and down-regulated metabolites could be identified and their respective biochemical pathways, if possible, explained. In diabetics significantly elevated concentrations of very long chain fatty acids (impaired peroxisomal β-oxidation), urinary sugars and acylcarnitines in plasma could be recognized. Markers indicating kidney damage included significantly increased plasma concentrations of asymmetric dimethylarginine (inhibition of nitric oxide synthase resulting in decreased endothelial functionality) and histamine (indication of uremic pruritus). Oxidative stress was also found to be a potential prognostic marker as indicated by the raised methionine-sulfoxide to methionine ratio in nephrotic patients. To summarize, this project succeeded in identifying metabolic biomarkers both for diabetes type 2 and nephropathy, which in the future might become important tools in slowing down progression or diagnosing these diseases.

I Sverige är 365 000 personer drabbade av sjukdomen diabetes mellitus typ 2. Sjukdomen kan bero på ärftliga eller miljömässiga faktorer. Sjukdomen börjar med insulinresistens i muskler, lever och fettvävnad som kan leda till allvarliga komplikationer. Patienter har behov av stöd från sjukvårdspersonalen för att hantera de egenkontroller och livsstilsförändringar som är nödvändiga. Genom empowerment kan patienter ta kontroll över sjukdomen. Litteraturstudiens syfte var att undersöka hur patienter med diabetes mellitus typ 2 beskriver sitt behov av stöd. Litteraturstudien består av 10 vetenskapliga artiklar, sex kvalitativa, två kvantitativa och två artiklar som är både kvalitativa och kvantitativa. Resultatet redovisas i fem teman: patientens behov av information som stöd, patientens behov av kunskap som stöd, patientens behov av undervisning som stöd, patientens behov av socialt stöd, patientens behov av stöd från sjukvårdspersonal. Patienter önskar information om blodsockerkontroller, medicinering, kost och motion från sjukvårdspersonalen för att kunna genomföra egenvård. Utbildning i grupp uppskattades av patienter, särskilt tillsammans med patienter med samma sjukdom och erfarenheter som de själva. Stöd från patientens omgivning kan stärka patientens livskvalitet. Upplevs behovet av stöd från sjukvårdspersonalen som tillräckligt upplevs sjukdomen hanterbar av patienterna. Det är därför relevant att sjuksköterskeprogrammet lyfter fram behov av stöd för patienter med diabetes mellitus typ 2 redan i utbildningen. Blivande sjuksköterskor kan då överföra kunskapen till vårdverksamheten. För vidare forskning inom ämnet vore det intressant att fler studier i Sverige undersöker patienternas behov av stöd och hur de upplever att deras behov blir bemötta i dagens sjukvård. / There are 365 000 people in Sweden who suffer from diabetes mellitus type 2. The disease is caused by factors that are genetic or environmental. The disease occurs from insulin resistance in the cells of the muscle, liver or fat tissue. The disease can result in serious complications. The patient has a need for support from the healthcare professionals to be able to manage self-management and the life- style changes that are necessary. The patient can through empowerment take charge over the disease. The aim of this study was to define how patients who suffer from diabetes mellitus type 2 describe their need for support. The literature study consists of ten scientific articles, six qualitative, two quantitative and two articles that were both qualitative and quantitative. The result is presented as five themes: the patient’s need for information as support, the patient’s need for knowledge as support, the patient’s need for education as support, the patient’s need for social support, the patient’s need for support from healthcare professionals. The patients desired information from the healthcare professionals about self- monitoring of blood glucose, medications, diets and exercise to be able to perform self-management. Peer education was appreciated by patients, particularly with patients with the same disease and experience as their own. The support from the surroundings could strengthen patient’s quality of life. If the need for support from the healthcare professionals was experienced as adequate the disease seemed more manageable by the patients. Therefore it is relevant, already in the beginning of the nursing program, to emphasize the need for support with diabetes mellitus type 2. Registered nurses can then include the knowledge within the clinic. Further research within healthcare is recommended, especially studies within Sweden that investigate the patient’s need for support.

