Bienvenidos a un encuentro con la diabetes tipo 1

"El objeto de este sitio es publicar novedades cientificas, relacionadas con prevencion, diagnostico, complicaciones, tratamiento de diabetes tipo 1, como asi tambien comunicar futuros eventos (congresos, jornadas, campamentos educativos, etc) en el pais e internacionales.
Dirigido a equipo de salud de atencion diabetologica (medicos, enfermeros, educadores, nutricionistas, asistentes sociales, profesores de educacion fisica, psicologos, podologos, etc.), empresas de medicina, pacientes y sus familiares."

miércoles, 28 de junio de 2017

DR.BERCOVICH: GENETICA Y DIABETES


DEFECTO GENETICO COMUN EN CELUAS BETA DE PACIENTES TIPO 1 y 2 ?

New study may lead to improved treatment of type 2 diabetes


Genetic cause found for loss of beta cells during diabetes development

Worldwide, 400 million people live with diabetes, with rapid increases projected. Patients with diabetes mostly fall into one of two categories, type 1 diabetics, triggered by autoimmunity at a young age, and type 2 diabetics, caused by metabolic dysfunction of the liver. Despite being labeled a “lifestyle disease”, diabetes has a strong genetic basis. New research under the direction of Adrian Liston (VIB/KU Leuven) has discovered that a common genetic defect in beta cells may underlie both forms of diabetes. This research was published in the international scientific journal Nature Genetics.

Adrian Liston (VIB/University of Leuven): “Our research finds that genetics is critical for the survival of beta cells in the pancreas – the cells that make insulin. Thanks to our genetic make-up, some of us have beta cells that are tough and robust, while others have beta cells that are fragile and can’t handle stress. It is these people who develop diabetes, either type 1 or type 2, while others with tougher beta cells will remain healthy even in if they suffer from autoimmunity or metabolic dysfunction of the liver.”
 

Different pathways to diabetes development
Diabetes is a hidden killer. One out of every 11 adults is suffering from the disease, yet half of them have not even been diagnosed. Diabetes is caused by the inability of the body to lower blood glucose, a process normally driven by insulin. In patients with type 1 diabetes (T1D), this is caused by the immune system killing off the beta cells that produce insulin. In patients with type 2 diabetes (T2D), a metabolic dysfunction prevents insulin from working on the liver. In both cases, left untreated, the extra glucose in the blood can cause blindness, cardiovascular disease, diabetic nephropathy, diabetic neuropathy and death.

In this study, an international team of researchers investigated how genetic variation controls the development of diabetes. While most previous work has focused on the effect of genetics in altering the immune system (in T1D) and metabolic dysfunction of the liver (in T2D), this research found that genetics also affected the beta cells that produce insulin. Mice with fragile beta cells that were poor at repairing DNA damage would rapidly develop diabetes when those beta cells were challenged by cellular stress. Other mice, with robust beta cells that were good at repairing DNA damage, were able to stay non-diabetic for life, even when those islets were placed under severe cellular stress. The same pathways for beta cell survival and DNA damage repair were also found to be altered in diabetic patient samples, indicating that a genetic predisposition for fragile beta cells may underlie who develops diabetes. 
 

Adrian Liston (VIB/University of Leuven): “While genetics are really the most important factor for developing diabetes, our food environment can also play a deciding role. Even mice with genetically superior beta cells ended up as diabetic when we increased the fat in their diet.”

A new model for testing type 2 diabetes treatments
Current treatments for T2D rely on improving the metabolic response of the liver to insulin. These antidiabetic drugs, in conjunction with lifestyle interventions, can control the early stages of T2D by allowing insulin to function on the liver again. However during the late stages of T2D, the death of beta cells means that there is no longer any insulin being produced in the pancreas. At this stage, antidiabetic drugs and lifestyle interventions have poor efficacy, and medical complications arise.

