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1
PEROTTI, MARIO. « EFFICACIA DEL PASSAGGIO A DEGLUDEC DA UN’ALTRA INSULINA BASALE (GLARGINE/ DETEMIR) IN UNA COORTE DI PAZIENTI CON DIABETE MELLITO TIPO 1 ( DMT1) IN CONDIZIONI DI REALE PRATICA CLINICA ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241121.
Texte intégralRésumé :
La terapia del diabete tipo 1 può oggi essere più flessibile e personalizzata grazie alla disponibilità di numerosi tipi di insulina che differiscono tra loro per la farmacocinetica (inizio, picco e durata di azione). Il miglior controllo glicometabolico può essere ottenuto attraverso una terapia multiniettiva secondo uno schema basal-bolus, il quale prevede 3 somministrazioni preprandiali di un analogo rapido, che esprime meglio la fisiologica secrezione insulinica determinata dai pasti e da 1 iniezione di insulina ad azione lenta, necessaria per rispondere al fabbisogno insulinico nei periodi di digiuno (interprandiale e notturno).
Il raggiungimento di un controllo glicemico ottimale mediante trattamento insulinico intensivo determina un riduzione del rischio di complicanze micro e macrovascolari, ma conduce inevitabilmente a un incremento dell’incidenza di ipoglicemie, con conseguenze potenzialmente negative per il sistema cardiovascolare e neurologico.
Ottimizzare la terapia farmacologica mediante l’utilizzo di nuovi analoghi dell’insulina ad azione lenta in grado di offrire un minore rischio di ipoglicemia rappresenta un punto di fondamentale importanza.
Insulina degludec presenta molte delle caratteristiche che definiscono il profilo ideale di un’insulina basale. Dopo la somministrazione nel sottocute, grazie alla particolare ingegneria chimica, degludec viene assorbita in modo continuo e uniforme con un effetto ipoglicemizzante stabile e una durata di azione che supera le 42 ore. Dopo circa tre giorni di terapia è possibile raggiungere lo steady state condizione farmacocinetica in cui i livelli circolanti di insulina si mantengano stabili riducendo così la variabilità day-to day
L'utilizzo di degludec è stato ampiamente analizzato nel corso di studi clinici randomizzati ( RCT) sia in pazienti con diabete mellito tipo I sia in pazienti con diabete mellito tipo II. I risultati mostrano una non inferiorità di degludec rispetto a glargine in termine di target glicemici, ma una superiorità di degludec rispetto a glargine in termini di riduzione degli episodi di ipoglicemia soprattutto notturni. Tuttavia il contesto clinico di uno studio randomizzato può non essere completamente riproducibile nella pratica clinica quotidiana. Obiettivo di questo studio retrospettivo è la valutazione dell’efficacia clinica di degludec in una coorte di pazienti affetti da diabete mellito tipo 1 precedentemente trattati con diverso analogo lento ( glargine o detemir) nella pratica clinica quotidiana di real-life.
I risultati di questo studio mostrano un impatto positivo di degludec nella gestione terapeutica di pazienti con diabete mellito tipo 1 in linea con precedenti studi clinici randomizzati . Il passaggio a degludec da un altro analogo basale ( glargine o detemir) è in grado di migliorare il controllo glicemico, con una riduzione media dei valori di HbA1c di 0,20 % [-0,24;-0.17] a 6 mesi rispetto al basale (p <0.001). Inoltre i dati descritti in questo lavoro hanno evidenziato una riduzione del rischio di ipoglicemia sia totale ( rate ratio 0,79 [0,69: 0,89]), sia notturna (rate ratio 0,54 [0,42; 0,69]) sia grave (rate ratio 0,15 [0,09; 0,24]) a 6 mesi dalla modifica di terapia (p <0.001). Tale significatività rimane per tutto il periodo di follow-up di 12 mesi. Infine dopo 6 mesi di terapia con degludec, la dose totale di insulina giornaliera è diminuita del 11% rispetto al basale (p <0,001). Sulla base di questi dati, possiamo affermare che la terapia insulinica con degludec rappresenta un valido strumento terapeutico nella pratica clinica quotidiana, in grado di migliorare il compenso glicemico e la qualità di vita dei pazienti, favorendo così il raggiungimento di obiettivi glicemici più ambiziosi.Type 1 diabetes (DMT1) leads to absolute insulin deficiency due to immunologic destruction of the islet cells. Therefore affected patients need lifelong insulin treatment. Newer therapies for type 1 diabetes are aimed at developing insulin delivery systems that mimick normal physiology, identifying newer insulins that mimick endogenous insulin. To reproduce physiologic insulin secretion, both long- and short-acting insulins are used. Long-acting insulin, given at bedtime, suppresses glucose output from the liver overnight and provides basal insulin between meals; bolus doses of short-acting insulin modulate glucose excursions associated with carbohydrate consumption. Optimal glycemic control is necessary to reduce the risk for diabetes complications. However, tight glucose control carries a risk for hypoglycemia. Hypoglycemia may accelerate the vascular complications of diabetes by increasing platelet aggregation, leading to higher cardiovascular risk and all-cause mortality. Even brief hypoglycemia can cause profound dysfunction of the brain. Insulin administration by subcutaneous route has intrinsic limitations that, together with the pharmacokinetic (PK) profile of insulin formulations, do not reproduce the physiological patterns of insulin secretion. Insulin degludec (IDeg) is an ultra-long insulin analog that has unique pharmacokinetic and pharmacodynamic properties with a half-life of more than 24 h and a duration of action of more than 42 h. Compared to insulin glargine , the insulin degludec glucose-lowering action at steady state shows four time lower day-to day variability. Randomized clinical studies of degludec have shown a reduction in nocturnal hypoglycemia compared to insulin glargine. Given this background, IDeg is an ultra-long insulin analog that exhibits low intra-individual variability and whose efficacy is comparable to IGlar, but which presents as advantages flexibility in dose timing and lower risk of hypoglycemia, benefits that may impact quality of life and adherence to therapy. In Europe data on the use or effect of degludec in the general diabetes population not exist yet. Thus collection of data under routine clinical practice is highly warranted in order to access the effectiveness of degludec in real-life clinical setting. Aim of this retrospective non interventional study is to evaluate the clinical effectiveness of switching to IDeg in insulin treated patients with DMT1 under condition of routine clinical care. In all patients (n: 900), basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. HbA1c decreased by -0.20 % [-0.24; -0.17%] at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.
2
Conterato, Elisabete Viera. « Níveis de leptina, taxa metabólica basal e resistência insulínica em crianças obesas púberes ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/129680.
