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Mechanisms of insulin resistance in humans with focus on adipose tissue
Švehlíková, Eva ; Pelikánová, Terezie (advisor) ; Vondra, Karel (referee) ; Prázný, Martin (referee)
Endocrine activity of adipose tissue is implicated in the development of insulin resistance (IR). The thesis aimed to extend the knowledge of mechanisms contributing to IR. Study I - To investigate the effect of acute hyperinsulinaemia and acute angiotensin II type 1 receptor blockade (ARB) on plasma concentrations and subcutaneous adipose tissue (SAT) expressions of selected adipokines in patients with type 2 diabetes and healthy controls Study II - To investigate the effect of 3-week telmisartan treatment on insulin resistance and plasma concentrations and SAT expressions of selected adipokines in subjects with metabolic syndrome and impaired fasting glucose (IFG) Study III - To investigate the effect of prolonged hypertriglyceridaemia on plasma concentrations and SAT expressions of selected adipokines in patients with type 2 diabetes and healthy control subjects Study IV - To assess the plasma concentrations and SAT expressions of selected adipokines in subjects with different categories of glucose intolerance Methodology: Hyperinsulinaemic-euglycaemic clamp, Intralipid infusion and saline infusion were used to simulate specific metabolic conditions in vivo in 4 groups: 8 young healthy men, 11 overweight/obese patients with type 2 diabetes, 12 age-matched healthy controls and 12 overweight/obese patients...
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Optimalisation of insulin treatment - continuous subcutaneous insulin infusion
Jankovec, Zdeněk ; Rušavý, Zdeněk (advisor) ; Jirkovská, Alexandra (referee) ; Vondra, Karel (referee) ; Prázný, Martin (referee)
Introduction: To be able to prove the efficiency and benefit of the treatment including its safety on a wide range of patients (as opposed to more or less strictly selected groups form clinical studies), we started to gather data about patients in the Czech register of patients treated with continuous subcutaneous insulin infusion (CSII) - further referred to as Register. The obtained data not only represent an effective feedback on our clinical practice and treatment, but also they serve as an important argument for promotion of the CSII efficacy during the negotiations of reimbursement from the health insurance system (the CSII treatment is significantly more expensive compared to other MDI regimens). Aim of study: The aim of the first study were to present data on current situation and treatment results of CSII on wide unselected population of patients with diabetes mellitus in the Czech Republic. In the second study patients were evaluated to compare treatment indication, efficacy and safety with specific regard to the type of diabetes. Patient and methods: The national register of patients treated with CSII exists in the Czech Republic since 1998. We gather data from 52 departments of diabetology in the Czech Republic from patients with diabetes of all types treated with CSII. The data were...
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Other factors influencing daytime melatonin levels.
Rácz, Beáta ; Vondra, Karel (advisor) ; Kršek, Michal (referee) ; Sumová, Alena (referee)
Circadian rhythms are important for the adaptation of the organism to the changes of the environment. The internal biological clock (pacemaker) has a rhythm which is slightly longer or shorter than 24 hours. Melatonin is a pineal hormone produced during the dark period. The gastrointestinal tract is the main extrapineal source and the main source of melatonin during the light period. There are missing studies which are focused on the effects of the food on steroid hormones. Aim: To elucidate the effect of the food on selected hormone levels in two consequent studies of eight healthy nonsmoker premenopausal women in follicular phase of their menstrual cycle. Results: 1) 16 hours long monitoring: The levels of melatonin decreased significantly two hours after lunch. Cortisol levels were decreasing throughout the whole day and an additional decrease was found two hours after lunch. We were the first to report the significant connections of estradiol and SHBG to food intake. 2) Monitoring after different stimuli: Levels of melatonin increased 40 minutes after the i.v. application of glucose. In oGTT this increase was slower. Cortisol has decreased after the application of glucose, more apparently after its i.v. application. The breakfast led to increase of cortisol levels. OGTT and i.v.GTT caused some...
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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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Other factors influencing daytime melatonin levels.
Rácz, Beáta ; Vondra, Karel (advisor) ; Kršek, Michal (referee) ; Sumová, Alena (referee)
Circadian rhythms are important for the adaptation of the organism to the changes of the environment. The internal biological clock (pacemaker) has a rhythm which is slightly longer or shorter than 24 hours. Melatonin is a pineal hormone produced during the dark period. The gastrointestinal tract is the main extrapineal source and the main source of melatonin during the light period. There are missing studies which are focused on the effects of the food on steroid hormones. Aim: To elucidate the effect of the food on selected hormone levels in two consequent studies of eight healthy nonsmoker premenopausal women in follicular phase of their menstrual cycle. Results: 1) 16 hours long monitoring: The levels of melatonin decreased significantly two hours after lunch. Cortisol levels were decreasing throughout the whole day and an additional decrease was found two hours after lunch. We were the first to report the significant connections of estradiol and SHBG to food intake. 2) Monitoring after different stimuli: Levels of melatonin increased 40 minutes after the i.v. application of glucose. In oGTT this increase was slower. Cortisol has decreased after the application of glucose, more apparently after its i.v. application. The breakfast led to increase of cortisol levels. OGTT and i.v.GTT caused some...