Dr Lydia Makaroff (International Diabetes Federation, not an author of the current study): “The health cost for diabetes currently exceeds US$600 billion, 12% of the global health budget, and will only increase as diabetes becomes more common. Much of this health care burden is caused by late-stage type 2 diabetes, where we do not have effective treatments, so we desperately need new research into novel therapeutic approaches. This discovery dramatically improves our understanding of type 2 diabetes, which will enable the design of better strategies and medications for diabetes in the future”.
 

Adrian Liston (VIB/University of Leuven): “The big problem in developing drugs for late-stage T2D is that, until now, there has not been an animal model for the beta cell death stage. Previously, animal models were all based on the early stage of metabolic dysfunction in the liver, which has allowed the development of good drugs for treating early-stage T2D. This new mouse model will allow us, for the first time, to test new antidiabetic drugs that focus on preserving beta cells. There are many promising drugs under development at life sciences companies that have just been waiting for a usable animal model. Who knows, there may even be useful compounds hidden away in alternative or traditional medicines that could be found through a good testing program. If a drug is found that stops late-stage diabetes, it would really be a major medical breakthrough!”


Publication:

Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetesDooley J* Tian L* Schönefeldt S* Delghingaro-Augusto V* Garcia-Perez J Pasciuto E Di Marino D Carr E Oskolkov N Lyssenko V Franckaert D Lagou V Overbergh L Vandenbussche J Allemeersch J Chabot-Roy G Dahlstrom J Laybutt D Petrovsky N Socha L Gevaert K Jetten A Lambrechts D Linterman M Goodnow C Nolan C Lesage S Schlenner S* Liston A*NATURE GENETICS, 48, 519-27, 2016

DR. BERCOVICH: INSULINA TRESIBA

INSULINA TRESIBA




Resumen del EPAR para el público general Tresiba insulina Degludec.




 El presente documento resume el Informe Público Europeo de Evaluación (EPAR) de Tresiba. En él se explica cómo el Comité de Medicamentos de Uso Humano (CHMP) ha evaluado dicho medicamento y emitido un dictamen favorable para su autorización de comercialización y unas recomendaciones sobre las condiciones de su uso.

Tresiba es un medicamento que contiene el principio activo insulina degludec. Se presenta en solución inyectable en un cartucho (100 unidades/ml) y en pluma precargada (100 unidades/ml y 200 unidades/ml). ¿Para qué se utiliza Tresiba? Tresiba se utiliza para tratar la diabetes de tipo 1 y de tipo 2 en adultos y en niños de entre 1 y 18 años. Este medicamento solo se podrá dispensar con receta médica.

  Tresiba debe inyectarse una vez al día, preferentemente a la misma hora cada día. Tresiba se administra por vía subcutánea mediante inyección en el muslo, la zona superior del brazo o la pared abdominal (sobre la parte delantera de la cintura). Siempre se debe cambiar el punto de inyección dentro de una misma zona para reducir el riesgo de lipodistrofia (alteraciones en la distribución de la grasa corporal) debajo de la piel, lo cual puede afectar a la cantidad de insulina que se absorbe. La dosis correcta se determina de forma individual para cada paciente. En la diabetes de tipo 1, Tresiba siempre se debe utilizar en combinación con una insulina de acción rápida que se inyecta durante las comidas. En la diabetes tipo 2, Tresiba se puede administrar en monoterapia o en combinación con otros hipoglucemiantes orales.

  La diabetes es una enfermedad en la que el organismo no produce insulina suficiente para controlar las concentraciones de glucosa en sangre o es incapaz de utilizar la insulina de manera eficaz. Tresiba es un sustituto de la insulina que se asemeja mucho a la insulina natural con la diferencia de que es absorbida más lentamente en el organismo y necesita más tiempo para alcanzar su objetivo. Esto significa que Tresiba tiene un periodo de actuación largo. Tresiba actúa de la misma forma que la insulina producida naturalmente y contribuye a que la glucosa pase de la sangre al interior de las células. Controlar la concentración de glucosa en sangre permite reducir los síntomas y complicaciones de la diabetes.

