京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19996号 / 工博第4240号 / 新制||工||1656(附属図書館) / 33092 / 京都大学大学院工学研究科電気工学専攻 / (主査)教授 土居 伸二, 教授 小林 哲生, 准教授 蛯原 義雄 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

[EN] Type 1 diabetes mellitus is a chronic and incurable disease that affects millions of people all around the world. Its main characteristic is the destruction (totally or partially) of the beta cells of the pancreas. These cells are in charge of producing insulin, main hormone implied in the control of blood glucose. Keeping high levels of blood glucose for a long time has negative health effects, causing different kinds of complications. For that reason patients with type 1 diabetes mellitus need to receive insulin in an exogenous way. Since 1921 when insulin was first isolated to be used in humans and first glucose monitoring techniques were developed, many advances have been done in clinical treatment with insulin. Currently 2 main research lines focused on improving the quality of life of diabetic patients are opened. The first one is concentrated on the research of stem cells to replace damaged beta cells and the second one has a more technological orientation. This second line focuses on the development of new insulin analogs to allow emulating with higher fidelity the endogenous pancreas secretion, the development of new noninvasive continuous glucose monitoring systems and insulin pumps capable of administering different insulin profiles and the use of decision-support tools and telemedicine. The most important challenge the scientific community has to overcome is the development of an artificial pancreas, that is, to develop algorithms that allow an automatic control of blood glucose. The main difficulty avoiding a tight glucose control is the high variability found in glucose metabolism. This fact is especially important during meal compensation. This variability, together with the delay in subcutaneous insulin absorption and action causes controller overcorrection that leads to late hypoglycemia (the most important acute complication of insulin treatment). The proposals of this work pay special attention to overcome these difficulties. In that way interval models are used to represent the patient physiology and to be able to take into account parametric uncertainty. This type of strategy has been used in both the open loop proposal for insulin dosage and the closed loop algorithm. Moreover the idea behind the design of this last proposal is to avoid controller overcorrection to minimize hypoglycemia while adding robustness against glucose sensor failures and over/under- estimation of meal carbohydrates. The algorithms proposed have been validated both in simulation and in clinical trials. / [ES] La diabetes mellitus tipo 1 es una enfermedad crónica e incurable que afecta a millones de personas en todo el mundo. Se caracteriza por una destrucción total o parcial de las células beta del páncreas. Estas células son las encargadas de producir la insulina, hormona principal en el control de glucosa en sangre. Valores altos de glucosa en la sangre mantenidos en el tiempo afectan negativamente a la salud, provocando complicaciones de diversa índole. Es por eso que los pacientes con diabetes mellitus tipo 1 necesitan recibir insulina de forma exógena. Desde que se consiguiera en 1921 aislar la insulina para poder utilizarla en clínica humana, y se empezaran a desarrollar las primeras técnicas de monitorización de glucemia, se han producido grandes avances en el tratamiento con insulina. Actualmente, las líneas de investigación que se están siguiendo en relación a la mejora de la calidad de vida de los pacientes diabéticos, tienen fundamentalmente 2 vertientes: una primera que se centra en la investigación en células madre para la reposición de las células beta y una segunda vertiente de carácter más tecnológico. Dentro de esta segunda vertiente, están abiertas varias líneas de investigación, entre las que se encuentran el desarrollo de nuevos análogos de insulina que permitan emular más fielmente la secreción endógena del páncreas, el desarrollo de monitores continuos de glucosa no invasivos, bombas de insulina capaces de administrar distintos perfiles de insulina y la inclusión de sistemas