Texte intégralRésumé :
Introdução: A obesidade infanto-juvenil é um problema de saúde pública, com alta endemia e prevalência crescente no mundo todo. É uma doença associada a significativos problemas de saúde na população pediátrica, que afeta principalmente os sistemas cardiovascular e o endócrino, com risco elevado de desenvolvimento de diabetes mellitus tipo 2, hipertensão arterial, aterosclerose e dislipidemias. Objetivo: Investigar a relação entre os níveis séricos de leptina, a taxa metabólica basal e a resistência insulínica com o escore Z do índice de massa corporal de crianças púberes com obesidade. Métodos: Trata-se de um estudo transversal, realizado com 37 crianças obesas púberes de 7 a 12 anos de idade, atendidas pela primeira vez no Ambulatório de Obesidade Infantil, entre junho/2013 a abril/2014. Os participantes foram submetidos à avaliação antropométrica, aferição da pressão arterial, auto-classificação da maturação sexual, testes laboratoriais e bioimpedância. Resultados: O peso, o índice de massa corporal e a leptina diferiram de modo significativo entre os grupos (grupo 1 indivíduos com obesidade (2 Introduction: Childhood and adolescent obesity is a public health problem that presents high endemic and growing prevalence worldwide. It is a disease associated with important health problems in the population of children, that affects mainly the cardiovascular and endocrine systems, with high risck of developing type 2 diabetes mellitus, arterial hypertension, atherosclerosis and dyslipidemia. Objective: This study aims to investigate the relationship between the serum levels of leptin, the basal metabolic rate and the insulin resistance, with the Z score of the body mass index of children with obesity. Methods: This is a transversal study and 37 obese children, aged between 7 to 12 years old, were treated for the first time in the outpatient care unit specialized in childhood obesity, from June/2013 to April/2014. The participants were submitted to anthropometric evaluation, blood pressure measurement, selfclassification of sexual maturity, laboratory tests and bioimpedance. Results: Weight, body mass index and leptin differed significantly between the groups (Group 1 - individuals as obese (2
3
Jaén, Sitges Maria Luisa. « Terapia génica para la diabetes tipo I basada en la administración intramuscular de AAV1 insulina-glucoquinasa ». Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458687.
Texte intégralRésumé :
La diabetes tipo 1 es una enfermedad metabólica compleja para la cual actualmente no hay cura y está asociada con complicaciones secundarias graves, causadas en gran parte por un control glucémico deficiente. El logro de la normoglucemia con el tratamiento exógeno con insulina requiere el uso de altas dosis de la hormona, lo que aumenta el riesgo de episodios hipoglucémicos potencialmente mortales. En nuestro laboratorio se ha demostrado previamente que una única administración intramuscular de dos vectores AAV de serotipo 1 (AAV1) que expresaban insulina y glucoquinasa produjo corrección de la enfermedad en perros diabéticos durante 4 años. La primera parte de este trabajo se centró en la evaluación de la eficacia y seguridad tras 8 años de tratamiento. Los perros tratados contrarrestaron la hiperglucemia sin necesidad de insulina exógena durante un período de al menos 8 años después de una única administración de los vectores terapéuticos. La normalización metabólica sostenida se demostró mediante la cuantificación plurianual de los niveles séricos de proteínas glucosiladas (fructosamina), triglicéridos y colesterol y la buena respuesta de los animales tratados a la prueba oral de tolerancia a la glucosa. La persistencia de los genomas virales así como la expresión y actividad de los transgenes terapéuticos se atestiguaron en múltiples muestras de los músculos tratados. Además, no se observaron signos de patología en el análisis histopatológico de los mismos. En la segunda parte, se generaron vectores AAV duales que codificaban conjuntamente insulina y glucoquinasa. La generación de un vector dual, permitirá incrementar la eficacia terapéutica de la aproximación ya que todas las células modificadas genéticamente expresarán los dos componentes del “sensor de glucosa”. Asimismo, permite disminuir la dosis viral lo que, por un lado, minimiza la potencial toxicidad, y por otro, facilita los procesos de producción y regulatorios requeridos para una futura aplicación clínica. Los vectores duales mostraron mayor eficacia que la combinación de sus respectivos controles individuales. De entre los diferentes vectores duales con diversas conformaciones y combinaciones de secuencias codificantes y reguladoras generados, el vector con las dos unidades transcripcionales en conformación opuesta medió mayor expresión de los transgenes terapéuticos. Además, entre los vectores generados, el vector “L” (AAV1-miniCMV-hIns-RSV-hGck) fue el que mostró una expresión in vitro más alta tanto de insulina como de glucoquinasa. Los datos en los estudios realizados en ratones diabéticos tratados con el vector dual confirmaron una eficacia superior a la obtenida en los ratones tratados con los vectores individuales. Por tanto, los datos obtenidos en esta tesis doctoral demuestran la eficacia y seguridad a largo plazo de la administración intramuscular de los vectores AAV que codifican para insulina y glucoquinasa para contrarrestar la diabetes y sientan las bases para la futura translación a la clínica de esta estrategia terapéutica.Diabetes is a complex metabolic disease for which there is currently no cure and is associated with severe secondary complications, caused largely by poor glycaemic control. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We previously demonstrated that a single intramuscular administration of two AAV serotype 1 (AAV1) vectors expressing insulin and glucokinase produce 4 years of disease correction in diabetic dogs. The first part of this study focused on the evaluation of efficacy and safety after 8 years of treatment. It is demonstrated how these dogs maintain glycemic control without the need of exogenous insulin for a period of up to 8 years after a single administration of the therapeutic vectors. Long term metabolic normalization was demonstrated by the multi-annual quantification of serum levels of glycosylated proteins (fructosamine), triglycerides and cholesterol and the correct response of the treated animals to the oral glucose tolerance test. The persistence of the viral genomes and the expression and activity of the therapeutic transgenes were confirmed in multiple samples of the treated muscles. In addition, no signs of pathology were observed in the histopathological analysis of the same muscles. In the second part of the study, dual AAV1 vectors were generated that encoded together insulin and glucokinase. The generation of a dual vector will allow to increase the therapeutic efficacy since all the genetically modified cells will express the two components of the "glucose sensor", while a reduced viral dose with minimize potential toxicity, and simplify both the production and regulatory processes required for future clinical application. The design of the modular system allowed for the generation and evaluation of conformations and combinations of coding and regulatory sequences. These were evaluated in vitro to demonstrate that the dual vectors with the two units in opposite conformation mediated a greater expression of both transgenes. The data in the studies performed in healthy and diabetic mice administered with the dual vectors confirmed that efficacy was superior to that obtained in the mice treated with the individual vectors. Therefore, the data obtained in both parts of this work demonstrate the long-term functionality and safety of intramuscular administration of AAV1 vectors encoding insulin and glucokinase to counteract diabetes while providing the basis for future clinical translation of a this type of gene therapy strategy, using a single dual AAV1 vector expressing both genes.
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Oak, Mayura Arvind. « Controlled Delivery of Basal Level of Insulin ». Diss., North Dakota State University, 2013. https://hdl.handle.net/10365/26761.
Texte intégralRésumé :
The present study was aimed at developing a delivery system for controlled release of insulin at basal level from chitosan-zinc-insulin complex incorporated into thermosensitive polymer, poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA). Chitosan-zinc-insulin complex was optimized to restrict the insulin diffusion from the delivery system by complex formation and thereby reducing initial burst release. Polymer concentration, insulin loading, chitosan and ZincNational Institutes of Health (NIH)
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Ashwell, Simon Guy. « New approaches to basal insulin therapy in diabetes ». Thesis, University of Newcastle upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413268.
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Capel, Flores Ismael. « Validación clínica inicial de un sistema de páncreas artificial con controlador basado en reglas ». Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457142.
Texte intégralRésumé :
La diabetes mellitus tipo 1 implica una deficiencia completa de la secreción nativa de insulina y su tratamiento fundamental, hasta la fecha, es la sustitución de esta secreción con insulina exógena de la forma más fisiológica posible. Los tratamientos actuales son imperfectos y necesitan ser optimizados. En este sentido, la integración de sensores continuos de glucosa con algoritmos que decidan la dosis óptima de insulina a administrar y bombas de infusión continua subcutánea de insulina, constituyendo un sistema de páncreas artificial, puede suponer una mejoría muy significativa de las opciones terapéuticas disponibles hasta el momento. Se han propuesto diferentes algoritmos de control para páncreas artificial pero no existe un gold standard. El Grupo de Bioingeniería y Telemedicina de la Universidad Politécnica de Madrid junto al Servicio de Endocrinología del Hospital Universitari Parc Taulí han desarrollado un algoritmo para páncreas artificial denominado Predictive Rule-Based Algorithm (pRBA). Este algoritmo parte de la pauta de insulina habitual, con bomba de infusión continua, del paciente y le aplica una serie de reglas que optimizan continuamente la dosis en base a la predicción que realiza una red neuronal artificial. Se trata de un sistema híbrido que automatiza totalmente el control basal o nocturno pero que requiere de aviso de las ingestas.