 Estudios realizados con Tresiba:

 Tresiba se ha estudiado en tres estudios principales en los que participaron 1 578 adultos con diabetes de tipo 1 en los que se comparó Tresiba (en combinación con una insulina de acción rápida en las comidas) con la insulina glargina o la insulina detemir (otras insulinas de acción prolongada). En otros seis estudios principales en los que participaron 4 076 adultos con diabetes de tipo 2 se comparó Tresiba con la insulina glargina, la insulina detemir o la sitagliptina (un medicamento que se toma por vía oral para la diabetes tipo 2). En caso necesario, también se podría administrar a los pacientes otros medicamentos para la diabetes o insulina de acción rápida durante las comidas. Otro estudio principal en el que participaron 177 adultos con diabetes de tipo 2 investigó la eficacia de combinar Tresiba y liraglutida (un agonista del receptor GLP-1). Tresiba también se comparó con la insulina detemir en un estudio principal en el que participaron 350 niños de entre 1 y 18 años con diabetes tipo 1. A los pacientes se les administró igualmente insulina de acción rápida durante las comidas. Tras 26 semanas de tratamiento, los pacientes podían bien interrumpir el tratamiento o bien continuarlo durante un periodo máximo de un año. Todos los estudios midieron las concentraciones en sangre de una sustancia denominada hemoglobina glicosilada (HbA1c), que es el porcentaje de hemoglobina en sangre unida a la glucosa. La HbA1c proporciona una indicación de hasta qué punto se controla bien la glucemia. Los estudios duraron seis meses o un año. ¿Qué beneficios ha demostrado tener Tresiba durante los estudios? Los estudios han demostrado que Tresiba era como mínimo tan eficaz como las demás insulinas de acción prolongada para el control de la glucemia en adultos con diabetes de tipo 1 y tipo 2 y más eficaz que la sitagliptina en adultos con diabetes de tipo 2. En todos los estudios la reducción media de los niveles de HbA1c con Tresiba fue del 0,6 % en adultos con diabetes de tipo 1 y del 1,2 % en adultos con diabetes de tipo 2. En los niños, los efectos de Tresiba en el control de la glucemia fueron similares a los de la insulina detemir. Tras 26 semanas de tratamiento con Tresiba, la reducción media de los niveles de HbA1c fue del 0,2 % (la HbA1c pasó del 8,2 % al 8,0 %) en comparación con la reducción del 0,3 % en el caso de la insulina detemir (la HbA1c pasó del 8,0 % al 7,7 %). Tresiba EMA/27727/2015 Página 2/3
  El efecto adverso más frecuente de Tresiba (observado en más de un paciente de cada 10) es la hipoglucemia (concentraciones bajas de glucosa en sangre). Para consultar la lista completa de efectos adversos y restricciones de Tresiba, ver el prospecto. ¿Por qué se ha aprobado Tresiba? El CHMP concluyó que Tresiba es eficaz en el control de las concentraciones de glucosa en sangre en pacientes con diabetes de tipo 1 y de tipo 2. Con respecto a su seguridad, el Comité concluyó que Tresiba es, en general, seguro y que sus efectos adversos son comparables a los observados en otros análogos de la insulina, sin que se hayan notificado efectos adversos inesperados. También cabe destacar que Tresiba reduce el riesgo de hipoglucemia nocturna en pacientes con diabetes de tipo 1 y de tipo 2. El CHMP indicó que la formulación de mayor concentración de Tresiba satisfacía una necesidad médica en pacientes que requieren mayores dosis de insulina (como los pacientes con sobrepeso), lo que permitiría a estos pacientes tomar la dosis diaria en una única inyección en vez de en dos. Para los adolescentes con diabetes de tipo 2, el CHMP concluyó que aunque la seguridad y la eficacia solo se habían mostrado para la diabetes de tipo 1, los resultados de los estudios en adolescentes con tipo 1 y otros estudios en adultos con tipo 2 podrían aplicarse a los adolescentes con diabetes de tipo 2. El CHMP decidió que los beneficios de Tresiba son mayores que sus riesgos y recomendó autorizar su comercialización.

