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Insulin Resistance and Metabolic inFlexibility : the Influence of Renin Angiotensin System Inhibition
Wohl, Petr ; Pelikánová, Terezie (advisor) ; Prázný, Martin (referee) ; Vondra, Karel (referee)
Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...
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Relationship of oxidative stress to parameters of diabetes control in development of vascular complications.
Pelcl, Tomáš ; Prázný, Martin (advisor) ; Rušavý, Zdeněk (referee) ; Šmahelová, Alena (referee)
The aim of this thesis is to contribute to the clarification of the pathogenesis of chronic complications of diabetes mellitus. The main goal of the research was glycaemic variability, its contribution to the activation of oxidative stress and its possible role in the process of advanced glycation, all beyond the scope of persistent hyperglycaemia itself. Another aim of the work is to contribute to the clarification of a possible relationship between glycaemic variability and vascular complications of diabetes. We were the first to describe the association between the concentrations of reactive aldehydes formed during lipid peroxidation and disorders of skin microvascular reactivity in patients with type 1 diabetes (DM1). Elevated markers of oxidative stress were found in this group, furthermore during the 3 years of follow-up higher plasma antioxidant activity was observed. These findings were not dependent of the method of glucose monitoring and glucose variability, which was lower in a subgroup of patients using real-time continuous glucose monitoring (rt-CGM), compared to a subgroup using conventional glucometers. However, it is clear, that hyperglycaemia alone induces increased oxidative stress in patients with diabetes. Simultaneously we observed the opposite process of oxidative stress...
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Critical limb ischemia and autologous cell therapy in diabetic foot disease, pathogenesis of Charcot osteoarthopathy.
Němcová, Andrea ; Jirkovská, Alexandra (advisor) ; Polák, Jan (referee) ; Prázný, Martin (referee)
Diabetic foot disease (DFD) is a serious complication of diabetes and, along with critical limb ischemia, significantly exacerbates the prognosis of patients. Peripheral arterial disease in patients with diabetes has an atypical clinical course, its diagnosis is challenging and is one of the most common causes of morbidity and mortality of patients with DFD. The aim of this dissertation focused on the diagnosis and treatment of DFD was to identify a suitable method for evaluating the effect of autologous cell therapy (ACT), to assess options for early diagnosis of Charcot osteoarthropathy (COA) and, possibly, to establish the association between the incidence of cardiovascular disease and DFD. In our studies concerning therapeutic vasculogenesis, we observed a significant increase in the antiangiogenic factor endostatin after ACT in contrast to its unchanged levels after standard percutaneous transluminal angioplasty; the transient increase in endostatin seems to be a marker of therapeutic vasculogenesis after ACT. A benefit of using calf muscle perfusion scintigraphy in the assessment of microcirculation and ACT effect was not clearly demonstrated. By contrast, a promising method for the evaluation of microcirculation and the effect of revascularization after ACT was MR spectroscopy of calf...
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The effect of regular physical activity on a long-term control of Type 1 Diabetes Mellitus
Schöppelová, Lucie ; Pelcl, Tomáš (advisor) ; Prázný, Martin (referee)
Introduction: Physical activity should be part of our everyday life. However, for people with Type 1 Diabetes Mellitus it is the most common cause of hypoglycemia. To control diabetes in the right way, it is therefore necessary to follow certain rules and recommendations that help preventing hypoglycemia while the physical activity remains beneficial at the same time. Aim of the work: The main aim of this study is to clarify the influence of physical activity in connection to long-term control of Type 1 Diabetes Mellitus. Methods: 102 respondents with diagnosed Type 1 Diabetes Mellitus in the age of 19-69 years participated in a quantitative analysis. This research was conducted in a form of multicentric examination at two independent medical centers. The data collection was done through questionnaires focused on physical activity and daily regime. The data from questionnaires were then compared to the values of glycated hemoglobin (HbA1C), HDL cholesterol and the total daily dose of insulin of certain patients. For statistical evaluation, analytical tools of Microsoft Office program were used (F-test and t-test). Results: We found correlation between HbA1C values in patients physically active for less than 2 hours/week compared to those who are physically active for more than 2 hours/week (62,72...
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Biomarkers in the diagnosis and treatment of diabetic complications
Šoupal, Jan ; Prázný, Martin (advisor) ; Rušavý, Zdeněk (referee) ; Rybka, Jaroslav (referee)
The main objective of this study was research on biomarkers used in both diagnosis and therapy of diabetic complications. The main focus of our work came to be on one of these biomarkers - glycemic variability (GV). High GV is linked with more frequent occurance of hypoglycemia. There are even indications it might contribute to development of diabetic complications. With modern technology - continuous glucose monitoring (CGM), we are now able to reliably describe, calculate and reduce GV. So far it is unclear whether increased GV can contribute to the development of microvascular complications (MVC) in type 1 diabetes (T1D). Studies published so far have assessed GV primarily from routine self-monitoring of blood glucose (SMBG) using glucometers. In the light of this uncertaity, the first part of this work compares GV calculated from CGM with the presence of MVC in T1D patients. GV calculated from CGM, but not from SMBG, proved to be significantly higher in T1D patients with MVC, even though there was no significant difference in glycated hemoglobin (HbA1c). This finding supports the hypothesis that higher GV is related to higher risk of MVC and that HbA1c does not describe diabetes control completely. Moreover, it was shown that GV calculated from SMBG is insufficient. There is still no fully...
