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Diabetes mellitus, environmental and genetic risk factors
Procházková, Iveta ; Hubáček, Jaroslav (advisor) ; Kovacs, Peter (referee)
Diabetes mellitus (DM) is globally widespread group of diseases characterised by increased blood glucose. There are several types, the most common is type 1 DM and type 2 DM. Multifactorial polygenic inheritance is typical for DM with exeption of couple monogenic forms. Type 1 DM is autoimmune form usually manifesting since childhood. Its manifestation is influenced mostly by HLA system genotype, but also by non-HLA genes together with environmental factors, amongst which nutrition of the children is predominant. Type 2 DM develops usually in adulthood. The development is influenced by obesity and lack of movement, but the individual sensitivity to type 2 DM is also genetically determined. Main genetic factors are variations in genes TCF7L2 and FTO as well as in genes coding cyclin dependent kinases.
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Epigenetic regulation of HLA class II genes and their role in autoimmune diseases.
Čepek, Pavel ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Horníková, Lenka (referee)
Abstract Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Its incidence in Europe is continuously rising. The highest T1D risk is associated with HLA (human leukocyte antigen) class II genes. HLA class II molecules play a key role in regulation of immune response. They contribute to the selection of T cell repertoire by presenting antigenic peptides to the CD4+ T lymphocytes. HLA class II expression is controlled by regulatory module that is situated 150 - 300 base pairs upstream of the transcription- initiation site in all HLA class II genes. Polymorphisms in this region are linked to some autoimmune diseases. There were identified several promoter alleles (named QAP) in the HLA DQA1 gene promoter region. Most of the polymorphisms appear to be conserved within haplotype. Individual QAP alleles may have a different promoter strength by which they influence expression of HLA DQA1 gene alleles. Promoter strength can be modulated by DNA methylation. Aims:Our aim was to define methylation profile of HLA DQA1 promoters and determine the mRNA expression of individual alleles of HLA DQA1 gene in T1D patients. The mRNA expression level of HLA DQA1 gene alleles was determined using quantitative PCR. Methods: 30 diabetic pacients (age range 21 to 76 years), were included in this pilot...
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Diagnostic contribution to the evaluation of intervention models in the treatment of type 1 diabetes
Zacharovová, Klára ; Saudek, František (advisor) ; Plecitá, Lydie (referee) ; Mandys, Václav (referee)
During treatment of diabetes mellitus by immunointervention or transplantation, it is necessary to monitor the markers of immune destruction or rejection of surviving insulin producing cells. An aim of this thesis is to improve the possibilities of following autoimmunity and to detect the survival of transplanted pancreatic islet in vivo. Partial aims included vitality testing of isolated islets for transplantation by measurement of respiration activity, observing the process of in vitro labeling of isolated islets with superparamagnetic iron oxide (SPIO) contrast agent for subsequent magnetic resonance imaging (MRI) of islets and observing SPIO particles transport after transplantation. We also studied a new dual paramagnetic contrast agent combined with fluorescein intended for identification of the MRI contrast agent in samples for histology. Further, we assessed autoimmune reaction by evaluation of cytokine response to specific stimulation with auto-antigens. We tried to affect beta-cells destruction by polyclonal anti- thymocyte antibodies in a mouse experimental model. A new method of the islet respiration measurement correlated with other methods of islet quality testing and it was suggested as a diagnostic test before clinical transplantation. Results obtained studying the intercellular...
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Dendritic cells and autoimmune diseases with a view to type 1 diabetes mellitus
Chrástová, Iveta ; Štechová, Kateřina (advisor) ; Krulová, Magdaléna (referee)
Dendritic cells (DC) are professional antigen-presenting cells (APC) that play an essential role in the induction of immune responses. DCs develop from CD34+ hematopoietic stem cells in bone marrow and their role is uptake, processing and presentation of antigens to T cells. DCs can be divided into two distinct subset of cells, myeloid a plasmacytoid DCs. Myeloid DCs (mDC) develop from hematopoietic cells in the presence of GM-CSF and TNF-α or from monocytes in the culture with GM-CSF and IL-4, then with CD40L they mature and produce a large number of IL-12, which is important in driving CD4+ T cell to type Th1. The development of pDC is CD40L and IL-3 dependent and Flt3-L supports this process as well. The essential role of pDC is that they secrete a large amounts of type I IFN in the responses to viruses and so they maintain the antiviral stage. To recognize the viruses pDC express Toll-like receptors 7/9. DCs have on the surface also other groups of receptors, e.g. C-type lectin-like receptors, RIG-I-like receptors and NOD-like receptors. They play the role in the various diseases, mostly autoimmune diseases, in which the immune system recognizes self tissues and activates against them the immune response. Dendritic cells function is that they are competent to activate T cells, in the most cases...