 Se ha elaborado un plan de gestión de riesgos para garantizar que Tresiba se administra de una forma lo más segura posible. Basándose en este plan, se ha incluido en el Resumen de las características del Producto y el prospecto de Tresiba la información sobre seguridad que incluye las precauciones pertinentes que deben tomar los profesionales sanitarios y los pacientes. La empresa que comercializa Tresiba proporcionará material educativo a los profesionales sanitarios responsables de tratar o dispensar medicamentos a los diabéticos, destinado en concreto a aumentar la información sobre la formulación de la nueva concentración de Tresiba para garantizar que se ha recetado al paciente la dosis correcta. También aportará a los pacientes material de formación con instrucciones sobre el uso correcto de Tresiba, que deberá ser entregado por el médico, además de recibir una formación adecuada. Otras informaciones sobre Tresiba La Comisión Europea emitió una autorización de comercialización válida en toda la Unión Europea para Tresiba el 21 de enero de 2013. El EPAR completo de Tresiba se puede consultar en la página web de la Agencia: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. Para mayor información sobre el tratamiento con Tresiba, lea el prospecto (también incluido en el EPAR) o consulte a su médico o farmacéutico. Fecha de la última actualización del presente resumen: 01-2015. Tresiba EMA/27727/2015 P



European Medicines Agency

DR. BERCOVICH: INSULINAS BIOSIMILARES

INSULINAS BIOSIMILARES


INICIO DE PRESCRIPCIONES CON INSULINA ABASAGLAR®




BIOSIMILAR: Según la Agencia Europea de Medicamentos (EMA) un medicamento biosimilar es un medicamento biológico que se desarrolla para que sea similar a un medicamento biológico ya existente (el «medicamento de referencia»). Los biosimilares no son iguales a los genéricos, que tienen estructuras químicas más simples y se consideran idénticos a sus medicamentos de referencia . El principio activo de un biosimilar y su medicamento de referencia es esencialmente la misma sustancia biológica, aunque existen ligeras diferencias debido a la complejidad de su naturaleza y a los métodos de producción. Al igual que el medicamento de referencia, el biosimilar posee un grado de variabilidad natural. La EMA aplica unos criterios estrictos en la evaluación de los estudios que comparan la calidad, la seguridad y la eficacia de estos medicamentos. Cuando se autoriza, se demuestra que la variabilidad y las diferencias entre él y su medicamento de referencia no afectan a la seguridad ni a la eficacia . En general, un medicamento biosimilar se utiliza en la misma dosis para tratar la misma enfermedad. Si existieran precauciones específicas que deban considerarse a la hora de tomar el medicamento de referencia, en general también serán aplicables al biosimilar . El Departamento de Salud del Gobierno Vasco,  impulsan la utilización de biosimilares ya que mejora la eficiencia y ayuda a contener el gasto sanitario. Los medicamentos biosimilares (medicamentos similares en calidad, seguridad y eficacia a los productos de referencia) son una alternativa equivalente y más económica, lo que no sólo contribuye a la sostenibilidad del sistema sanitario público, sino que supone un mejor acceso de los pacientes a las terapias biológicas. Esto significa que se podrá tratar a un mayor número de pacientes con el presupuesto disponible o, si así se decide, se podrán destinar recursos liberados a la financiación de otros tratamientos. Recientemente se ha comercializado un medicamento biosimilar de la insulina glargina (ABASAGLAR® 100 U/ML solución inyectable 5 pluma precargadas de 3 ml) para el tratamiento de la diabetes mellitus en adultos, adolescentes y niños a partir de dos años de edad .Usar  ABASAGLAR®en lugar de insulina LANTUS, supone un ahorro estimado anual por paciente para el sistema sanitario de 96€. Si todos los nuevos pacientes iniciaran el tratamiento con el biosimilar ABASAGLAR®, se estima un ahorro durante el primer año de 156.000€. Debido al ahorro que supondría la sustitución de la insulina glargina LANTUS® por su biosimilar sin afectar a la eficacia ni a la seguridad de los tratamientos, se recomienda utilizar el biosimilar ABASAGLAR®en todos los pacientes que inicien tratamiento con insulina glargina.