de ayuda a la decisión y telemedicina. El mayor reto al que se enfrentan los investigadores es el de conseguir desarrollar un páncreas artificial, es decir, desarrollar algoritmos que permitan disponer de un control automático de la glucosa. La principal barrera que se encuentra para conseguir un control riguroso de la glucosa es la alta variabilidad que presenta su metabolismo. Esto es especialmente significativo durante la compensación de las comidas. Esta variabilidad junto con el retraso en la absorción y actuación de la insulina administrada de forma subcutánea favorece la aparición de hipoglucemias tardías (complicación aguda más importante del tratamiento con insulina) a consecuencia de la sobreactuación del controlador. Las propuestas presentadas en este trabajo hacen especial hincapié en sobrellevar estas dificultades. Así, se utilizan modelos intervalares para representar la fisiología del paciente, y poder tener en cuenta la incertidumbre en sus parámetros. Este tipo de estrategia se ha utilizado tanto en la propuesta de dosificación automática en lazo abierto como en el algoritmo en lazo cerrado. Además la principal idea de diseño de esta última propuesta es evitar la sobreactuación del controlador evitando hipoglucemias y añadiendo robustez ante fallos en el sensor de glucosa y en la estimación de las comidas. Los algoritmos propuestos han sido validados en simulación y en clínica. / [CA] La diabetis mellitus tipus 1 és una malaltia crònica i incurable que afecta milions de persones en tot el món. Es caracteritza per una destrucció total o parcial de les cèl.lules beta del pàncrees. Aquestes cèl.lules són les encarregades de produir la insulina, hormona principal en el control de glucosa en sang. Valors alts de glucosa en la sang mantinguts en el temps afecten negativament la salut, provocant complicacions de diversa índole. És per això que els pacients amb diabetis mellitus tipus 1 necessiten rebre insulina de forma exògena. Des que s'aconseguís en 1921 aïllar la insulina per a poder utilitzar-la en clínica humana, i es començaren a desenrotllar les primeres tècniques de monitorització de glucèmia, s'han produït grans avanços en el tractament amb insulina. Actualment, les línies d'investigació que s'estan seguint en relació a la millora de la qualitat de vida dels pacients diabètics, tenen fonamentalment 2 vessants: un primer que es centra en la investigació de cèl.lules mare per a la reposició de les cèl.lules beta i un segon vessant de caràcter més tecnològic. Dins d' aquest segon vessant, estan obertes diverses línies d'investigació, entre les que es troben el desenrotllament de nous anàlegs d'insulina que permeten emular més fidelment la secreció del pàncrees, el desenrotllament de monitors continus de glucosa no invasius, bombes d'insulina capaces d'administrar distints perfils d'insulina i la inclusió de sistemes d'ajuda a la decisió i telemedicina. El major repte al què s'enfronten els investigadors és el d'aconseguir desenrotllar un pàncrees artificial, és a dir, desenrotllar algoritmes que permeten disposar d'un control automàtic de la glucosa. La principal barrera que es troba per a aconseguir un control rigorós de la glucosa és l'alta variabilitat que presenta el seu metabolisme. Açò és especialment significatiu durant la compensació dels menjars. Aquesta variabilitat junt amb el retard en l'absorció i actuació de la insulina administrada de forma subcutània afavorix l'aparició d'hipoglucèmies tardanes (complicació aguda més important del tractament amb insulina) a conseqüència de la sobreactuació del controlador. Les propostes presentades en aquest treball fan especial insistència en suportar aquestes dificultats. Així, s'utilitzen models intervalares per a representar la fisiologia del pacient, i poder tindre en compte la incertesa en els seus paràmetres. Aquest tipus d'estratègia s'ha utilitzat tant en la proposta de dosificació automàtica en llaç obert com en l' algoritme en llaç tancat. A més, la principal idea de disseny d'aquesta última proposta és evitar la sobreactuació del controlador evitant hipoglucèmies i afegint robustesa. / Revert Tomás, A. (2015). Robust strategies for glucose control in type 1 diabetes [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/56001

