O Diabetes Mellitus do tipo 1 (DM1) é uma doença metabólica multifatorial caracterizada por hiperglicemia e hipoinsulinemia crônicas, decorrentes da destruição progressiva das células &#946 pelo sistema imunológico. Durante a progressão do DM1, as ilhotas de Langherhans são invadidas por células do sistema imune que secretam citocinas pró-inflamatórias, gerando um quadro denominado insulite. A exposição das células &#946 a essas citocinas leva a ativação de diversas vias de sinalização que aumentam o estresse oxidativo e de retículo endoplasmático, contribuindo para a indução da morte das células &#946. Existem muitos estudos que investigam as vias moleculares que levam à destruição da célula durante o DM1, contudo é necessário um melhor entendimento da regulação e contribuição dessas diferentes vias para o desenvolvimento dessa patologia para que se possa desenhar terapias mais apropriadas para impedir seu desenvolvimento ou até mesmo para se atingir uma cura. Algumas das dificuldades encontradas na aplicação desses estudos estão relacionadas ao fato de que eles são conduzidos em sua maioria em células &#946 ou ilhotas isoladas em cultura. Sabe-se que há uma importante regulação entre os diferentes tipos celulares presentes na ilhota e também entre as células da ilhota e as células adjacentes a ela, o que, sem dúvida, influencia no destino da célula &#946 frente a um ataque autoimune. Este trabalho visou aperfeiçoar o conhecimento acerca do comportamento das células da ilhota pancreática frente ao desenvolvimento do DM1, utilizando técnicas de imunomarcação em cortes histológicos pancreáticos de três modelos animais de DM1. No primeiro modelo: Influência do exercício físico na indução do DM1, mostramos que o exercício físico é capaz de prevenir a destruição das células &#946 e potencialmente estar envolvido na transdiferenciação celular para recuperação de células endócrinas na ilhota desses animais. No segundo modelo: Efeito de NOX1 e NOX2 na viabilidade e função de células &#946 \", observamos que a presença dessas NADPH oxidases parece ter influência na estrutura e provavelmente na viabilidade de células &#946. No terceiro modelo: Papel de HNF4 &#945 na viabilidade e função das células &#946, mostramos que a imunomarcação das ilhotas de animais KO para esse fator de transcrição nas células &#946 é uma ferramenta de extrema importância para esse estudo. O desenvolvimento desse trabalho possibilita que a investigação de diferentes vias envolvidas na destruição das células &#946 seja realizada no ambiente em que essas células se encontram, permitindo avaliar a ativação de vias especificas, como por exemplo ativação de NF-kB e validar os resultados observados em células isoladas. / Type 1 Diabetes Mellitus (DM1) is a multifactorial metabolic disease characterized by chronic hyperglycemia and hypoinsulinemia, which is due to the progressive and specific destruction of &#946 cells by the immune system. During the progression of DM1, the islets of Langherhans are invaded by cells of the immune system that secrete proinflammatory cytokines, in a process called insulitis. Exposure of &#946 cells to these cytokines leads to the activation of several signaling pathways that increase oxidative and endoplasmic reticulum stress, contributing to the -cell death. There are many studies that investigate the molecular pathways that lead to the destruction of the &#946-cell during DM1, but a better understanding of the regulation and contribution of these different pathways to the development of this pathology is necessary in order to design more appropriate therapies to prevent their development or even to achieve a cure. Some of the difficulties encountered in the application of these studies are related to the fact that they are conducted mostly on &#946-cells or isolated islets in cell culture. It is known that there is an important regulation between the different cell types present in the islet and also between the islet cells and the cells adjacent to it, which undoubtedly influences the fate of the &#946-cell against an autoimmune attack. This work aimed to improve the knowledge about the behavior of pancreatic islet cells in the development of DM1, using immunostaining techniques in pancreatic histological sections of three animal models of DM1. In the first model, \"Influence of physical exercise on the induction of DM1\", we showed that physical exercise is able to prevent the destruction of &#946 cells and potentially be involved in cell transdifferentiation for the recovery of endocrine cells in the islet of these animals. In the second model, \"Effect of NOX1 and NOX2 on viability and &#946 cell function\", we observed that the presence of these NADPH oxidases appears to influence the structure and probably the viability of &#946 cells. \"In the third model:\" Role of HNF4&#945 in viability and &#946 cell function, we show that the immunostaining of islets of KO animals for this transcription factor in &#946 cells is a tool of paramount importance for this study. The development of this work enables the investigation to be performed in the environment of these cells, allowing to evaluate the activation of specific pathways and validate the results observed in isolated cells.