El objetivo principal de la investigación expuesta en esta tesis doctoral fue la validación clínica inicial, en medio hospitalario, del controlador pRBA. Para ello se ha llevado a cabo un ensayo clínico aleatorizado y cruzado en el que 10 pacientes con diabetes tipo 1 han pasado 2 noches no consecutivas en el hospital; una con su pauta habitual de bomba (noche control) y otra bajo el control del pRBA (noche experimental). El periodo de control automatizado fue de las 22:00 a las 10:00h del día siguiente, incluyendo el control nocturno y el control prandial del desayuno. El contralador pRBA ha demostrado que es capaz de mantener a los pacientes mayor tiempo en glucemia objetivo (3,9-8,0 mmol/l) durante el periodo nocturno (00:00-08:00h) que la pauta de tratamiento habitual (95,8 % [73-100] versus 66.6% [8,3-75]; p<0,05). Así mismo ha demostrado conseguir un menor porcentaje de tiempo en hipoglucemia (<3,9 mmol/l) en el mismo periodo (0,0 [0,0-0,0] versus 4,2 [0,0-21]; p<0,05) y reducir la variabilidad glucémica (HBGI 1,60 versus 3,95; p<0,05). En relación al control prandial del desayuno no se han observado diferencias significativas entre el periodo experimental y control (porcentaje de tiempo entre 3,9-10 mmol/l en el periodo 08:00-10:00h 50,0% [50,0-100] versus 58,3% [29,1-87,5]; p n.s.).
Como conclusión de la investigación expuesta en esta tesis podemos establecer que el controlador pRBA se muestra eficaz y seguro para el control nocturno de pacientes con diabetes tipo 1, pero que no muestra ventajas evidentes para el control prandial. Debe optimizarse el controlador prandial y poder testar el algoritmo en condiciones más reales antes de plantear su uso clínico ordinario.Type 1 diabetes mellitus implies a complete deficiency of native insulin secretion and its fundamental treatment, to date, is the replacement of this secretion with exogenous insulin as physiologically as possible. Current treatments are imperfect and need to be optimized. Integration of continuous glucose sensors with algorithms that decide the optimal dose of insulin to be administered and continuous subcutaneous insulin infusion pumps, constituting an artificial pancreas system, may imply a very significant improvement in the therapeutic options available until the moment. Different control algorithms have been proposed for artificial pancreas but there is no gold standard. Our research team, integrated by Grupo de Bioingeniería y Telemedicina (GBT) - Universidad Politécnica de Madrid, together with the Endocrinology Department of Parc Taulí University Hospital-UAB, has developed an artificial pancreas algorithm called Predictive Rule-Based Algorithm (pRBA). This algorithm starts from the patient's usual insulin regimen, with a continuous infusion pump, and applies a series of rules that continuously optimize the dose based on the prediction of an artificial neural network. It is a hybrid system that fully automates basal or night control but requires notification of intakes. The main objective of the research presented in this doctoral thesis was the initial clinical validation, in hospital setting, of the pRBA controller. For this, a randomized and cross-over trial has been carried out in which 10 patients with type 1 diabetes have spent 2 non consecutive nights in the hospital; one with his/her usual pump pattern (night control) and another under the control of pRBA (experimental night). The automated control period lasted from 22:00 to 10:00 on the following day, including night control and prandial breakfast control. pRBA algorithm has been shown to be able to keep patients longer on target glycemia (3.9-8.0 mmol/l) during the night time period (00:00-08:00) than the usual treatment regimen (95.8% [73-100] versus 66.6% [8.3-75], p <0.05). It has also been shown to achieve a lower percentage of time in hypoglycemia (<3.9 mmol/l) in the same period (0.0 [0.0-0.0] versus 4.2 [0.0-21]; p <0.05) and reduced glycemic variability (HBGI 1.60 versus 3.95, p <0.05). Regarding to breakfast prandial control, no significant differences were observed between the experimental and control periods (percentage of time between 3.9-10 mmol/l in the period 08:00-10:00h 50,0% [50,0- 100] versus 58.3% [29.1-87.5]; p ns). As a conclusion of the research exposed in this thesis we can establish that the pRBA controller is shown to be effective and safe for the nocturnal control of patients with type 1 diabetes, but does not show significant advantages for the prandial control. The prandial controller must be optimized and the algorithm should be tested under more real conditions before its usual clinical use is raised.
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Gludsted, Emil Brohl. « A study of value transitions in the basal insulin regimen for treatment of type 2 diabetes ». reponame:Repositório Institucional do FGV, 2016. http://hdl.handle.net/10438/17639.
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Type 2 diabetes is a progressive disease projected to grow tremendously in prevalence. Basal insulin analogues used to be the most efficacious treatment and last step in therapeutic intensification. Today, demographic, economic and epidemiologic transitions have placed pressure on healthcare systems and payers’ budgets. Three imminent threats require the basal insulin regimen to rethink how value can be addressed in the market: mounting institutional pricing pressure, biosimilar competition and, new innovative anti-diabetic drug classes with the potential to delay insulinization. Products aspiring to compete in the basal insulin regimen must avoid commoditization and steer clear of new threats. This paper identifies seven strategies and tactics to successfully address value in the diabetes market and particularly in the basal insulin regimen: 1) cost-based advantage and price competition; 2) value-based pricing; 3) risk-sharing agreements; 4) redifferentiation and post-approval evidence generation; 5) combination products carrying complementary mechanisms of action; 6) treating comorbidities and adjacent diseases; and, 7) indicating for patient sub-populations.
A diabetes tipo 2 é uma doença progressiva cuja projeção é crescer tremendamente em prevalência. Análogos de insulina basal eram considerados o tratamento mais eficaz, e utilizados em último instância durante a intensificação terapêutica. Hoje, transições demográficas, econômicas e epidemiológicas tem colocado pressão nos sistemas de saúde e no orçamento dos usuários. Três iminentes ameaças levam o regime de insulina basal à necessidade de repensar a maneira como seu valor é apresentado ao mercado: crescente pressão institucional sobre os preços, competição de biosimilares e novas classes medicamentos inovadores anti-diabetes com o potencial de atrasar a insulinização. Produtos que buscam competir no regime de insulina basal devem evitar a comoditização e esquivar-se de novas ameaças. Este trabalho identifica sete estratégias e táticas para apresentar de maneira bem sucedida valor no mercado de diabetes e particularmente no regime de insulina basal: 1) vantagem baseada em custo e competição por preço; 2) precificação baseada em valor; 3) acordos de compartilhamento de riscos; 4) rediferenciação e geração de evidencias pós-aprovação; 5) produtos combinados que apresentam mecanismos complementares de ação; 6) tratamento de co-morbidades e doenças adjacentes; e, 7) indicação para pacientes de determinados sub-grupos da população.
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Barrault, Valérie. « Les protéines kinases C : mise au point du dosage et valeurs basales dans divers modèles expérimentaux ». Paris 5, 1992. http://www.theses.fr/1992PA05P083.