Diabetes mellitus is a chronic disease affecting millions of people worldwide. The degenerative changes caused by diabetes can, however, be controlled through the correct treatment. The outcome of diabetes mellitus depends mainly on the patient's self-management. Health professionals therefore have a major responsibility to assist patients to acquire the essential knowledge, skills and attitudes for self-management. The purpose of this study was to identify diabetic patients and family members' knowledge and views about diabetes mellitus and its treatment regimen. A quantitative descriptive survey design was used. Questionnaires were used to collect data from a convenient sample of diabetic patients and family members. Data was analysed by a computer program called Statistical Package for Social Sciences. Findings revealed that patients and family members lack adequate knowledge on diabetes mellitus and its treatment. Recommendations regarding the required information and assistance to be given to diabetic patients and their family members were formulated. / Health Studies / (MA (Health Studies))

Blood glucose management in Type 1 diabetes is crucial in preventing several diabetic complications. Blood glucose management is a complex task requiring diabetics too carefully administer the correct dosages of insulin by taking their blood glucose levels, food consumption, exercise, stress, illnesses and several other factors into account. Improved bolus calculation greatly aids in controlling blood glucose levels within a tight range. This study investigates how the ets-concept (Equivalent Teaspoons Sugar-concept) can be used to develop products to calculate insulin boluses. A cellular phone based software application was developed to calculate insulin boluses using the ets-concept. This product was tested in a clinical trial. A blood glucose characterization procedure was also developed to characterize the blood glucose response of a Type 1 diabetic to carbohydrate ingestion and insulin administration. The characterization procedure was used during the clinical trial to characterize patients in order to customize the bolus calculation products for the specific diabetic user. / Thesis (Ph.D. (Mechanical Engineering)--North-West University, Potchefstroom Campus, 2006

The correct administration of insulin is a constant challenge for type 1 diabetics. The correct insulin regime leads to fewer complications and an easier way of life. The amount of insulin administered must take into account the meals eaten, previous administered insulin, exercise etc. A rapid process for determining insulin regimes that is accessible to type 1 diabetics will greatly reduce diabetic complications later in life. This study researches such a process. Software is developed to use the ets-concept to simulate blood glucose levels. From these simulations blood glucose characterisation can be done to propose insulin regimes. Data gathered in previous studies is used to verify the results of this process. These results are compared to factors that describe the accuracy of a person's blood glucose control. The effects the new regimes will have are used to make recommendations to the end-user. Accurate characterisation leads to insulin regImes that will Improve the control performance of type 1 diabetes. / Thesis (M.Ing. (Electronical Engineering)--North-West University, Potchefstroom Campus, 2008.

Blood glucose management in Type 1 diabetes is crucial in preventing several diabetic complications. Blood glucose management is a complex task requiring diabetics too carefully administer the correct dosages of insulin by taking their blood glucose levels, food consumption, exercise, stress, illnesses and several other factors into account. Improved bolus calculation greatly aids in controlling blood glucose levels within a tight range. This study investigates how the ets-concept (Equivalent Teaspoons Sugar-concept) can be used to develop products to calculate insulin boluses. A cellular phone based software application was developed to calculate insulin boluses using the ets-concept. This product was tested in a clinical trial. A blood glucose characterization procedure was also developed to characterize the blood glucose response of a Type 1 diabetic to carbohydrate ingestion and insulin administration. The characterization procedure was used during the clinical trial to characterize patients in order to customize the bolus calculation products for the specific diabetic user. / Thesis (Ph.D. (Mechanical Engineering)--North-West University, Potchefstroom Campus, 2006

The correct administration of insulin is a constant challenge for type 1 diabetics. The correct insulin regime leads to fewer complications and an easier way of life. The amount of insulin administered must take into account the meals eaten, previous administered insulin, exercise etc. A rapid process for determining insulin regimes that is accessible to type 1 diabetics will greatly reduce diabetic complications later in life. This study researches such a process. Software is developed to use the ets-concept to simulate blood glucose levels. From these simulations blood glucose characterisation can be done to propose insulin regimes. Data gathered in previous studies is used to verify the results of this process. These results are compared to factors that describe the accuracy of a person's blood glucose control. The effects the new regimes will have are used to make recommendations to the end-user. Accurate characterisation leads to insulin regImes that will Improve the control performance of type 1 diabetes. / Thesis (M.Ing. (Electronical Engineering)--North-West University, Potchefstroom Campus, 2008.