<p>Diabetic nephropathy is a chronic kidney disease and one of the more severe complications from diabetes mellitus type 2. The glomerular and tubular dysfunctions usually lead to end stage renal disease and the treatments of these patients (dialysis, kidney transplants) are a huge economic burden for the society. Due to an epidemiologic increase of type 2 diabetes, conventional diagnostic markers like creatinine and albumin are not sufficient, since they are only able to identify already existing kidney damage. With targeted metabolomics, the analysis of small molecules produced from metabolism, this project aimed at finding novel and more sensitive metabolic biomarkers from several different classes of metabolites. The different assays were performed with flow injection analysis, high performance liquid chromatography, gas chromatography and mass spectrometry, and with principal component analysis and discriminant analysis, up-and down-regulated metabolites could be identified and their respective biochemical pathways, if possible, explained. In diabetics significantly elevated concentrations of very long chain fatty acids (impaired peroxisomal β-oxidation), urinary sugars and acylcarnitines in plasma could be recognized. Markers indicating kidney damage included significantly increased plasma concentrations of asymmetric dimethylarginine (inhibition of nitric oxide synthase resulting in decreased endothelial functionality) and histamine (indication of uremic pruritus). Oxidative stress was also found to be a potential prognostic marker as indicated by the raised methionine-sulfoxide to methionine ratio in nephrotic patients. To summarize, this project succeeded in identifying metabolic biomarkers both for diabetes type 2 and nephropathy, which in the future might become important tools in slowing down progression or diagnosing these diseases.</p>

The aim of the present thesis was to assess the occurrence of early lower extremity arterial disease (LEAD) in patients with diabetes and to assess novel potential risk markers for development or worsening of LEAD in the same patients. In parallel different measures of impaired peripheral circulation were evaluated. The measurement of ankle-to- brachial blood pressure index (ABI) to screen for asymptomatic LEAD in diabetic subjects is unreliable since a large proportion of patients have stiff ankle arteries (mediasclerosis) and thus may display a too high ABI. We studied type 1-, type 2 diabetic and non-diabetic subjects without a previous history of LEAD and a composite variable of ankle – plus toe blood pressures and indices was compared to ABI alone in detecting LEAD. Significantly more subjects with reduced peripheral circulation were detected using the composite variable compared to ABI alone. This was particularly true in diabetic subjects, about 30% of whom had signs of impaired peripheral circulation. Thus, it was found that toe blood pressure measurements, alone or in combination with ankle blood pressure measurements, increase the sensitivity for finding early asymptomatic LEAD in diabetic subjects. No significant difference in reproducibility between measurements of absolute ankle- and toe blood pressure and indices was found, but a correlation between systemic (brachial) and toe blood pressure variations over time may suggest that indices are more correct in assessing peripheral arterial circulation. Furthermore, toe blood pressure measurements can be performed using either the great toe or dig II and a strong concordance is found between these measurements. In addition, since the pole-test, another non-invasive method to measure peripheral blood pressure which is less sensitive to the presence of mediasclerosis compared to ABI, correlated significantly with toe blood pressure measurements this method may be used as an alternative screening method in subjects with previously known LEAD. Age, hypertension and glycemic control are well known risk factors and, in addition, high tissue plasminogen activator (tPA) activity turned out to be a novel early marker for asymptomatic LEAD in diabetic subjects, particularly in patients with type 2 diabetes. Age and hyperglycemia are the most important risk factors for development and progression of subclinical lower extremity arterial disease in type 2 diabetic subjects. No independent associations between markers of inflammation, such as CRP, interleukin-6 and TNF-α and early asymptomatic LEAD were seen among non-diabetic or diabetic subjects. In conclusion, impaired arterial circulation in the lower extremities is common in diabetic subjects even in the absence of symptoms. Including toe blood pressure measurement when screening for asymptomatic LEAD in diabetic subjects improves the ability to detect reduced peripheral circulation and this method avoids falsely elevated blood pressures readings due to mediasclerosis in the ankle arteries. Moreover, an altered fibrinolytic activity should be further evaluated as an early marker of atherosclerosis and LEAD.