BIBLIOGRAFIA:

 1. European Medicines Agency. Preguntas y respuestas sobre medicamentos biosimilares (medicamentos biológicos similares). 27 de septiembre de 2012. EMA/837805/2011. Disponible en:http://www.ema.europa.eu/docs/es_ES/document_library/Medicine_QA/2009/12/WC500020 062.pdf

 2. European Medicines Agency:  Ficha técnica de ABASAGLAR. http://www.ema.europa.eu



miércoles, 21 de junio de 2017

DR.BERCOVICH: DIABETES Y SUEÑO


SUEÑO Y DIABETES








¿TIENEN UN MAYOR RIESGO DE DIABETES LAS PERSONAS CON TRASTORNOS DEL SUEÑO?

 En los últimos años diferentes estudios han evaluado si las personas con trastorno del sueño tienen más riesgo de desarrollar enfermedades metabólicas. En muchos de ellos el acortamiento de los periodos de sueño se asocia con un mayor riesgo de obesidad y de DM tipo 2. En el Estudio Pizarra un estudio de cohortes llevado a cabo en el Sur de España (Pizarra: Málaga), la incidencia (casos nuevos) de obesidad a los 11 años de seguimiento fue mayor en aquellas personas que dormían menos horas . Igual ocurría con la incidencia de DM tipo 2, aunque esta mayor incidencia no era totalmente independiente de la incidencia de obesidad ni de la existencia de una “prediabetes” previa.


 ¿SON LOS TRASTORNOS DEL SUEÑO MÁS FRECUENTES EN LA DIABETES?