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Nutritional Factors in Skeletal Muscle Insulin Resistance Development
Gojda, Jan ; Anděl, Michal (advisor) ; Saudek, František (referee) ; Prázný, Martin (referee)
Nutritional Factors in Skeletal Muscle Insulin Resistance Development Jan Gojda Abstract Background. Diet composition ranks among etiological factors of insulin resistance (IR) and diabetes. Vegans, people consuming exclusively plant-based diet, have significantly lower prevalence of IR and thus represent a suitable model population for study of nutritional factors on IR development. Branched chain amino acids (BCAA) ranks among these factors. Aims and hypothesis. Aim of the observational study was to prove that vegans have better glucoregulatory functions and thus to validate "vegan vs. omnivore" model. Aim of the consecutive interventional study was to prove in this model that dietary intervention with BCAA leads to a group sepcific changes in the insulin function mesures. Methods. 11 vegans and 10 omnivorous controls were recruited in the observational study. Hyperinsulinemic euglycemic clamp (HEC) and muscle (SM) biopsies (amount of intramyocellular lipids (IMCL), mtDNA and the activity of citrate synthase (CS)) were performed. 8 vegans and 8 omnivores were consequently subjected to the intervention with 15 or 20 g of BCAA respectively. The examination was performed at the baseline, after the intervention and after 6 months wash-out period: anthropometry, HEC, arginine test, SM biopsy (CS, activity of...
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Mikrocirculation in the diabetic foot syndrome
Tomešová, Jitka ; Lacigová, Silvie (advisor) ; Chlup, Rudolf (referee) ; Prázný, Martin (referee) ; Jirkovská, Alexandra (referee)
Abtrakt (EN) In spite of the fact that the diabetic foot syndrome is not considered a marginal complication of the patients with diabetes mellitus any more, its prevalence and incidence is not decreasing. The fact that early diagnosis and treatment or even prevention of foot ulcers is associated with a decrease in healthcare costs and, more importantly, with reducing patients' suffering, applies also in this case. The dissertation work originated in the Diabetologic Center of the Medical department I., University Hospital and Medical Faculty in Pilsen, Charles University in Prague, which has been dealing with diagnostic and therapeutic procedures in patients with diabetic foot syndrome for over 20 years. The examinations for diagnosis of the main etiologic factors, i.e. peripheral neuropathy and impaired perfusion, belong to already routine ordinary procedures here. My task was to move the diagnostics of this complication to earlier stages, even before the development of the ulcers, through diagnosing an impairment in skin microcirculation. The aim of the work was to evaluate reactivity of the skin microcirculation in patients with diabetes mellitus using laser doppler flowmetry and to introduce a new method - iontophoresis. Skin microcirculation assessment has become a center of interest of many studies...
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Microvascular reactivityand endothelial function in patients with diabetes mellitus and other endocrinopathies
Horová, Eva ; Prázný, Martin (advisor) ; Rybka, Jaroslav (referee) ; Rušavý, Zdeněk (referee)
(EN) Endothelial dysfunction is an early marker of atherosclerotic and cardiovascular complications. It is also a target of research aimed at the factors and mechanisms leading to the vascular impairment. The aim of the thesis was to evaluate the microvascular reactivity and endothelial function in patients with specific metabolic and hormonal disorders. Four separate studies are included in the thesis. First, the influence of hypercortisolism and associated diseases on microvascular reactivity was evaluated in patients with Cushing's syndrome. Second, the changes in microvascular reactivity and endothelial function after standard breakfast were studied in patients with type 2 diabetes. Next two studies were done in type 1 diabetic patients. The impact of acute hyperglycemia on microvascular reactivity was evaluated during hyperinsulinemic isoglycemic and hyperglycemic clamp. Finally, the influence of glycemic variability and insulin treatment on microvascular reactivity and its possible relationship were studied in type 1 diabetic patients. The results indicate that microvascular reactivity and endothelial function are, among other factors, influenced by insulinemia and insulin resistance. Microvascular reactivity was predominantly impaired by the arterial hypertension and diabetes in patients...
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Role of Helthy Life Style as Primary Prevention of Civilization Diseases
Pavlová, Veronika ; Zlatohlávek, Lukáš (advisor) ; Prázný, Martin (referee)
The main aim of this diploma thesis is to focus on prevention of chronic non-infectious diseases with epidemic occurrence (so called civilizational diseases). The theoretical part deals with each illness separately, it describes cause factors, which are or are not possible to influence, and introduces primary preventive precautions that are available in the Czech Republic nowadays. The author evaluates the qualities of these programmes and their potential to work as an effective primary prevention. Preventive effect of education was tested in the practical part of the thesis. Eating habits and physical activity of grammar school students from Strakonice were found out through the questionnaire method. Following lecture on healthy lifestyle involved the thinking of students and the second round of questioning was done one month later. Students' answers confirmed the possitive influence of the educational programme as the eating habits improved as well as frequency of their physical activity. Educational programmes play an important role in primary prevention of civilizational diseases. Key words: overweight, obesity, risk factors, primary preventive, eating habbits, physical activity, adolescence, education, nutrition, life style
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Insulin Resistance and Metabolic inFlexibility : the Influence of Renin Angiotensin System Inhibition
Wohl, Petr ; Pelikánová, Terezie (advisor) ; Prázný, Martin (referee) ; Vondra, Karel (referee)
Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...
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