De la bomba de insulina y el monitoreo continuo de glucosa al páncreas artificial / From insulin pump and continuous glucose monitoring to the artificial pancreas

Technology for diabetes care has undergone major development during recent decades. These technological advances include continuous subcutaneous insulin infusion (CSII), also known as insulin pumps, and real-time continuous glucose monitoring system (RT-CGMS). The integration of CSII and RT-CGMS into a single device has led to sensor-augmented pump therapy and more recently, a technology that has automated delivery of basal insulin therapy, known as hybrid system. These new technologies have led to benefits in attaining better metabolic control and decreasing the incidence of severe hypoglycemia, especially in patients with type 1 diabetes. This review describes the types of technologies currently available or under investigation for these purposes, their benefits and disadvantages, recommendations and the appropriate patient selection for their use. The clinical use of the hybrid system and artificial pancreas seem to be possible in the near future.

Artificial Pancreas: A Concise Review / 임상당뇨병

Artificial pancreas is a technique developed to automatically control blood glucose in people with diabetes by providing an endocrine function instead of a healthy pancreas. The technique was developed for the replacement of insulin secretion deficiencies among various exocrine and endocrine functions of the pancreas and is mainly used for people with type 1 diabetes or those who need intensive insulin treatment. This review briefly summarizes the working principles, components, recent clinical research, and future perspectives of artificial pancreas.

New Technology for Type 1 Diabetes / 임상당뇨병

Type 1 diabetes is an autoimmune disease with insulin deficiency which causes microvascular complications such as retinopathy, nephropathy and neuropathy. There have been some trials to simulate the pancreatic endocrine function of insulin and glucagon for homeostatic equilibration of blood glucose, developing artificial pancreas. There are three major functional components of the modern artificial pancreas, a continuous glucose-monitoring system, an insulin-infusion pump and a control algorithm. There are commercially available continuous glucose monitoring systems with subcutaneous glucose measuring, however, there have been many attempts to develop more efficient glucose monitoring systems, including noninvasive systems. Thanks to technological advances and the miniaturization of electronics, recent advances in the accuracy and performance of these systems have placed research on the threshold of prototype commercial devices and large-scale outpatient feasibility studies. In addition, smartphone technology has created the opportunity for caregivers to receive push notification alerts and makes it possible to provide patients with advisory or decision-support systems. Even though there are still some remaining challenges to develop a successful artificial pancreas, glucose control in type 1 diabetes will be more efficient with its advent.

Clinical experience with an implanted closed-loop insulin delivery system

AIM: To report the first clinical experience with a prototype of implanted artificial beta-cell. METHODS: The Long-Term Sensor System® project assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor, connected physically by a subcutaneous lead and functionally by PID algorithms. It was performed in 10 type 1 diabetic patients from 2000 to 2007. RESULTS: No harmful complication related to implants occurred. Insulin delivery was affected by iterative but reversible pump slowdowns due to insulin precipitation. Glucose measurement by the intravenous sensors correlated well with meter values (r = 0.83-0.93, with a mean absolute deviation of 16.5 percent) for an average duration of 9 months. Uploading of pump electronics by PID algorithms designed for closed-loop insulin delivery allowed in-patient 48 hourtrials. CONCLUSION: Although the concept of a fully implantable artificial beta-cell has been shown as feasible, improvements in the sensor structure to increase its longevity and decrease sensor delay that affected closed-loop control at meal-times are expected.

OBJETIVO: Relatar a primeira experiência clínica com um protótipo de célulabeta artificial implantável. MÉTODOS: O Projeto de Um Sistema Sensor de Longo Prazo avaliou a possibilidade do controle glicêmico através do implante combinado de uma bomba de infusão de insulina peritoneal e um gluco - sensor endovenoso central - conectados fisicamente por um dispositivo subcutâneo e funcionalmente por algoritmos PID (integral and derivative). Este projeto envolveu 10 pacientes com diabetes melito tipo 1 de 2000 a 2007. RESULTADOS: Complicações significativas relacionadas aos implantes não ocorreram. A liberação de insulina pela bomba sofreu o efeito de períodos de lentificação interativo, mas reversível, devido a precipitação do peptídeo. As medidas da glicose pelo sensor endovenoso mostraram boa correlação com os valores do glicosímetro (r = 0,83-0,93, com desvio médio absoluto de 16,5 por cento) durante período médio de 9 meses. Os dados para construção dos algoritmos PID do sistema de alça fechada de liberação de insulina foram obtidos a partir de 12 pacientes que permaneceram internados com esse sistema durante 48 horas com refeições que continham 40 a 70 g de carboidratos. CONCLUSÃO : Embora o conceito de uma célula-beta artificial totalmente implantável tenha demonstrado ser possível, aperfeiçoamentos são necessários na estrutura do sensor para aumentar a sua longevidade e no sistema de alça fechada de liberação de insulina para diminuir as lentificações que comprometem o controle glicêmico nos períodos relacionados às refeições.