This diploma thesis is focused on the knowledge of patients suffering from type 2 diabetes mellitus. The main aim of this work is to determine how well these patients are educated about type 2 diabetes mellitus depending on both the duration of the disease and whether they attend a nutritional therapist. The work is divided into a theoretical and a practical part. The theoretical part provides general information about diabetes mellitus. There is a marginal description of pancreatic function and the history, definition and classification of diabetes mellitus. Type 2 diabetes mellitus, its pathogenesis, clinical picture, diagnosis, screening, therapy and associated complications, both acute and chronic, are discussed in more detail. As part of type 2 diabetes therapy there is the most discussed non-pharmacological treatment, which includes dietary measures and physical activity. The practical part was formulated on the basis of quantitative research, which was carried out using a questionnaire survey. Data were collected from November 2019 to March 2020. 150 questionnaires were distributed to different inpatient departments and clinics in Jičín Hospital. 106 completed questionnaires were returned, but 24 of them had to be rejected due to incomplete or incorrect completion. The research sample...

Accessibility of health care in the Czech Republic according to the geodemographic characteristics of the population Abstract Public healthcare is a subject that affects us all. The health and medical status of the population is a key measure of how advanced a country is. That is why healthcare issues attract so much debate. A number of factors affect the health of a nation. On one hand there are factors such as how individuals look after their health. Dietary habits, sufficient physical exercise and preventive care are all factors that the individual has control over. On the other hand, however, there are determinants affecting whether healthcare take-up is adequate. The cost of providing healthcare and medical equipment together with healthcare accessibility - the topic of this thesis - are factors affecting the population's health. It is the duty of all public healthcare stakeholders to limit the impact of these determiners. One of the main barriers to healthcare take-up is accessibility. On 1 January 2013 government decree no. 307/2012 Coll. came into effect quantifying healthcare accessibility for the first time. This law stipulates the local and travel time accessibility that ensures accessibility depending on type of healthcare on the basis of an upper travel time limit or waiting period....

Insulin pump treatment (CSII) is considered the most physiological way to imitate the healthy body’s insulin profile in adolescents with diabetes. However, despite the use of CSII, achieving the recommended disease control is difficult for adolescents. The aim of this thesis was to explore aspects of self-management of diabetes in adolescents using insulin pumps in order to describe conditions contributing to the recommended disease control. Three methods of bolusing (normal, dual-wave and square-wave) in connection with pasta meals were tested in a crossover study among 15 adolescents with diabetes to assess whether one method was superior in managing glucose levels. A cross-sectional study among 90 adolescents being treated with CSII was conducted to investigate the management of CSII, including the administration of bolus doses. Two qualitative interview studies, based on the grounded theory method, were performed to gain insight into the processes involved in taking bolus doses and to investigate reasons for missed bolus doses and strategies for avoiding missing them. Twelve adolescents, four parents and one diabetes specialist nurse were interviewed. No method of bolusing was found to be superior in managing the glucose levels after these meals. The post-prandial glucose peaks were &lt;10 mmol/L, in 48% of the cases, regardless of bolus methods. This indicates that adolescents can be encouraged to individually test which bolus method gives them the most normal post-prandial glucose levels. The cross-sectional study showed that adolescents were satisfied with CSII, but that 38% had missed more than 15% of the bolus doses the day under study. The frequency of bolus doses correlated with the disease control. Findings from the interview study revealed the need to clarify the responsibility for diabetes self-management in continuous negotiation between adolescents and parents to avoid insulin omission. The main reason for missed boluses was lost focus, and the strategies for remembering them were agreements involving reminders. The thesis describes that individual dose testing, clarification of responsibility and agreements involving reminders are conditions contributing to the recommended disease control. The thesis also describes that lost focus and a lack of responsibility can lead to insulin omission and be a hindrance to achieving disease control. / Anna Kernell avled maj 2010.

Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.