Exercise has a wide range of benefits for patients with type 1 diabetes, including improvements in body composition, cardiovascular risk profile and glycaemic control. Unfortunately, exercise also increases the risk of hypoglycaemia in children with type 1 diabetes, both at the time of exercise and for many hours afterwards. The availability of clear, evidence-based guidelines regarding appropriate adjustments in carbohydrate intake or insulin doses may help to prevent this exercise associated hypoglycaemia. However, current guidelines regarding exercise in children with type 1 diabetes rely heavily on adult literature or the consensus of experts. Therefore, further studies are needed in young people with diabetes to document the metabolic responses during and following exercise. In particular, the mechanisms underlying hypoglycaemia occurring many hours after exercise require further exploration. In addition, as children often exercise in the afternoon, studies performed at this time of the day are more likely to be transferrable to a real life situation. For this reason, we studied adolescents with type 1 diabetes to investigate physiological responses to exercise, focusing on afternoon activity and employing a novel variation of the euglycaemic insulin clamp technique. The core experiments involved studying diabetic adolescents on two occasions in a counterbalanced, paired design during and after afternoon exercise. Insulin was infused at a constant rate based on the subjects' usual daily insulin dose and glucose was infused to maintain euglycaemia. At 1600 hrs subjects either exercised at a moderate intensity (95% of their lactate threshold) for 45 minutes on a cycle ergometer (exercise study), or sat on the ergometer without exercising (rest study). Using this experimental design, it was found that glucose infusion rates (GIR) to maintain euglycaemia were elevated during and shortly following exercise and again from 7-11 hours after exercise compared with the rest study. Counterregulatory hormone levels were similar between the exercise and rest studies except for peaks in noradrenaline, cortisol and growth hormone levels at the end of exercise. Glucagon and adrenaline levels did not increase with exercise. The observed biphasic increase in glucose requirements paralleled the observed clinical risk of hypoglycaemia immediately during exercise and the delayed risk of hypoglycaemia which often occurs overnight.

<p>Variation of diabetes incidence over time in countries with different incidence levels and socio-economic conditions, and in an age span beyond the childhood years, may give clues for diabetes causes.</p><p><i>Materials:</i> Data from prospective type 1 diabetes registers in Sweden and Lithuania in children (0-14 years) and young adults (15-34 and 15-39 years, respectively). Number of infections recorded in health care booklets (117 cases; 270 controls); interview about the dietary intake one-year before the diagnosis and routinely recorded growth data (99 cases; 180 controls). </p><p><i>Results:</i> The incidence of type 1 diabetes in Sweden and Lithuania differed most in the younger age groups, 28.9 and 7.5/100,000/year in 0-14-year group, respectively. During 1983-2000 incidence increased in 0-14-year old children in both countries, but the pattern of change differed. During 1983-1998 the incidence increased in Swedish children, but tended to decrease in young adults, with no increase in the age group below 35 years, indicating that the increase of childhood diabetes may be due to a shift towards a younger age at diagnosis. Within a low-incidence country Lithuania there was an urban-rural gradient of incidence, especially in the younger age groups, that seemed to follow poverty distribution: incidence in the 0-39-year group was 7.1, 9.0 and 8.8/100,000/year in rural areas, towns and cities, respectively, p<0.001.</p><p>Exposure to one or more non-specific infection during the first half-year of life reduced diabetes risk: odds ratios (95%-CI) in 0-14 and 5-14-year groups were (0.60; 0.37-0.98) and (0.47; 0.26-0.87), respectively. Higher energy intake and weight-for-age were independent diabetes risk factors: odds ratios for medium and high levels of energy were 1.33 (0.52-3.42) and 5.23 (1.67-16.38), and for weight-for-age 3.20 (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates, disaccharides and sucrose in particular, increased diabetes risk independently of the high intake of energy.</p><p><i>Conclusion:</i> Environmental factors associated with socio-economic conditions in childhood may be important for the occurrence of type 1 diabetes. Lack of exposure to microbial antigens early in life, higher intake of energy and more rapid growth may contribute to the increase of childhood-onset diabetes observed in many countries.</p>