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Sharma, Divya. « Drug Delivery Systems for Treatment of Diabetes Mellitus ». Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/31745.
Texte intégralRésumé :
Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications.
Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes.National Institutes of Health (NIH) grant R15GM114701
ND EPSCoR seed award FAR0030636
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Fujimoto, Shinpei. « Augmentation of basal insulin release from rat islets by preexposure to a high concentration of glucose ». Kyoto University, 2001. http://hdl.handle.net/2433/150511.
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Moolman, Lukas Johannes. « The effect of snacking on continuously monitored glucose concentrations in analogue insulin basal bolus treatment regimens ». Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/40694.
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Potier, Grégory Brouard-Orzechowski Christine. « Évaluation d'une cohorte d'enfants diabétiques de type I traités selon un schéma basal-bolus en relais d'un schéma conventionnel ». Créteil : Université de Paris-Val-de-Marne, 2006. http://doxa.scd.univ-paris12.fr:80/theses/th0248495.pdf.
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Van, der Westhuizen Johan Albert. « A novel blood glucose characterisation system for type 1 diabetes / Johan Albert van der Westhuizen ». Master's thesis, North-West University, 2008. http://hdl.handle.net/10394/4186.
Texte intégralRésumé :
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.
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Cortinas, Abel Bryan. « Design, synthesis, and evaluation of insulin bioconjugates for the application of enhanced basal and glucose-responsive activity ». Thesis, Massachusetts Institute of Technology, 2018. https://hdl.handle.net/1721.1/121809.
Texte intégralRésumé :
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2018Cataloged from PDF version of thesis.
Includes bibliographical references (pages 132-143).
Since its discovery by Banting and Best, the administration of exogenous insulin to control blood glucose levels has been a primary method of treatment for severe cases of diabetes mellitus. Several decades of insulin engineering and development has led to the clinical introduction of two broadly classified categories of protein therapies: prandial and basal insulins. Although these developments have had profound effects on disease management with respect to insulin-dependent diabetes, the overall strategy for development has historically been restricted to rational design criteria based on static pharmacodynamic profiles, profiles that are inherently naive to physiological changes in the diabetic patient. As a result, stringent patient-dependent regimens are the standard of care with regard to glycemic monitoring and management.
When coupled with issues such as patient noncompliance, severe hypoglycemia, as well as the adverse health effects that result from chronic mismanagement of hyperglycemia, it is obvious that there are still major hurdles that must be overcome to properly treat the disease. Herein, we introduce innovative strategies aimed towards the advancement of novel insulin bioconjugate design and development for enhanced long-term efficacy and glucose-responsive activity. First, we develop a class of unimolecular, glucose-responsive insulin conjugates towards the design of a state-responsive, patient-dependent therapy.
Optimization of this system resulted in the identification of a lead candidate, lns-PL-4FPBA, capable of (1) glucose-mediated changes in solubility for long-term sequestration and intelligent depot formation, (2) superior safety in comparison to clinically used long-acting insulins, and (3) glucose-responsive pharmacokinetic and pharmacodynamic activity in both healthy and diabetic animal models. Next, we pioneer the first design and synthesis strategy of a novel class of sugar-responsive insulin conjugates, with the ultimate goal of developing an insulin bioconjugate capable of sugar-mediated receptor binding interactions. In this effort, we created dynamically cyclized insulin conjugates that were found to exhibit enhanced chemical stability and superior thermal stability relative to the native protein, as well as sugar-mediated destabilization, suggesting the potential to exploit the insulin receptor binding mechanism.
Lastly, we focus on improving basal activity of the insulin protein by utilizing a novel class of zwitterionic insulin polymer conjugates towards the generation of ultra long-acting insulin therapies. The resulting library is demonstrated to afford equivalent biological potency relative to native human insulin, augmented thermal and chemical stability capable of withstanding thermal aggregation for over 80 days, as well as ultra long-acting basal insulin potential.
by Abel Bryan Cortinas.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemical Engineering
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Pelzer, Ruaan. « A new approach to improving the control of type 1 diabetes / Ruaan Pelzer ». Phd thesis, North-West University, 2006. http://hdl.handle.net/10394/4167.
Texte intégralRésumé :
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
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Perrin, David Péquignot Jean-Marc. « Caractérisation de la balance énergétique et de son contrôle monoaminergique central et périphérique chez un modèle de rat ne développant pas d'obésité, le rat Lou/C ». [s.l.] : [s.n.], 2003. http://tel.archives-ouvertes.fr/docs/00/06/93/19/PDF/fulltextDP.pdf.
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Guerra, Perrin Yannis Sergio. « Inpatient basal bolus regimens| Insulin Glargine/Lispro versus Insulin NPH/Regular. Retrospective comparison of hypoglycemic rates and glucose control, and the differential effect of non-clinical temporal factors on them ». Thesis, Rush University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=1523752.
Texte intégralRésumé :
Objective: Inpatient protocols for glycemic control
Research Design and Methods: This retrospective observational study analyzed the adult admissions to a Teaching Hospital from October 2010 to February 2013. The association between the protocol using insulin Glargine/Lispro vs NPH/regular and rates of hypoglycemia (glucose ≤ 70 mg/dl), severe hypoglycemia (≤ 550 mg/dl), severe hyperglycemia (≥ 300 mg/dl), and average glucose per patient-day were evaluated. The effect on these outcomes of being hospitalized on the week/weekend and the personnel shift (7-3, 3-11, 11-7) were also analyzed.
Results: The rates of hypoglycemia (severe or not) were lower in the analog insulin protocol after multivariate logistic modeling. The rate of hyperglycemia was higher on the analog insulin protocol, but this association disappeared after multivariate modeling. The outcomes were not affected by the weekend, but the rate of hypoglycemia was lower in the 3-11 shift, and the rate of hyperglycemia was lower in the 11-7 shift.
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Schetzina, Karen E. « Use of Basal‐Bolus Insulin Therapy at Time of Diagnosis of Type 1 Diabetes Mellitus in Pediatric Patients Provides Improved 1st Year Glycemic Control Compared to Conventional NPH Regimens ». Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/5124.
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Hunnisett, Douglas J. « Leptin demonstrates no significant effect on basal or insulin-stimulated 2-deoxyglucose uptake and C¹§4-labelled glucose incorporation into glycogen in L6 myotubes ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0024/MQ50346.pdf.
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Burke, Rebecca M. « Bone morphogenetic protein 9 and insulin-like growth factor 2 modulate the cholinergic phenotype of the basal forebrain cholinergic system : relevance to aging and Alzheimer's disease ». Thesis, Boston University, 2012. https://hdl.handle.net/2144/12300.
