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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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Pathobiochemistry of diabetes mellitus and its complications - oxidative stress, microinflammation and genetic predisposition.
Škrha, Jan ; Kalousová, Marta (advisor) ; Rybka, Jaroslav (referee) ; Bendlová, Běla (referee)
Diabetes is a chronic disease with high prevalence and significant morbidity. Chronic changes in the wall of small and large vessels lead to main diabetes complications. Apart from long- term hyperglycemia, several factors are involved in the development of diabetes vasculopathy. The aim of this work was to describe new early biomarkers of these vascular changes, to identify risky patients. Alongside, gene polymorphisms involved in protective pathways of glucose metabolism were studied. In three human studies with Type 1 (T1D) and Type 2 (T2D) diabetes patients special biochemical parameters of receptor for advanced glycation endproducts (RAGE) and its ligands, deglycation enzyme glyoxalase 1 (GLO1) and fructosamine 3-kinase (FN3K) gene polymorphisms were analyzed. Non-invasive measurement of glycation by skin autofluorescence (SAF) was assessed in all subjects. Soluble RAGE, HMGB1 and endothelial dysfunction markers were increased in patients with diabetes as compared with controls, however the differences between T1D and T2D were not significant. For the first time, an association between FN3K (rs1056534) and (rs3848403) polymorphism and sRAGE concentration in diabetes was shown. GLO1 (rs4746) polymorphism was associated with changes in endothelial dysfunction. Patients with diabetes had higher...
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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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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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Hypoglycaemia as Acute Complication of Diabetes Mellitus
Krnáčová, Veronika ; Macek, Karel (advisor) ; Rybka, Jaroslav (referee) ; Švihovec, Jan (referee)
Title of thesis: Hypoglycaemia as acute complication of diabetes mellitus Author of thesis: Mgr. Veronika Krnáčová (roz. Vlčková) This thesis was focused on hypoglycaemia as adverse drug reaction of rosiglitazone, pioglitazone, nateglinide and repaglinide, which have been launched to the UK market and on severe hypoglycaemia (SH) requiring the assistance of Emergency medical service (EMS) in region of Hradec Králové. Observed factors were described in two separate sections. Hypoglycaemia as adverse drug reaction of selected oral antidiabetics Aim The aim of this study was to quantify the incidence of hypoglycaemic events during the first nine months of treatment with newly launched oral antidiabetics, rosiglitazone, pioglitazone, nateglinide or repaglinide, prescribed by general practitioners in England, to observe pattern of these events over time, to look for patients' characteristics which could influence the incidence of hypoglycaemia and to analyse the relationship between use of concomitant anti-diabetic therapies and the incidence of hypoglycaemia in patients treated with pioglitazone. Methods We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, cohort study. Incidence...
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Gene polymorphisms of antioxidant enzymes and diabetes mellitus
Flekač, Milan ; Škrha, Jan (advisor) ; Bendlová, Běla (referee) ; Rybka, Jaroslav (referee)
Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL(high-density lipoproteins), preserves LDL (low density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity.This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0,05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0,01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110±68 nmol/ml/min) and T2DM patients (118±69 nmol/ml/min) compared to the control persons (203±58 nmol/ml/min), both p<0,01. The presence of MM and QQ...
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