Caged Pancreatic Islet for IDDM

The goals of this research are to improve the functionality (insulin secretion rate and pattern) and to expand the life-span of immunoprotected pancreatic islets. The low functionality (less than 15% of the insulin release rate of native islets in pancreas) required a large number of islets within the implant, which causes complications in surgery and discomfort for patients. The limited life-span of the islets in a biohybrid artificial pancreas (BAP) may require frequent cell reseeding and cause further supply problems in islet transplantation. Improved islet functionality and prolonged life-span will minimize the volume of the BAP by reducing the number of islets needed for diabetic patients to achieve normoglycaemia and reduce problems associated with islet supply. It is hypothesized in this research that 1) by mimicking facilitated oxygen transport in avascular tissues, the immunoprotected islets release a higher amount of insulin, recover their intrinsic biphasic release pattern, and prolong their life-span, and 2) insulinotropic agents further promote insulin secretion from islets. Based on these hypotheses, a new BAP system will be designed which contains the water-soluble polymeric conjugates of oxygen carriers (or oxygen binding vehicles) and islet stimulants of sulfonylurea compounds and glucagon-like insulinotropic peptide-1 with entrapped islets in the BAP. The research examines their effects on islet viability, the amount of insulin secretion, the insulin release profile, and the life-span of immunoprotected pancreatic islets. Especially, the combined synergy effects of both hypotheses will be emphasized. The successful results in improving functionality and life- span of islets entrapped in an immunoprotected membrane can be applied in the delivery of microencapsulated therapeutic cells and to the miniaturization of a BAP. In addition, the approaches proposed in this research will provide a potential solution to the shortage problem of human cell or tissue sources.

Reversión de la diabetes en el ratón por el xenotrasplante de islotes porcinos en un páncreas bioartificial / Reversion of diabetes type I in the mice with diffusion chambers of pig islets an bioartificial pancreas model

Antecedentes: El páncreas bioartificial permitiría la utilización de islotes porcinos para la reversión de la diabetes tipo I en humanos. Distintos modelos se han creado hasta el presente, presentando diversos problemas, que limitan su aplicación clínica. Objetivo: Evaluar el modelo de páncreas bioartificial, con cámaras de difusión en un xenotrasplante discordante (cerdo-ratón). Material y Métodos: Ratones hembras diabéticos por Streptozotocin, fueron utilizados como receptores de islotes porcinos. Se introdujeron en agarosa, 2000 islotes en cada cámara, formadas con arandelas de acrílico adheridas a 2 membranas semipermeables de policarbonato. El diseño experimental: Grupo 1 (n = 4): 4000 islotes porcinos no encapsulados en cápsula renal. Grupo 2 (n = 4): 1 cámara c/u en el abdomen. Grupo 3 (n = 6): 2 cámaras c/u. Grupo 4 (n = 2): 3 cámaras c/u. Se evaluó en cada grupo las variaciones de glucemia y la reacción histológica pericámara. Resultados: En el grupo 1, la reversión de la diabetes no superó los 3 días. De los 12 ratones con cámaras de difusión, el 50 por ciento alcanzó la normoglucemia, manteniéndose en el 33,3 por ciento hasta la 5ta. semana fecha en la que se sacrificaron. Ninguno de los ratones con una cámara normaliza la glucemia, como en el 100 por ciento de los que poseían tres. Importante reacción inflamatoria pericámara, se halla en la 1era. y 5ta. semana. Conclusiones: Resultados auspiciosos; necesidad de ampliar la experiencia utilizando 6000 o más islotes por ratón, y un mayor número de estos para encontrar nuevas estrategias que disminuyan la inflamación pericámara, mejorando a largo plazo la supervivencia del injerto

Caracterisiticas funcionales de los islotes de Langerhans en el pancreas heterotopico gastrico tipo I / Functional characteristics of the Langerhans's islets of the type I gastric heterotopic pancreas

Se realiza una búsqueda retrospectiva de tumoraciones parietales gástricas durante un periodo de 5 años. Se seleccionan las que corresponden a páncreas heterotópico con ambos componentes, exócrino y endócrino (páncreas heterotópico tipo I). Se valora el grado de fibrosis e infiltrado inflamatorio del tejido oberrante, así como tambien el patrón de producción hormonal mediante detección inmuhistoquímica para insulina, glucagón, sustancia P, somastotatina, gastrina y antiquimiotripsina. Nínguno de los casos mostró fíbrosis marcada ni infiltrado inflamatorio. Desde el punto de vista inmunohistoquímico encontramos que los islotes varían desde los monosecretantes a polisecretantes (2 o 3 hormonas o péptidos) para hormonas secretadas por el páncreas normal. Documentamos la negatividad para gastrina y antiquimiotripsina.