Texte intégralRésumé :
Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The basal forebrain cholinergic neurons (BFCN), whose projections terminate in the cortex and hippocampus, are critically important for the processes of learning, memory, and attention. BFCN degeneration occurs with age and in Alzheimer's disease, and correlates with the cognitive decline observed in these states. Multiple stimuli, including growth factors, control the development, differentiation, and maintenance of the BFCN population. Specifically, bone morphogenetic protein 9 (BMP9/GDF2) increases acetylcholine (ACh) synthesis and choline acetyltransferase (CHAT) gene expression both in vivo and in vitro, and has therefore been characterized as a cholinergic differentiation and maintenance factor. Similarly, insulin-like growth factor 2 (IGF2) induces CHAT activity in an embryonic in vitro model and stimulates ACh release in rat hippocampal slices. Given the ability of BMP9 and IGF2 to promote the cholinergic phenotype, we explored the effects of a one-week intracerebroventricular infusion of BMP9 and IGF2 on the BFCN population in the adult wildtype rat and in the transgenic APPswe/PS1deltaE9 Alzheimer's disease mouse model. Our results revealed that IGF2 increased ACh levels in the frontal cortex of the adult rat by approximately 25%, and increased hippocampal nerve growth factor receptor-p75 protein levels, a marker of cholinergic neurons , by 40%. IGF2 increased the expression of hippocampal insulin-like growth factor 1, a cholinergic differentiation factor, by 26% in the adult rat. Similarly, BMP9 increased hippocampal CHAT protein expression in the 5-month old wildtype and APPswe/PS1deltaE9 mouse by 70% and 40%, respectively. BMP9 also prevented a transgene-mediated decrease in hippocampal CHAT protein levels in the 10-month old APPswe/PS1deltaE9 mouse. Furthermore, BMP9 increased the levels of nerve growth factor (NGF), a trophic factor for cholinergic neurons, in the 5-month old and 10-month old wildtype mouse hippocampus by 15% and 16%, respectively, and increased hippocampal NGF levels by 15% in the 10-month old APPswe/PS1deltaE9 mouse hippocampus. These results indicate that BMP9 and IGF2 promote the cholinergic phenotype and create an environment that is trophic for cholinergic neurons. These actions of IGF2 and BMP9 suggest that they may have therapeutic potential for the treatment of disease states that compromise cholinergic function.
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MILIĆ, Jovana. « Relazioni chiave tra steatosi epatica, insulino-resistenza, diabete mellito, fragilità, terapia antiretrovirale basata sugli inibitori dell'integrasi e aumento di peso nelle persone che vivono con HIV ». Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2021. http://hdl.handle.net/11380/1253896.
Texte intégralRésumé :
Introduzione
La steatosi epatica non alcolica (NAFLD) è diventata una condizione emergente nella popolazione generale che invecchia e la causa più comune di malattia epatica cronica. Abbiamo ipotizzato che NAFLD potrebbe essere un determinante significativo di fragilità, nel contesto di una natura multisistemica di entrambe queste condizioni. L'obiettivo dello studio era quello di indagare la correlazione tra steatosi epatica e fibrosi significativa da sola e in associazione (NAFLD con fibrosi) e fragilità, come misura dell'età biologica, in PLWH.
Metodi
Questo è stato uno studio cross-sectional su pazienti consecutivi che hanno frequentato la Modena HIV Metabolic Clinic nel 2018-2019. Sono stati esclusi i pazienti con assunzione pericolosa di alcol e co-infezione da epatite virale. La steatosi epatica è stata diagnosticata mediante il parametro di attenuazione controllata (CAP), mentre la fibrosi epatica è stata diagnosticata mediante misurazione della rigidità epatica (LSM). NAFLD è stata definita come presenza di steatosi epatica (CAP≥248), mentre fibrosi epatica significativa o cirrosi (stadio ≥F2) come LSM> 7,1 kPa. La fragilità è stata valutata utilizzando un indice di fragilità di 36 elementi (FI). La regressione logistica è stata utilizzata per esplorare i predittori di fragilità utilizzando la steatosi e la fibrosi come covariate.
Risultati
Abbiamo analizzato 707 PLWH (età media 53,5 anni, 76,2% maschi, CD4 mediano 700 μl, 98,7% con HIV RNA non rilevabile). NAFLD con fibrosi era presente nel 10,2%; Il 18,9% e il 3,9% dei pazienti sono stati classificati rispettivamente come fragili e più fragili. L'analisi univariata ha dimostrato che deterioramento neurocognitivo (OR = 5.1, 1.6-15), insufficienza di vitamina D (OR = 1.94, 1.2-3.2), obesità (OR = 8.1, 4.4-14.6), diabete (OR = 3.2, 1.9-5.6) e l'osteoporosi (OR = 0,37, 0,16-0,76) erano significativamente associati a NAFLD con fibrosi. I predittori di FI includevano: steatosi (OR = 2.1, 1.3-3.5), fibrosi (OR = 2, 1-3.7), NAFLD con fibrosi (OR = 9.2, 5.2-16.8), diabete (OR = 1.7, 1-2.7) e multimorbidità (OR = 2,5, 1,5-4).
Conclusione
La steatosi epatica e NAFLD con fibrosi erano associate a fragilità. La NAFLD con fibrosi ha superato la multimorbilità nella previsione della fragilità, suggerendo la prima come indicatore dell'età metabolica nella PLWH.Background Non-alcoholic fatty liver disease (NAFLD) has become an emerging condition in general aging population and the most common cause of chronic liver disease. We hypothesized that NAFLD could be a significant determinant of frailty, in the context of a multisystemic nature of both these conditions. Therefore, the objective of the study was to investigate the correlation between liver steatosis and significant fibrosis alone and in association (NAFLD with fibrosis) and frailty, as a measure of biological age, in PLWH. Methods This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. Patients with hazardous alcohol intake and viral hepatitis co-infection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP≥248), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM>7.1 kPa. Frailty was assessed using a 36-Item frailty index (FI). Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates. Results We analyzed 707 PLWH (mean age 53.5 years, 76.2% males, median CD4 700 μL, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9% and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment (OR=5.1, 1.6-15), vitamin D insufficiency (OR=1.94, 1.2-3.2), obesity (OR=8.1, 4.4-14.6), diabetes (OR=3.2, 1.9-5.6) and osteoporosis (OR=0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of FI included : steatosis (OR=2.1, 1.3-3.5), fibrosis (OR=2, 1-3.7), NAFLD with fibrosis (OR=9.2, 5.2-16.8), diabetes (OR=1.7, 1-2.7) and multimorbidity (OR=2.5, 1.5-4). Conclusion Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.
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Vale, Rodrigo Gomes de Souza. « Modifica??es introduzidas pelos treinamentos cardiopulmonar e neuromuscular nos n?veis s?ricos basais de fatores de crescimento insulina s?mile i (igf-1), cortisol, autonomia funcional e qualidade de vida de mulheres idosas ». Universidade Federal do Rio Grande do Norte, 2009. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13174.
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Made available in DSpace on 2014-12-17T14:13:33Z (GMT). No. of bitstreams: 1
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Previous issue date: 2009-05-15Changes introduced by cardiopulmonar and neuromuscular training on basal serum insulin-like grow factor-1 (IGF-1) and cortisol levels, functional autonomy and quality of life in elderly women The aim of this study was to compare the effects of strength and aerobic training on basal serum IGF-1 and Cortisol levels, functional autonomy (FA) and quality of life (QoL) in elderly women after 12 weeks of training. The subjects were submitted the strength training (75-85% 1-RM) with weight exercises (SG; n=12; age=66.08 ? 3,37 years; BMI=26,77 ? 3,72 kg/m2), aerobic training with aquatic exercises (AG; n=13; age=68,69 ? 4,70 years; BMI=29,19 ? 2,96 kg/m2) and control group (CG; n=10; age=68,80 ? 5,41 years; BMI=29,70 ? 2,82 kg/m2). Fasting blood was analyzed to measure basal IGF-1 and cortisol levels by chemiluminescence method. The t-Student test showed increased IGF-1 in the SG (p<0.05) for intragroup comparison. The Repeated-measure ANOVA presented increased IGF-1 (p<0.05) in the SG compared to the other two groups. There were no differences in cortisol levels. All the FA tests (GDLAM autonomy protocol) presented decreased significant in the time marked in seconds to the SG. The same results were found in the AG, except in the rise from a sitting position test. The autonomy index presented significant improvements (p<0.05) in the SG related to the AG and CG and in the AG to the CG. The SG showed increased QoL (p<0.05) (by WHOQOL-Old questionnaire) in the facet 1 (sensorial functioning) and facet 5 (death and dying). Thus, the SG obtained positive changes on IGF-1 and FA levels when compared to the AG. This suggests that strength training can indicated to decrease the effects of ageing.
