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Inicio Endocrinología y Nutrición Nuevos abordajes terapéuticos de la diabetes mellitus tipo 1
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Vol. 51. Núm. 5.
Páginas 277-286 (Mayo 2004)
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Vol. 51. Núm. 5.
Páginas 277-286 (Mayo 2004)
DOI: 10.1016/S1575-0922(04)74617-3
Acceso a texto completo
Nuevos abordajes terapéuticos de la diabetes mellitus tipo 1
New therapeutic approaches in type 1 diabetes mellitus
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D. Acosta
Autor para correspondencia
domingo.acosta.sspa@juntadeandalucia.es
dacostade@sarenet.es

Correspondencia: Dr. D. Acosta. Servicio de Endocrinología y Nutrición. Centro de Diagnóstico y Tratamiento. Hospitales Universitarios Virgen del Rocío. Avda. Manuel Siurot, s/n. 41013 Sevilla. España.
Servicio de Endocrinología y Nutrición. Hospitales Universitarios Virgen del Rocío. Sevilla. España
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La necesidad de conseguir un adecuado tratamiento sustitutivo en la diabetes mellitus tipo 1 ha ido dirigida a obtener una adecuada imitación de la secreción endógena de insulina y su comportamiento fisiológico ante los picos de hiperglucemia. Esto ha planteado 2 grandes retos: la obtención de nuevas insulinas y el desarrollo de nuevas formas de administración de la insulina. En relación con las nuevas insulinas, los primeros resultados se obtuvieron con la consecución de análogos de insulina de acción rápida (lispro y aspart). Sin embargo, en las pautas intensivas a través de multidosis de insulina también se necesita usar insulinas de acción retardada, por lo que es preciso mejorar las características de las insulinas retardadas con cinc y las insulinas isófanas, debido a la falta de reproducibilidad farmacocinética, la presencia de “picos” de absorción y la alta variabilidad de absorción intrasujeto. Todo ello dio lugar a la necesidad de obtener análogos de insulina de acción prolongada, cuyo comportamiento fuera más uniforme. Así, en la actualidad contamos con las insulinas glargina y detemir. El perfil de acción de la insulina glargina viene determinado por la microcristalización a pH fisiológico en el tejido celular subcutáneo, y el perfil de acción de la insulina detemir viene determinado por la unión de la molécula de ácido mirístico a los receptores de ácidos grasos de la albúmina, tanto instersticial como plasmática.

El desarrollo de las nuevas formas de administración de insulina se ha basado fundamentalmente hasta la fecha en el uso de sistemas de infusión continua de insulina, cuyas ventajas teóricas se basan en 2 principios básicos: sólo se usa insulina rápida, la cual se administra en infusión continua y en bolos, y la infusión es además programable. Además, debe tenerse en cuenta que la ausencia de autonomía de dichos sistemas requiere una importante implicación del paciente en su tratamiento.

Existen otras vías alternativas de administración de insulina (jetinyectores, transdérmica, intranasal, oral entérica, oral bucal, pulmonar), si bien la pulmonar es la más desarrollada.

Por último, los sistemas implantables de asa cerrada con sensores de glucosa pueden ser una opción terapéutica muy adecuada para el tratamiento del paciente con diabetes mellitus tipo 1.

Palabras clave:
Análogos de insulina de acción prolongada
Insulina glargina
Insulina detemir
Sistemas de infusión continua de insulina

The need for an ideal substitute therapy in type 1 diabetes mellitus has been directed to imitate the endogenous insulin secretion and its physiological response with peaks of hyperglycaemia. This has raised 2 great challenges: discovery new forms of insulins and new forms of insulin administration. In relation to new form of insulins, the development of short acting insulin analogs (lispro and aspart) was a great achievement, but intensive therapy by multidose of insulin also needed the use of long-acting insulins. This created the need to improve the longacting Zn-insulin and NPH-insulin, which lacked pharmacokinetic reproducibility, great variability of absorption, including the presence of absorption peaks. Presently, long acting insulin analogs with a more uniform pharmacological behaviour had been achieved with glargine and detemir insulins. The mode of action of glargine insulin is determined by its microcrystalization in a physiological pH in the subcutaneous cellular tissue, and the mode of action of determir insulin is determined by the union of the myristic acid molecule with both interstitial and plasmatic albumin-fatty acid receptors. On the other hand, to date, the new forms of insulin administration has been based fundamentally on the use of continuous subcutaneous insulin infusion, whose theoretical advantages are based on 2 basic principles: the only use of rapid insulin by continuous infusion and bolus administration, and, in addition, the insulin infusion is programmable. Its lack of autonomy requires an important implication on the part of the patient. Other alternative routes of insulin administration are jet-injectors, transdermal, oral enteric, oral buccal, intranasal, and pulmonary delivery. To date, pulmonary administration is the most developed. Finally, implantable systems of closed-loop with glucose sensors can constitute a very suitable therapeutic alternative in the treatment of type 1 diabetic patients.

Key words:
Long-acting insulin analogs
Glargine insulin
Detemir insulin
Continuous subcutaneous insulin infusion
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