Variation of diabetes incidence over time in countries with different incidence levels and socio-economic conditions, and in an age span beyond the childhood years, may give clues for diabetes causes. Materials: Data from prospective type 1 diabetes registers in Sweden and Lithuania in children (0-14 years) and young adults (15-34 and 15-39 years, respectively). Number of infections recorded in health care booklets (117 cases; 270 controls); interview about the dietary intake one-year before the diagnosis and routinely recorded growth data (99 cases; 180 controls). Results: The incidence of type 1 diabetes in Sweden and Lithuania differed most in the younger age groups, 28.9 and 7.5/100,000/year in 0-14-year group, respectively. During 1983-2000 incidence increased in 0-14-year old children in both countries, but the pattern of change differed. During 1983-1998 the incidence increased in Swedish children, but tended to decrease in young adults, with no increase in the age group below 35 years, indicating that the increase of childhood diabetes may be due to a shift towards a younger age at diagnosis. Within a low-incidence country Lithuania there was an urban-rural gradient of incidence, especially in the younger age groups, that seemed to follow poverty distribution: incidence in the 0-39-year group was 7.1, 9.0 and 8.8/100,000/year in rural areas, towns and cities, respectively, p&lt;0.001. Exposure to one or more non-specific infection during the first half-year of life reduced diabetes risk: odds ratios (95%-CI) in 0-14 and 5-14-year groups were (0.60; 0.37-0.98) and (0.47; 0.26-0.87), respectively. Higher energy intake and weight-for-age were independent diabetes risk factors: odds ratios for medium and high levels of energy were 1.33 (0.52-3.42) and 5.23 (1.67-16.38), and for weight-for-age 3.20 (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates, disaccharides and sucrose in particular, increased diabetes risk independently of the high intake of energy. Conclusion: Environmental factors associated with socio-economic conditions in childhood may be important for the occurrence of type 1 diabetes. Lack of exposure to microbial antigens early in life, higher intake of energy and more rapid growth may contribute to the increase of childhood-onset diabetes observed in many countries.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2010. / Härtill 4 uppsatser.

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

School plays critical roles in facilitating and inhibiting the safety, development, and well-being of adolescents with T1DM. However, their school-based lived experiences have been under-investigated. This study aimed to explore those experiences for adolescents with T1DM in Taiwan. In conducting the study, Heidegger’s hermeneutic phenomenological approach was used. Fourteen Taiwanese adolescents with T1DM were enrolled between June 2009 and July 2010 through purposive snowball sampling. Data were collected using audio-recorded, semi-structured interviews and analyzed using the hermeneutic circle and West’s (1998) structural analysis steps, supported by qualitative analysis software NVivo 9.0. Reflective journaling, peer debriefing, memo writing, and member checking were performed to enhance the trustworthiness of the findings. Six interrelated themes were identified in the adolescents’ school-based lived experiences. They are (a) the same and different, (b) covert and overt, (c) hyper- and hypoglycemia, (d) independent and dependent, (e) derailing and being on track, and (f) dark clouds and silver lining. In the stressful context of school, the adolescents’ diabetes self-management is challenged. Multiple factors, including unaccepted disease identity; social anxiety and pressure; intrusive, ignorant school personnel and classmates; and transition to independent self-management threaten the adolescents’ health and well-being at school. To optimize diabetes self-management effectiveness, interventions should include the adolescents and their parents, classmates, and school personnel to ease burdens that the adolescents bear. Future interventions should also facilitate the adolescents’ autonomy, self-efficacy, diabetes knowledge and self-management, and capacity to alleviate social pressure. / text

Tyrimo tikslas – ištirti sąsajas tarp paauglių, sergančių cukriniu diabetu, psichosocialinio prisitaikymo ir tėvų pastangų kontroliuoti savo vaikų ligą. Tyrime dalyvavo 11–16 metų paaugliai, kurie serga cukriniu diabetu ilgiau nei vienerius metus, ir jų tėvai (vienas iš tėvų). Iš viso buvo apklausti 73 paaugliai (36 vaikinai ir 37 merginos) ir 73 jų tėvai (21 vyras ir 52 moterys). Paauglių psichosocialinis prisitaikymas buvo matuojamas R. Goodman Galių ir Sunkumų klausimynu, kurį sudaro 25 teiginiai apie teigiamas ir neigiamas savybes, iš kurių susideda 6 klausimyno skalės: socialumas, hiperaktyvumas, emociniai simptomai, elgesio problemos, problemos su bendraamžiais ir bendra sunkumų skalė. Tėvų ligos kontrolė buvo matuojama L. Gonder-Frederick Hipoglikemijos baimės klausimynu (tėvų versija), kurį sudaro 26 teiginiai apie tėvų, kurių vaikai serga cukriniu diabetu, elgesį, kad išvengtų hipoglikemijos ir nerimavimus, kad jų vaiką gali ištikti hipoglikemija; ir vertinama glikemijos kontrolė, kurią parodo glikuoto hemoglobino koncentracija kraujyje. Tyrimo rezultatai parodė, kad vaikinų ir merginų psichosocialinis prisitaikymas skiriasi. Vaikinų grupėje labiau išreikštas socialumas susijęs su didesnes tėvų hipoglikemijos baime, o labiau išreikštos elgesio problemos susijusios su mažesne tėvų hipoglikemijos baime. Merginų grupėje psichosocialinis prisitaikymas su tėvų hipoglikemijos baime nesusijęs. Vaikinų ir merginų geresnė glikemijos kontrolė susijusi su didesne tėvų... [toliau žr. visą tekstą] / The aim of the study was to assess the relationships between psychosocial functioning in youth with type 1 diabetes mellitus, parental fear of hypoglycemia and glycemic control. The subject of the study was 11-16 years-old youths with type 1 diabetes mellitus diagnosed more than 1 year ago and one of their parents. Overall there were 73 youth (36 boys and 37 girls) and 73 their parents (21 men and 52 women). Psychosocial functioning was assessed with Strengths and Difficulties Questionnaire of R. Goodman. It has 25 items about good and bad habits which turn into 6 scales: prosocial, hyperactivity, emotional symptoms, conduct problems, peer problems and total difficulties. Parental fear of hypoglycemia was assessed with Hypoglycemia Fear Survey (patent version) of L. Gonder-Frederick. It has 26 items about parent’s behavior in order to avoid hypoglycemia and worries of child having a low. Glycemic control was evaluated by glycated hemoglobin concentration. The results of the study showed that psychosocial functioning is different in boys and girls. Higher prosocial in boys was related to higher parental fear of hypoglycemia, higher conduct problems was related to lower parental fear of hypoglycemia. No relations were found in girls psychosocial functioning and parental fear of hypoglycemia. Greater glycemic control was related to higher parental fear of hypoglycemia in both boys and girls. Higher hiperaktivity, emotional symptoms, conduct problems and total difficulties in... [to full text]