O objetivo do estudo foi comparar os efeitos dos treinamentos de for?a e ?bico sobre os n?veis s?ricos basais de IGF-1 e Cortisol, autonomia funcional (AF) e qualidade de vida (QV) em mulheres idosas ap?s 12 semanas de treinamento. Os sujeitos foram submetidos a um treinamento de for?a (75-85% 1-RM) na muscula??o (GF; n=12; idade=66,08 ? 3,37 anos; IMC=26,77 ? 3,72 kg/m2), treinamento aer?bico na hidrogin?stica (GA; n=13; idade=68,69 ? 4,70 anos; IMC=29,19 ? 2,96 kg/m2) e um grupo controle (GC; n=10; idade=68,80 ? 5,41 anos; IMC=29,70 ? 2,82 kg/m2). A coletada de sangue foi feita em jejum para as an?lises dos n?veis de IGF-1 e Cortisol basal (M?todo Quimioluminesc?ncia). O teste t-Student mostrou aumento do IGF-1 no GF (p<0,05) na compara??o intragrupo. A ANOVA de medidas repetidas apresentou eleva??o do IGF-1 (p<0,05) no GF comparado aos demais grupos. Os n?veis de cortisol n?o apresentaram diferen?as. Todos os testes de AF (protocolo de autonomia GDLAM) apresentaram redu??es significativas nos tempos aferidos em segundos para o GF. Os mesmos resultados foram encontrados para o GA, exceto no teste levantar da posi??o sentada. O ?ndice de autonomia apresentou melhoras significativas (p<0,05) do GF para o GA e GC e do GA para o GC. O GF apresentou aumentos significativos (p<0,05) na QV (question?rio WHOQOLOld) nas facetas 1 (habilidade sens?rio) e 5 (morte e morrer). Assim, o GF obteve melhoras significativas nos n?veis de IGF-1 e de AF quando comparado ao GA. Isto sugere que o treinamento de for?a pode ser indicado para minimizar os efeitos delet?rios do envelhecimento
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Perrin, David. « Caractérisation de la balance énergétique et de son contrôle monoaminergique central et périphérique chez un modèle de rat ne développant pas d'obésité, le rat Lou/C ». Phd thesis, Université Claude Bernard - Lyon I, 2003. http://tel.archives-ouvertes.fr/tel-00069319.
Texte intégralRésumé :
Le rat Lou/C ne développe pas d'obésité et est présenté comme un modèle de vieillissement sain. Afin de caractériser la balance énergétique de ces rats, leur adiposité, leur prise alimentaire ainsi que leur dépense énergétique ont été mesurées à 1, 6, 12, 18 et 24 mois en comparaison avec des rats Wistar. Le rôle des monoamines centrales dans la balance énergétique particulière des rats Lou/C a été évalué en mesurant les contenus en monoamines et l'activité des enzymes limitantes de leur synthèse dans les noyaux bulbo-pontiques noradrénergiques, sérotoninergiques et dans les noyaux hypothalamiques. L'activité sympathique a été mesurée dans les tissus périphériques impliqués dans la mise en réserve et la dépense énergétique. Les concentrations plasmatiques de leptine et d'insuline, deux hormones informant les centres de l'état des réserves énergétiques, ont été déterminées au cours du vieillissement chez les deux souches. Le rat Lou/C présente à tous les âges une prise alimentaire inférieure au rat Wistar et une dépense énergétique supérieure à 6 et 12 mois. Les rats Lou/C ont une activité sympathique spécifiquement augmentée dans les tissus adipeux blancs et brun associée à une diminution du profil catécholaminergique central dans certaines structures bulbo-pontiques et dans les noyaux hypothalamiques régulant la balance énergétique. Dès 6 mois, la leptinémie des rats Wistar est supérieure à celle des rats Lou/C. L'insulinémie augmente fortement chez les rats Wistar âgés, alors qu'elle reste stable au cours du vieillissement chez les rats Lou/C. L'absence de résistance à l'insuline chez les rats Lou/C est confirmée par le test euglycémique-hyperinsulinique.
Ainsi, le système nerveux sympathique et le contrôle monoaminergique central sont impliquées dans le déterminisme énergétique du rat Lou/C et cette souche est un modèle de vieillissement sain au regard de sa balance énergétique, de son adiposité, de la résistance à la leptine et à l'insuline
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Yeh, Tzu-Chen, et 葉姿辰. « Hypoglycemic risk and utilization in diabetic population initiating basal insulin treatment ». Thesis, 2009. http://ndltd.ncl.edu.tw/handle/09490296872583742839.
Texte intégralRésumé :
碩士國立臺灣大學
預防醫學研究所
97
Background: The usage of insulin analogue in Taiwan increase in latest years. Recent studies stated that long-acting insulin analogues (LAIA) provide a delayed onset of action and a peakless effect that may be associated with fewer episodes of hypoglycemia than conventional insulin. It might also provide moderation of health utilization and medical cost. However, there is lack of studies in postmarketing comparative effectiveness or health utilization of basal insulins in Taiwan. The aims of this study were to evaluate hypoglycemic risk of different basal insulin and to analyze the utilization from patients newly initiated these agents Besides, we evaluated which factors would influence prescriptions of insulin analogue with propensity score (PS) method. Methods: We conducted a retrospective analysis using National Health Insurance claims data for diabetes newly treated with LAIA or conventional intermediate-long acting insulin (ILI) between July 1, 2004 and December 31, 2006 (n=19075). Eligibility required at least 6 months of insurance before the index prescription date. The PS for receiving LAIA was estimated using logistic regression based on observed characteristics such as patient levels, hospital levels, and diabetes-related costs and utilization. Patients who had at least one hypoglycemic event during this period were extracted (n=930). The first hypoglycemic event was defined as index event. We defined case period as 1-14 days immediately before the event and 3 matched control periods 29-42, 43-56, 57-70 days prior to the index event of the same patient. Exposure to LAIA or ILI during different periods was compared using conditional logistic regression adjusting with time-dependent covariates. n the cohort study, individuals with prescriptions for only insulin detemir (IDet, n=683), insulin glargine (IGlar, n=2961) or ILI(n=13356) were followed until death or the end of study. Utilization of these groups was analyzed with general linear model and post hoc analyses. Results: Part I. The associated factors related to prescribing LAIA were medical centers, clinics, endocrinologists, family physicians, female doctors, metabolic disease, A1c tests, premixed insulin, or diabetes-related outpatient costs. Part II. By using case-crossover approach, recent use of ILI was associated with hypoclycemia. [Odds ratio (OR) = 1.45, p<0.01]. There was no significantlly increasing hypoglycemic risk of LAIA [OR=1.57, p=0.08]. The OR of LAIA over ILI was 1.05 and non-significant (p=0.85). Part III. On average, IDet and IGlar subjects had obviously more outpatient visits and costs, analogues usage, diabetes-related pharmacy costs and A1c tests (p<0.001) but fewer inpatient visits and costs (p<0.001) compared to ILI users. Total medical costs were reduced in analogues users (IDet NT$104769, IGlar NT$103111 vs ILI NT$140413, p<0.001). Conclusion: Subjects newly treated with intermediate-long acting insulin have indeed higher hypoglycemic risk than nonusers of this drug. Owing to fewer subjects of long-acting insulin analogues, we couldn’t confirm that there was no statistical difference of hypoglycemic risk between long-acting insulin analogues and intermediate-long acting insulin. We need to collect more information to prove it in future study. Compared to intermediate-long acting insulin users, long-acting insulin analogues users incurred higher outpatient utilization and diabetes-related pharmacy costs but fewer hospitalizations which led lower total costs. Finally, we should improve quality of care, such as increasing A1c tests, in those patients using intermediate-long acting insulin who have more comorbidities and higher hospitalization rates, thus diabetic complications would be decreased and total medical cost would be reduced thereafter.
