Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 146-172). Also available on the Internet.

Thesis (Ph. D.)--University of Wisconsin--Madison, 2000. / Includes bibliographical references (leaves 125-131).

Thesis (Ph. D.)--University of Wisconsin--Madison, 2000. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 125-131).

Aim/Objectives: There were two aims; improving type II diabetes glycaemic control; and enhancing the role of community pharmacists by engaging them in type II diabetes medicine management. Methods: This quantitative study collected data from both community pharmacists and patients. In a premises survey, 426 self-administered questionnaires were distributed to community pharmacies. In a knowledge survey, 125 questionnaires were distributed to community pharmacists. In a clinical trial, 40 community pharmacies were randomly assigned to be control (18) and intervention (22) premises. Each pharmacy recruited 4 or 5 patients with type II diabetes. 225 patients were recruited and assigned to receive usual pharmacist care (n=100) or a pre-defined pharmacist intervention (n=125). Results: Community pharmacists had good knowledge of diabetes with average scores 21/29 (±3.18). The differences between control and intervention groups in patients' HbA1c and FPG changes were not significant. In the intervention group patients' diabetes knowledge was significantly improved (p=0.031). In the intervention group HbA1c and FPG improved significantly and in the control group FPG improved significantly and HbA1c did not. Patients' self-reported self-management activities improved significantly around blood glucose measurements (p < 0.001) and physical exercising (p=0.001). Attitudes around the value of tight control of diabetes improved (p < 0.001). Conclusion: The findings suggest that community pharmacists in Libya may have the ability to improve type II diabetes care. The primary outcomes were not improved in intervention versus control. The before/after analysis showed significant improvement in primary outcomes in the intervention group and also in one of the primary outcomes in the control group. Patients' self-reported self-care activities and attitudes improved significantly in the intervention group.

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...

Metabolic pathways in adipose tissue affect the whole-body energy homeostasis. De novo lipogenesis and futile metabolic cycling based on lipolysis and fatty acid re-esterification which is engaged in regulation of fatty acid level in bloodstream are occuring there. These processes are partly regulated by nuclear receptor PPARγ. Mitochondrial biogenesis and oxidative phosphorylation in adipocytes are controlled by interacting of PPARγ with transcriptional coactivators PGC-1α and PGC-1β. The aims of this thesis were to find out whether PGC-1β is connected with regulation of futile cycling and de novo lipogenesis in white adipose tissue and also how specific inactivation of PGC-1β gene in adipose tissue affects phenotype of mice during short-term cold exposure or treatment based on high fat diet enriched by n-3 polyunsaturated fatty acids in combination with mild calorie restriction. The results show that inactivation of PGC-1β probably does not affect futile cycling based on lipolysis and fatty acid re-esterification. In mice with PGC-1β ablation compensation in weight of brown adipose tissue was observed as well as increase in the gene expresion of nuclear receptors PPAR, transcriptional coactivator PGC-1α and UCP1 during cold exposure. Even though the inactivation of PGC-1β in brown adipose tissue...

Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder linked with the development of specific complications and comorbidities that negatively affect life quality and greatly increase the risk of an early death. The main goal of T2D treatment, which in common clinical practice comprises lifestyle changes and pharmacotherapy, is to delay onset of these complications. Evidence from many recent studies shows the ability of some interventional methods to induce remission of T2D, meaning a major improvement or complete disappearance of T2D symptoms. Besides bariatric surgery procedures, some dietary regimens such as low-energy diet, low-carbohydrate diet and intermittent fasting, can also lead to T2D remission. Attributes of these dietary regimens, especially their effect in T2D treatment, is summarized in the theoretical part of this theses. The aim of the practical part of this thesis was to assess the effect of the dietary regimens mentioned above on morphometric and biochemical parameters associated with T2D by clinical and survey research. In most of the subjects with T2D, the individual dietary regimens, more precisely low-energy diet and low-carbohydrate diet, decreased body weight, where the weight loss induced by low-carbohydrate diet was caused by major decrease in the amount...