In der Literatur wird von einem kontinuierlichen, weltweiten Anstieg der Inzidenz des Typ 1 Diabetes mellitus unter Kindern und jungen Erwachsenen, insbesondere in der Altersgruppe der unter 20-Jährigen, berichtet. Die multizentrische Studie EURODIAB untersuchte in den Jahren 1989-2003 die Inzidenz des Typ 1 Diabetes in 17 europäischen Ländern und bestätigte mit deren Ergebnissen diese weltweite Tendenz. Die Akzelerator Hypothese von Wilkin aus dem Jahr 2001 sieht die Ursache hierfür durch einen übermäßigen Gewichtsanstieg bedingt, da auch die Inzidenz übergewichtiger Kinder innerhalb der letzten Jahre zugenommen hat. Demnach sei die Anzahl Betroffener insgesamt gleich, jedoch in jungen Jahren (bis 15 Jahre) erhöht. Folglich sei Übergewicht mit Insulinresistenz ein Triggerfaktor für eine raschere Progression der Erkrankung und würde zu einem vorzeitigen klinischen Ausbruch des Typ-1-Diabetes beitragen. Im Rahmen dieser Dissertation verglichen wir anthropometrische Geburtsdaten von 1.117 Kindern mit Typ 1 Diabetes mellitus, deren Erstmanifestation zwischen 1988 und April 2013 lag, mit einer Kontrollgruppe, die bezüglich Geschlecht, Alter und Schwangerschaftswoche angepasst wurde (n=54.344). Des Weiteren wurden die Kinder mit Diabetes entsprechend ihres Alters bei Manifestation bestimmten Gruppen zugeordnet: G1:0-4,9 Jahre; G2:5 9,9 Jahre; G3:10-20 Jahre. Diese Unterteilung wurde vorgenommen, um festzustellen, ob Kinder, bei denen eine Diabetes Erkrankung früher klinisch manifest wird, zur Geburt bzw. zum Zeitpunkt der Diagnosestellung einen höheren Gewichts SDS aufweisen als Kinder, welche erst in späteren Jahren betroffen sind. Zusätzlich wurden Verlaufsdaten des BMI SDS von 540 Studienkindern vor, zu und nach Manifestation ermittelt und mit einer gesunden Kontrollpopulation (n=134.249) verglichen. Hierbei zeigten Kinder und Jugendliche mit Typ 1 Diabetes im Vergleich zu Stoffwechselgesunden signifikant erhöhte Geburtsgewicht SDS Werte. Es konnte jedoch keine signifikante Abhängigkeit zwischen einer vorzeitigen Diabetes-Manifestation und einem erhöhten Geburtsgewichts bzw. einem erhöhten BMI SDS zum Zeitpunkt der Manifestation gezeigt werden. Ebenso blieb der laut Wilkin zu erwartende Gewichtsanstieg 4 Jahre vor Ausbruch der Erkrankung aus. Kinder mit Diabetes verlieren, wie erwartet, zur Manifestation an Gewicht und erreichen nach ungefähr einem Jahr ihr Ausgangsgewicht. In den Folgejahren sind Kinder mit Typ 1 Diabetes signifikant schwerer als die Kontrollgruppe. Aufgrund dieser Ergebnisse müssen wir die von Wilkin postulierte „Akzelerator Hypothese“ widerlegen.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 2 uppsatser.