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Toney, Scott E. « Effects of basal-bolus insulin correction on inpatient diabetes glycemic control ». 2009. http://proquest.umi.com/pqdweb?did=1913184311&sid=1&Fmt=2&clientId=3916&RQT=309&VName=PQD.
Texte intégralRésumé :
Thesis (M.A.)--Northern Kentucky University, 2009.Made available through ProQuest. Publication number: AAT 1469964. ProQuest document ID: 1913184311. Includes bibliographical references (p. 35-36)
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Haase, Maike. « Vergleich von zwei Protokollen zur Durchführung eines Fastentages zur Überprüfung der basalen Insulinsubstitution bei Typ-1-Diabetes : Konsequentes Fasten im Vergleich zur Erlaubnis einer Kost mit vernachlässigbarem Kohlenhydrat- und Kaloriengehalt ». Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E391-3.
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Chien, Li-Chen Chang, et 張簡麗真. « Comparison of Basal Insulin versus Pioglitazone Added to Oral Agents Therapy for Poor Controlled of Type 2 Diabetes ». Thesis, 2011. http://ndltd.ncl.edu.tw/handle/26750924818506239455.
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碩士高雄醫學大學
藥學研究所碩士在職專班
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Objective For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycemic control, necessitating insulin therapy. Nevertheless, the majority of patients in Taiwan are reluctant to use insulin therapy. American Diabetes Association (ADA) recommended that patients with poor glycemic control while using OADs could also consider adding basal insulin or thiazolidinediones (TZDs) treatment. In the present research, we compared efficacy and safety of the treatment of adding once-daily basal insulin or TZDs in type 2 diabetic patients insufficiently glycemic control by OADs. Methods Pharmacy prescription database from a regional teaching hospital in southen Taiwan were employed in this retrospective study. Type 2 diabetic patients who are insufficiently controlled by OADs (sulfonylurea plus metformin) were designed by adding on either insulin glargine or pioglitazone between January 1 and December 31 of 2008. We compared the changes between baseline and end-point in hemoglobin A1C (HbA1C) and fasting plasma glucose (FPG) for efficacy of the treatment while comparing patients’ body weight changes and their changes in lipid profile (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)), serum creatinine (Scr) and glutamic pyruvic transaminase (GPT) levels for safety of the treatment. Results and Discussion Group one have 56 patients with poor glycemic control (FPG >120 mg/dL, HbA1C > 7.5%) by OADs (sulfonylurea plus metformin) and were added with once-daily insulin glargine. With same condition, group two contains 67 patients were added with pioglitazone. After six months of data collection the mean of HbA1C (9.46 ± 1.67 vs 8.77 ± 1.73 ％, p<0.05) and FPG (168.97 ± 50.73 vs 138.35 ± 43.78 mg/dL, p<0.001) show a significantly decrease when compared to the baseline data in group one. Group two, however do not show any statistically significant changes of HbA1C and FPG after received six months of treatment. In weight changes, both two groups are significantly increased. TC, HDLC, TG, Scr and GPT levels in both groups are not change significantly, but LDL-C is significantly decreased in group two. Conclusions Adding once-daily insulin glargine is effective to decrease HbA1C and FPG in a six months period in type 2 diabetic patients who are inadequately controlled with sulfonylurea plus metformin. Except LDL-C, the results of safety profile are not statistically significant changes in both groups. Keyword Insulin glargine, Pioglitazone, Poor controlled of type 2 diabetes
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« Role of T-type calcium channels in basal [calcium(2+)](i) and insulin secretion in pancreatic beta-cells under hypergyclemia ». Tulane University, 2006.
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Hyperinsulinemia is a commonly associated with type II diabetes, this hyperinsulinemia often precedes the clinical diagnosis of type II diabetes by several years. It is believed that hyperinsulinemia is the mechanism by which the pancreatic beta-cell compensates for deteriorating peripheral insulin sensitivity. It has been shown that hyperinsulinemia accompanies an increase in the basal intracellular concentration of calcium ([Ca2+ ]i) in the pancreatic beta-cell. This increase in basal [Ca2+]i is detrimental to the pancreatic beta-cell. If these two events are links and the exact mechanism of both is currently not understood. In the present study we investigated if these two events are linked by the T-type Ca2+ channel. Since there are no available selective T-type Ca2+ channel antagonists, we set forth to develop both a compound and utilizing a new technique small interfering RNA (siRNA) to complete this study. We found that T-type Ca2+ channels were upregulated in hyperglycemia both at the mRNA and current level. Next, we discovered that the increase in basal [Ca2+]i was linked to T-type Ca2+ channels and that antagonizing them basal [Ca2+]i could be reduced to control levels. By taking advantage of a dual patch clamp/calcium imaging technique, T-type Ca2+ channel mediated window current was the mechanism in which T-type Ca2+ channels increased basal [Ca2+ ]i. Additionally we found that antagonism of T-type Ca2+ channels decreased basal insulin secretion. Taken together this data suggest that T-type Ca2+ channels play a role in both basal insulin release and basal [Ca2+]i in rat pancreatic beta-cells under conditions of hyperglycemiaacase@tulane.edu
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Pin-HaoChen et 陳品豪. « Comparative effectiveness of second-line initiation of basal insulin therapy versus oral antidiabetic drugs added to metformin therapy among Taiwanese patients with type 2 diabetes ». Thesis, 2018. http://ndltd.ncl.edu.tw/handle/nsfs75.
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Sousa, Moisés Simão Santa Rosa de. « Correlações entre os níveis sanguíneos de (glicose, leptina, insulina, LDL, HDL, colesterol total e triglicerídeos), compulsão alimentar, composição corporal, IMC, força muscular e taxa metabólica basal, antes e depois de um programa de 12 semanas de TR em diabéticos tipo II ». Doctoral thesis, 2014. http://hdl.handle.net/10348/3338.