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Development of mortality on diabetes mellitus in developed countries, focusing on the Czech Republic
Koňařík, Martin ; Burcin, Boris (advisor) ; Hulíková Tesárková, Klára (referee)
Development of mortality on diabetes mellitus in developed countries, focusing on the Czech Republic Abstract This thesis addresses the development of diabetes mellitus mortality in selected developed countries between 1950 and 2008 and compares this development with the situation in Czechoslovakia, the Czech Republic respectively. This development is analyzed by sex, age and type of diabetes. Furthermore it also deals with diabetes morbidity and the share of diabetes mortality from the total mortality. The main approach used in this thesis is analysis of standardized mortality rates and this analysis was done both for whole long-term time series and time series within each International Classification of Diseases for individual countries. Based on the results, it was found that the development of diabetes mellitus mortality was similar across selected countries. It could be divided into several phases. Differentiation between mortality rates of males and females that occurred during reference period was so significant that mortality rates of females which were always higher had dropped below the rates of males. This effect is called in this thesis as a transition from higher female mortality to higher male mortality and it occurred in different countries at different times and also had variable-length...
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The diabetic child in kindergarten
VYHLÍDKOVÁ, Anna
The bachelor essay targets on the child specific needs who has diabetes mellitus. It describes how the child disease influences nursery school. The theoretical part informs about profile diabetes, points out unsafe conditions of diabetic and way of result. It helps us to take a look to a psyche of the chronic ill child. Last but not least it attends to a total care about the diabetes child, the specific needs and the demands how the parents, nursery school and the teachers deal with them. The practical part is a case study of the diabetes child in nursery school. It catches the particular situation which points effect of illness out the preschool child, the peer group, nursery school and the family.
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Eating Habits of Type 1 Diabetes Mellitus Patients
KRÁLOVÁ, Kateřina
The topic of my bachelor work is Eating Habits of Type 1 Diabetes Mellitus Patients. The Diabetes mellitus is a chronic illness, which is for its high incidence in the population regarded as disease of civilization. There are approximately 15 000 000 people with diabetes type 1. according to the International Diabetes Federation, which is little over 7 % of the total number of diabetics. The aim of the bachelor work is to describe, through the research, eating habits found at patient type 1 diabetes and to map the reasons that lead to noncompliance of diabetic diet set by physician. So to answer the research questions: "What are the eating habits type 1 diabetic?" and "What are the reasons for patient to not follow recommended diet?" The research part is elaborated in the form of qualitative research using semi-structured interview. Total of seven diabetic patient in the age range from twenty-three to fifty years, provided the interview. The data were obtained from patients who were treated at diabetes physician MD Lenka Dohnalová in the diabetes clinic at a hospital in České Budějovice. Interviewing these patients was not purposely carried out in the presence of nurses or diabetologist in order to prevent degradation of the answers of interviewed persons. As result, the respondents were not afraid to tell the truth and the information obtained was as objective as possible. Patients were helpful and willing to give interviews. Respondents did not mention their names so the entire interview is anonymous. Everyone agreed to provide an interview and also agreed on being recorded. Two research questions were set and answered on the basis of anonymous interviews. Research Question No. 1: 1st What are the eating habits of type 1 diabetes patients? It is obvious that patients with diabetes were told that they should keep track of the number of carbohydrates eaten in the food. Six respondents use replaceable units to achieve it, 12 grams of carbohydrate equals 1 replaceable unit. One respondent does not recalculate the carbohydrates in the food on replaceable units, but is familiar with using the grams of carbohydrates. I was surprised by the answer on the special diet, a product formerly known as "dia," I did not expect that it consumes only one respondent. Beyond my original expectations is also surprising fact that neither of the respondents check the glycemic index in their food. Research Question No. 2: 2nd What are the reasons not to comply the recommended diet? It is obvious that patients try to comply the regime. None of the respondents currently have a problem with self-monitoring, application of insulin or consumption of food and beverages at school or at work. One respondent stated that she had these problems at work, and she is now on a disability pension. The results of the research are useful for health professionals who take care of diabetic patients. Intended use of the work in practice: Issuing this in diabetes clinics should support and enhance awareness of patients with diabetes about their disease.
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Selfmonitoring of Type 1 Diabetes mellitus in adolescents
KORELOVÁ, Andrea
Type 1 diabetes mellitus is a chronic, lifelong disease. The younger the patient, the more seriously the disease affects his (her) childhood. The disease brings about a lot of changes, it involves the loss of freedom and independence. Diabetes makes the normal troubles of adolescence even more difficult. Adolescence is a hard stage of life for patients with the type 1 diabetes mellitus because it is a period when the compensation of diabetes is more difficult than in the previous and following stages of life. Regular self-monitoring is one of the crucial tasks. The selfmonitoring is important for the overall compensation of diabetes and also for the clinical results of treatment. Self-monitoring is the process of monitoring and measurement of one´s own glycemia and ketones in blood and sugar and ketones in urine. It enables the diabetic patient a better orientation in the disease and a certain level of independence. Self-monitoring helps parents gain confidence in cure of their children suffering from diabetes. The theoretical part of my thesis deals with the questions of the type 1 diabetes mellitus and the method of self-monitoring. The objective of the practical part was to survey the subjective view of adolescents with the type 1 diabetes mellitus on self-monitoring and the level of their self-reliance. I set hypotheses suggesting that adolescents perceive self-monitoring to be uncomfortable and cannot cope with the procedures independently. These hypotheses were not confirmed in my research. To get relevant data, I used the questionnaire method. I handed out questionnaires to young patients with diabetes aged 13{--}18 years. A letter for patients´ parents asking for their written consent with the research was attached to the questionnaire.
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