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Mechanisms of insulin resistance and β - cell failure in type 2 diabetes. Effective diet against o minous octet
Kahleová, Hana ; Pelikánová, Terezie (advisor) ; Haluzík, Martin (referee) ; Vondra, Karel (referee)
Background and Aims: Dietary intervention is one of the key components in type 2 diabetes (T2D) management. Vegetarian diet is a promising alternative in the nutritional treatment of T2D. The aims of our study were: 1. To compare the effects of vegetarian and conventional diabetic diet with the same caloric restriction on insulin resistance, volume of visceral fat and plasma concentrations of oxidative stress markers after a 12-weeks-diet-intervention and subsequent 12-weeks of diet plus aerobic exercise training in subjects with T2D. 2. To explore the effect of 12 weeks of diet intervention and subsequent 12 weeks of diet combined with aerobic exercise training on -cell function and to evaluate the role of gastrointestinal peptides in subjects with T2D. 3. To study quality of life, Beck depression score and changes in eating behaviour in response to a vegetarian and a conventional diabetic diet. 4. To explore the role of changes in fatty acid composition of serum phospholipids in diet-induced changes in insulin sensitivity in subjects with T2D. 5. To follow-up our patients 1 year from the end of the intervention.
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The importance of determination of oxidative stress markers in exhaled breath condensate for the assessment of lung disease progression in patients with cystic fibrosis
Fila, Libor ; Kolář, Pavel (advisor) ; Macek, Milan (referee) ; Vondra, Karel (referee)
The aim of this study was to evaluate the relationship of oxidative stress (OS) marker s in exhaled breath condensate (EBC) in adult patients with cystic fibrosis (CF) to the severity of lung disease, nutritional status and systemic antioxidants and inflammatory markers, as well as to short - and medium - term development of pulmonary function and nutritional status, and finally to assess the response to treatment with inhaled corticosteroids (ICS). Methods: CF patients were examined in a stable phase of the disease during routine outpatient controls. EBC was collected using E C oScreen device (J aeger) in CF patients and in control group members. Nitrites and nitrates and 8 - isoprostane were examined using liquid chromatography and competitive enzyme immunoanalysis, respectively, in EBC as OS markers. Demographic data including the dominant pathogen of airway colonization and ICS treatment were recorded in CF patients. Lung function tests, chest X-ray s, nutritional statuses and systemic antioxidants and inflammatory markers were also examined using standard methods. The values of OS markers in EBC in patients with CF were compared with the control group and correlated to clinical parameters. Lung function tests and nutritional status es in CF patients were examined in one, three and five years intervals...
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Neuroactive steroids and addictions
Jandíková, Hana ; Vondra, Karel (advisor) ; Miovský, Michal (referee) ; Kršek, Michal (referee)
Neuroactive steroids are a group of steroid hormones which act non-genomically to influence the neuron excitability of neuronal synapses. Addictive substances can interfere with the synthesis of neuroactive steroids through many mechanisms, affecting their levels and changing their functionality. At the same time, neuroactive steroids play a role in the development of addiction, since their levels change during attempts to quit and therefore affect the success of treatments for addiction. This study focuses on the relationships between individual addictive substances and neuroactive steroids, the individual functional mechanisms and how they influence each other. It is generally known that addictive substances result in the release of anxiolytics that act on neuroactive steroids. This plays a role in the development of addiction. We also describe in detail the effect of smoking on steroid hormones and the endocrine system in general. Using tobacco addition as a model, we studied the relationship between addiction and neuroactive steroids. As part of my doctoral studies we performed a prospective study that followed changes in the steroid spectra induced by smoking as well as when quitting smoking. We also developed a predictive model to predict the likelihood of success in treating tobacco...
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The effect of transplantation therapy on diabetic complications
Bouček, Petr ; Pelikánová, Terezie (advisor) ; Vondra, Karel (referee) ; Rychlík, Ivan (referee)
Microangiopathic (retinopathy, nephropathy, and neuropathy) and macroangiopathic complications are the major causes of morbidity and mortality of diabetic patients. The main aims of the thesis were the assessment of the effect of pancreas transplantation with long-term normoglycemia on the course of small fibre diabetic neuropathy in type 1 diabetic patients and the comparison of the effect of kidney transplantation on the prognosis of type 2 diabetic and non-diabetic patients. Selected parameters of autonomic nerve function (cardiovascular reflex tests and spectral analysis of heart rate variability) and intraepidermal nerve fibre density in skin biopsies were assessed prospectively following simultaneous kidney and pancreas transplantation in type 1 diabetic patients. In type 2 diabetic patients, patient and graft survival and the occurrence of complications following kidney transplantation were retrospectively compared to matched non-diabetic controls. Advanced stages of diabetic neuropathy were present in type 1 diabetic patients at the time of transplantation and no significant improvement was seen in any of the assessed parameters following pancreas transplantation with long-term normoglycemia, which is indicative of the presence of irreversible structural small nerve fibre changes. Following kidney...
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