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Tese de Doutoramento em Ciências do DesportoObjetivo: O objetivo deste estudo foi analisar as correlações existentes entre os níveis das variáveis sanguíneas (glicose, leptina, insulina, LDL, HDL, Colesterol Total e Triglicerídeos), compulsão alimentar, composição corporal, IMC, força muscular e TMB, em diabéticos tipo II, sedentários, submetidos a 12 semanas de treinamento resistido, bem como analisar o impacto do treinamento sobre estas variáveis. Método: A amostra foi composta aleatoriamente por 34 indivíduos adultos de ambos os sexos, portadores de diabetes tipo II e sedentários com idade média de 58.94 ± 10.66, peso corporal de 71.62 ± 11.85, IMC de 29.64 ± 4.27, percentual de gordura de 35.73 ± 7.42. Foram coletadas amostras laboratoriais de sangue para análise de leptina, glicose, Insulina, LDL, HDL, Colesterol Total e Triglicerídeos. A avaliação do IMC e composição corporal foi feita por meio da Bioimpedância elétrica. A compulsão alimentar foi verificada por meio do questionário da escala de compulsão alimentar periódica, e a força muscular através do teste de carga por repetições máximas. Os sujeitos foram submetidos a 12 semanas de treinamento resistido, com três sessões semanais em dias alternados, compostas por três séries de 12 a 15 repetições para os grandes grupos musculares. Resultado: Foram observadas redução significativas nos níveis de Leptina (LEP) (p <0.01*); aumento significativo no HDL (p <0.01*), reduções não significativas nas variáveis sanguíneas Glicose (GL); Colesterol Total (CT); Triglicerídeos (TG) e LDL, bem como um aumento não significativo da insulina (INS). Nas variáveis de composição corporal o treinamento proporcionou reduções significativas no peso corporal de (71,62 ± 11,85 kg para 69,61 ± 11,83 kg) (p < 0.01*); no % de gordura de (35.73 ± 7.42 para 33.62 ± 8.38) (p < 0.01*); no peso gordo de (25.59 ± 6.85 kg para 23.78 ± 7.00 kg) (p < 0.01*); no peso a perder de (12.19 ± 6.27 kg para 9.61 ± 6.17 kg) (p < 0.01*); e no IMC de (29.64 ± 4.27 para 28.80 ± 4.29) (p < 0.01*). Favoreceu também aumentos não significativos na massa corporal magra e na Taxa Metabólica Basal. Em relação à variável força muscular, constatou-se aumento significativo em todos os exercícios (p < 0,01*) bem como aumento no índice total de força de (87.89 ± 25.21 kg para 155.44 ± 31.46) sendo p < 0,01*. Antes do treinamento, com exceção da insulina, o nível de leptina se correlacionou com o IMC (p <0.01*); % de gordura (p <0.01*); peso gordo (p <0.01*) e compulsão alimentar (p <0.03*). Após o treinamento correlacionou-se com o IMC, Insulina, % de gordura, peso gordo e compulsão alimentar, sendo (p <0.01*) para todas as correlações, não sendo verificada correlação com a glicose. A compulsão alimentar correlacionou-se no pré treinamento com o IMC (p <0.01*); peso corporal (p <0.01*); colesterol total (p = 0.02*); LDL (p = 0.04*) e peso gordo (p = 0.01*), após o treinamento correlacionou-se apenas com o IMC (p <0.01*) e o peso corporal (p = <0.01*). Em relação à taxa metabólica basal, foram verificadas correlações com o IMC antes e após o treinamento (p = 0.04*) e (p = 0.05*) respectivamente; com o % de gordura, massa corporal magra (p = 0.01*) e (0.01*) e peso corporal total (p = 0.01*) e (0.01*) valores pré e pós respectivamente para cada um; com o índice total de força (p = 0.02*) e (p = 0.05*) no pré e pós respectivamente, e finalmente com a compulsão alimentar, antes e depois do treinamento, sendo os valores respectivos de (p = 0,03*) e (p = 0,05*). Conclusão: Com base nestes resultados, o treinamento resistido mostrou-se eficaz na melhoria da saúde do diabético tipo II. Mostrou-se ainda capaz de reduzir a leptinemia, sendo que esta redução foi acompanhada de modificações positivas na composição corporal, bem como nos sintomas da compulsão alimentar periódica, influenciando ainda com maior ou menor magnitude as variáveis, glicose, leptina, insulina, LDL, HDL, CT, Triglicerídeos, IMC, taxa metabólica, e força muscular em diabéticos tipo II.
Objective: The objective of this study was to analyze the correlation between levels of blood variables (glucose, leptin, insulin, LDL, HDL, Total Cholesterol, and Triglycerides), binge eating, body composition, BMI, muscle strength and BMR on diabetes type II, sedentary, undergo12 weeks of resistance training, as well analyze the impact of training on these variables. Method: The random sample consisted of 34 adults of both sexes, patients with type II diabetes and sedentary mean age of 58.94 ± 10.66, body weight 71.62 ± 11.85, BMI 29.64 ± 4.27, body fat percentage of 35.73 ± 7.42. Samples were collected for laboratory analysis of blood leptin, glucose, insulin, LDL, HDL, total cholesterol and triglycerides. The assessment of BMI and body composition was performed by electrical bioimpedance. Binge eating was assessed through the questionnaire the scale of binge eating, and muscle strength through the test load for maximum repetitions. The subjects underwent 12 weeks of resistance training, three sessions per week on alternate days, consisting of three sets of 12 to 15 repetitions for the major muscle groups. Results: We observed significant reduction in levels of leptin (LEP) (p <0.01 *) significant increase in HDL (p <0.01 *), no significant reductions in blood glucose variables (GL), total cholesterol (TC), triglycerides (TG) and LDL as well and nonsignificant increase in insulin (INS). Body composition variables in the training provided significant reductions in body weight (71.62 ± 11.85 kg to 69.61 ± 11.83 kg) (p <0.01 *) in % fat (35.73 ± 7:42 for 33.62 ± 8.38) (p <0.01 *) in the weight of fat (25.59 ± 6.85 kg to 23.78 kg ± 7:00) (p <0.01 *) to lose weight (12.19 ± 6.27 kg to 9.61 ± 6.17 kg) (p <0.01 *) and BMI (29.64 ± 4.27 to 28.80 ± 4.29) (p <0.01 *). Also favored non-significant increases in lean body mass and BMR. In relation to the variable strength, showed a significant increase in all exercises (p <0.01 *) and increased rate of total power (87.89 ± 25.21 to 155.44 ± 31.46 kg) and p <0.01 * . Before the training, with the exception of insulin, leptin levels correlated with BMI (p <0.01 *),% fat (p <0.01 *), fat weight (p <0.01 *) and binge eating (p <0.03 *). After training was correlated with BMI, insulin,% fat, fat weight and binge eating, being (p <0.01 *) for all correlations, no correlation was found with glucose. Binge eating was correlated with the pre-training BMI (p <0.01 *), weight (p <0.01 *), total cholesterol (p = 0.02 *), LDL (p = 0.04 *) and fat weight (p = 0:01 *), after training was correlated only with BMI (p <0.01 *) and body weight (p = <0.01 *). In relation to basal metabolic rate, correlations were observed with BMI before and after training (p = 0.04 *) and (p = 0.05 *) respectively, with % of fat, lean body mass (p = 0.01 *) and ( * 12:01) and total body weight (p = 0.01 *) and (0.01 *) values pre and post respectively for each one, with the overall level of strength (p = 0.02 *) and (p = 0.05 *) before and after respectively, and finally with binge eating, before and after training, with the respective values of (p = 0.03 *) and (p = 0.05 *). Conclusion: Based on these results, resistance training was effective in improving the health of Type II diabetes. Was even able to reduce leptin levels, and this reduction was accompanied by positive changes in body composition as well as the symptoms of binge eating, influencing even with greater or lesser magnitude variables, glucose, leptin, insulin, LDL, HDL, TC, triglycerides, BMI, metabolic rate, and muscle strength in type II diabetics.
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Berndt-Zipfel, Christine. « Nächtliche Glucoseanstiege durch die Stressreaktion beim Klingeln eines Weckers können durch geschultes Pflegepersonal vermieden werden. Eine Analyse mittels kontinuierlichen Glucose-Monitorings (GlucoDay® S) bei Patienten mit Typ-1-Diabetes ». Doctoral thesis, 2011. http://hdl.handle.net/11858/00-1735-0000-0006-B21D-9.
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