Diabetes mellitus is a chronic disease affecting millions of people worldwide. The degenerative changes caused by diabetes can, however, be controlled through the correct treatment. The outcome of diabetes mellitus depends mainly on the patient's self-management. Health professionals therefore have a major responsibility to assist patients to acquire the essential knowledge, skills and attitudes for self-management. The purpose of this study was to identify diabetic patients and family members' knowledge and views about diabetes mellitus and its treatment regimen. A quantitative descriptive survey design was used. Questionnaires were used to collect data from a convenient sample of diabetic patients and family members. Data was analysed by a computer program called Statistical Package for Social Sciences. Findings revealed that patients and family members lack adequate knowledge on diabetes mellitus and its treatment. Recommendations regarding the required information and assistance to be given to diabetic patients and their family members were formulated. / Health Studies / (MA (Health Studies))

Type 2 diabetes mellitus (T2DM), presents a significant health burden globally, affecting millions of individuals, especially in the elderly population. While its association with cardiovascular diseases and cognitive impairments is well-documented, further research on the precise influence of glucose control on cognitive outcomes in elderly T2DM patients is necessary. This scoping review aims to address this gap by investigating the impact of HbA1c levels representing glycemic control on the risk of developing cognitive impairments in elderly patients with T2DM. A literature search was conducted on MEDLINE and eligible studies involved T2DM patients aged 60 or older, with documented cognitive function and glycemic status. Screening and selection processes were conducted following PRISMA guidelines, and three relevant articles were selected for review. Most of the findings suggest a possible association between higher HbA1c levels and cognitive decline. Such results provide valuable insights regarding medical approaches focusing on glucose control that could be created to prevent and delay cognitive decline in T2DM patients.

El presente proyecto nace de la búsqueda de una solución que brinde atención médica remota a los adultos mayores diagnosticados con Diabetes tipo 2, con el fin de mantener un control periódico de su enfermedad y poder reducir las complicaciones presentadas por el incumplimiento del tratamiento médico y control glucémico. La solución consiste en una plataforma tecnológica que soporta una aplicación móvil para el paciente que controla de forma autónoma su enfermedad a través de información sobre la Diabetes, medicamentos, detalle del tratamiento recomendado por el médico y el control periódico del nivel de glucosa. Y una página web permite al endocrinólogo realizar el seguimiento del paciente y videollamadas periódicas. El proyecto se validó en una casa de reposo para adultos mayores y con un médico endocrinólogo en Lima, Perú. Para medir la efectividad del proyecto se evaluó lo siguiente: Constancia del registro del nivel de glucosa Tiempo promedio de respuesta ante emergencias e indicadores fuera de rango, por parte del médico Porcentaje de reducción de las complicaciones de la enfermedad Nivel de satisfacción, de los adultos mayores, sobre la solución de Telehomecare Los resultados demuestran que la frecuencia del uso de la aplicación se incrementó conforme adoptaron la solución como parte de su rutina. El tiempo de respuesta promedio del endocrinólogo fue 4,13 minutos aproximadamente desde su registro, el porcentaje de complicaciones se redujo en un 14% y el nivel de satisfacción de la solución se concentró en las dimensiones de tiempo de respuesta y comprensión de la necesidad del usuario / This project begins to seek a solution that provides remote medical care to older adults diagnosed with Type 2 Diabetes Mellitus, in order to maintain periodic control of their disease and to reduce the complications presented by non-compliance medical treatment and glycemic control. The solution consists in a mobile application for the patient that controls his disease through information related to diabetes, medications, details of the treatment recommended by the doctor and the periodic monitoring of glucose level. Another application allows the endocrinologist to monitor the patient and make periodic video calls. The project was validated in a nursing home for the elderly and with an endocrinologist in Lima, Peru. To measure the effectiveness of the project, the following was evaluated: Record of glucose level record Average response time to emergencies and indicators out of range, by the doctor Percentage reduction in complications of the disease Level of satisfaction, of the elderly, about the Telehomecare solution The results show that the frequency of use of the application increased as they adopted the solution as part of their routine. The average response time of the endocrinologist was approximately 4.13 minutes from its registration, the percentage of complications was reduced by 14% and the level of satisfaction with the solution was concentrated in the dimensions of response time and understanding of patient need. / Tesis