Zusammenfassung Thure Adler Der Streptozotozin-induzierte Diabetes in der transgenen CD4/DR17-Maus Aus dem Institut für Immunologie der Veterinärmedizinischen Fakultät und dem Institut für Klinische Immunologie und Transfusionsmedizin der Medizinischen Fakultät der Universität Leipzig, 80 Seiten, 24 Abbildungen, 20 Tabellen, 217 Literaturangaben Die Verwendung transgener Tiere, die humane Moleküle exprimieren, gewinnt zunehmend an Bedeutung bei der Erforschung der Funktionen solcher Moleküle in Krankheitsprozessen und bei der experimentellen Erprobung neuartiger Therapieverfahren, in denen solche Moleküle die Zielstrukturen darstellen. In der vorliegenden Arbeit wurde die CD4/DR17-Maus, welche das humane CD4- und das DR17-Molekül exprimiert, im MLD-STZ-induzierten Diabetes, einem Tiermodell für den Typ 1 Diabetes, eingesetzt. Die funktionelle Beteiligung der Transgene wurde durch einen Vergleich mit Segreganten untersucht, denen die Transgene teilweise fehlen. Als klinische Parameter sind Blutglukose und Glukosetoleranz erfaßt worden, histopathologisch wurden Insulitis und Insulingehalt der Inselzellen bestimmt. Ferner wurde getestet, ob sich durch Verabreichung von monoklonalen Antikörpern, die gegen das transgene hCD4- oder gegen das CD8-Molekül gerichtet sind, dieser STZ-induzierte Diabetes beeinflussen läßt. Mit Hilfe der durchflußzytometrischen Immunfluoreszenzanalyse von Blutzellen wurde zusätzlich überprüft, ob Veränderungen auf T-Zellen hinsichtlich der Expression der Aktivierungsmarker CD25, CD69 und CD71 während des STZ-induzierten Diabetes auftreten. Es wurde gezeigt, dass die CD4/DR17-transgene Maus nach der Behandlung mit mehrfachen subdiabetogenen Dosen von Streptozotozin eine transiente Hyperglykämie entwickelt, die mit einer verringerten Glukosetoleranz sowie Insulitiden und einem Rückgang des Insulingehaltes in den Langerhans’schen Inseln einhergeht. Vergleiche mit Segreganten zeigen, dass die Expression beider transgener Merkmale zur maximalen Ausprägung einer schwergradigen Insulitis beiträgt. Die Anwendung von monoklonalen Antikörpern gegen das transgene hCD4-Molekül nach Beginn der STZ-Behandlung hat den Diabetes nicht wirkungsvoll verzögert. Dagegen milderte eine Behandlung mit Antikörpern, die gegen das CD8-Molekül gerichtet sind, den Diabetesverlauf. Während des STZ-Diabetes veränderte sich die Expression von Aktivierungsmarkern auf Lymphozyten des peripheren Blutes nicht signifikant. Die Arbeit belegt, dass die CD4/DR17-Maus suszeptibel gegenüber der Induktion eines experimentellen Diabetes mit mehrfachen subdiabetogenen Dosen von Streptozotozin ist. Die transgenen Moleküle hCD4 und DR17 sind dabei am Krankheitsprozeß beteiligt. / Summary Thure Adler The streptozotocin-induced diabetes in the transgenic CD4/DR17 mouse From the Institute of Immunology, Faculty of Veterinary Medicine and the Institute of Clinical Immunology and Transfusion Medicine, Faculty of Medicine, University of Leipzig 80 pages, 24 figures, 20 tables, 217 references Today, transgenic animals that express human molecules are getting important tools in functional studies and experimental, therapeutical attempts, that target these molecules. In this study, the CD4/DR17 mouse expressing the human CD4 and the human DR17 molecules and with a defective murine CD4 gene, was used in the multiple low-dose streptozotocin-induced (MLD-STZ) diabetes model, a model for type 1 diabetes. The functional involvement of the transgenic molecules in the development of the MLD-STZ-diabetes was analysed by comparing CD4/DR17 mice and segregants that lack one or more of the transgenes. The described parameters included the measurement of blood glucose levels and oral glucose tolerance tests, histopathologically grading of insulitis and determination of the content of insulin in pancreatic islets by immunohistological methods. In addition, the model was used to test the potential therapeutic effect of the administration of monoclonal antibodies against hCD4 or CD8. Furthermore, alterations of the expression of the activation markers CD25, CD69 and CD71 during the experimentally induced diabetes has been measured by FACS analysis. The study shows, that CD4/DR17 mice develop a transient hyperglycemia after MLD-STZ treatment, accompanied by a reduced tolerance to oral glucose, insulitis and the reduction of the content of insulin in the pancreatic islets. The full incidence of insulitis requires the expression of both transgenes. The treatment performed with monoclonal antibodies against the transgenic hCD4 after STZ-treatment could not meliorate the diabetic course, while the treatment with anti CD8 antibodies moderated the diabetic process. After STZ-treatment the expression of activation marker of peripheral T-cells did not alter significantly. Thus, the CD4/DR17 mouse is shown to be susceptible to the induction of experimental diabetes with MLD-STZ. The transgenic molecules CD4 and DR17 are involved in the pathogenesis of the disease.

The topic of the diploma thesis is the influence of a low-carbohydrate diet on the treatment of type 1 diabetes mellitus. It is an autoimmune disease for which it is necessary for patients to administer insulin. The selection of suitable sports activities, good health and mental condition and, above all, the adjustment of eating habits also contribute to the successful compensation of diabetes. This work demonstrates a low-carbohydrate diet as one of the possibilities diabetics can eat. The work is divided into two parts, theoretical and practical. The theoretical part briefly describes the disease and presents the recommended and a low- carbohydrate diet. The following section also addresses physical activity. It describes the issues of sports for people with diabetes who are on a regular diet, as well as on low-carbohydrate diet. The practical part shows the results of glucose sensors (Free Style Libre, Dexcom G6 and Medtronic), which continuously measure blood sugar levels. In the practical part, eight respondents with type 1 diabetes, who switched the recommended diet for a low-carbohydrate diet, were surveyed in the form of a questionnaire. The purpose of the questionnaire was to assess the effects of switching to a low- carbohydrate diet on: the compensation of diabetes; the frequency of...