 Los estudios sobre prevalencia de trastornos del sueño son difíciles de comparar entre sí pues los criterios seguidos para definirlos no son homogéneos. En un estudio realizado por Maurice M. Ohayon y Teresa Sagales sobre 4065 personas mayores de 15 años, encontraron que el insomnio es frecuente en España afectando a uno de cada cinco personas . En el año 2008 finalizó el trabajo de campo del Estudio Di@betes . En este estudio, además de la prevalencia de diabetes se investigaron numerosos factores sociológicos y ambientales, entre ellos el número de horas de sueño de la población, incluida la población de personas con diabetes y “prediabetes”. La población española duerme una media de 7,33±1,24 horas. La distribución de las horas de sueño siguen la forma de una U invertida en función de la edad . Los resultados del estudio muestran que el patrón de sueño poblacional está condicionado por numerosos factores, entre ellos factores biológicos como la edad y el sexo; geográficos como el lugar donde se vive; socioeconómicos como el nivel de estudio, situación laboral o marital; hábitos de salud, como el tabaco o la toma de café o infusiones; farmacológicos (toma de psicótropicos, anti psicóticos, y antidepresivos); o la calidad de vida (todos ellos relacionados, especialmente, en el número de horas extremas de sueño(<=6- horas y >8 horas). El sueño es una función biológica, como cualquier otra, a la que dedicamos cerca de un tercio de nuestra vida y sobre el que aun sabemos muy poco. Dormir es una función vital, de similar importancia a la alimentación pues sin dormir se puede sobrevivir aproximadamente el mismo tiempo que sin comer, habiéndose descrito numerosos problemas de salud relacionados con los trastornos del sueño y entre los más frecuentes esta el insomnio, el síndrome de piernas inquietas, ronquido, excesiva somnolencia y apnea del sueño. En este artículo intentaremos contestar a las siguientes cuestiones:  Después de ajustar por diferentes variables, el OR (Odds Ratio) de llegar a ser obeso fue significativamente mayor en aquellos sujetos que habían dormido ≤7 por noche, tanto a los 6 años de seguimiento (OR=1.99; 95% CI=1.12-3.55), como a los 11 años (OR=2.73; 95% CI=1.47-5.04). La incidencia de Diabetes Mellitus tipo 2 a los 6 años de seguimiento en las personas sin diabetes al comienzo del estudio fue mayor en aquellos que durmieron ≤7 por noche (OR=1.96; 95% CI=1.10-3.50), sin embargo esta asociación no fue independiente de la presencia de obesidad, de la ganancia de peso en el periodo de tiempo en el seguimiento ni de la existencia de una “prediabetes” al comienzo del estudio. Por otro lado a los 11 años de seguimiento no hubo una asociación entre el número de horas dormido y la incidencia de Diabetes Mellitus tipo 2 . En este texto se considera “prediabetes” aquellas personas con una glucemia basal alterada (GBA), tolerancia anormal de la glucosa (TAG) o ambas.
 DORMIR ES UNA FUNCIÓN VITAL, DE SIMILAR IMPORTANCIA A LA ALIMENTACIÓN PUES SIN DORMIR SE PUEDE SOBREVIVIR APROXIMADAMENTE EL MISMO TIEMPO QUE SIN COMER En el Estudio Di@bet.es, el número de horas de sueño nocturno ha sido significativamente mayor en las personas con algún trastorno del metabolismo de los CHO (p=0,0002). Esta diferencia ha sido independiente de la edad y sobre todo a expensas del mayor número de horas de sueño en las mujeres con diabetes. Las mujeres con DM2 (Diabetes Mellitus tipo 2 han dormido con más frecuencia >8 horas (OR=1,73; IC95% 1,25-2,39, p=0,001; después de ajustar por la edad, nivel de estudios y toma de psicotropicos. Por el contrario la probabilidad de dormir <=6,5 horas/día ha sido similar en mujeres con o sin diabetes. En hombres, en ningún caso, hubo asociación significativa entre el número de horas dormidas y la presencia de DM2. Por otro lado, desde una perspectiva poblacional, la curva de distribución de las horas de sueño en función de la edad, ha sido similar a la de la población con una sobrecarga oral de glucosa normal, tanto en las personas con diabetes conocida, como desconocida, como con cualquiera de los trastornos “prediabéticos“. Estos resultados del estudio español no son concordantes con los de muchos de los publicados en los últimos años. La mayoría de ellos llegan a la conclusión de que la prevalencia de trastornos relacionados con el sueño son más frecuentes en las personas con diabetes. Por lo general los trastornos del sueño en las personas con diabetes son secundarios a algunas de las complicaciones asociadas a la diabetes, lo que podría explicar los resultados discrepantes del Estudio Di@bet.es que es un estudio poblacional en el que se incluyen personas con diabetes aleatoriamente seleccionadas dentro de la población general y no procedentes de bases de datos clínicas de personas con diabetes. Las personas con diabetes tendrían con más frecuencia trastornos del sueño porque en ellos son más frecuentes, la nicturia (necesidad de orinar por la noche); las hipoglicemias nocturnas sobre todo en pacientes con DM1 en tratamiento con insulina; el síndrome de las piernas inquietas, que se ha demostrado tres veces más frecuente en personas con DM; el síndrome de apnea nocturna del sueño (SAS), así como insuficiencia cardiaca, hipertensión arterial, accidentes cerebro vasculares o síndrome depresivo, todos ellos susceptibles de empeorar la calidad del sueño.


 ¿REPERCUTEN LOS TRASTORNOS DEL SUEÑO EN EL CONTROL METABÓLICO DE LA DM?

 Diferentes estudios han mostrado que la relación entre la calidad del sueño y la situación clínica de la diabetes siguen una relación bidireccional. Por un lado la DM, o sus complicaciones, como hemos visto arriba, pueden asociarse con trastornos del sueño, pero al mismo tiempo la presencia de trastornos del sueño, se asocia con un peor control de la diabetes mellitus, medido, por ejemplo, por los niveles de HbA1c . Esto es especialmente válido cuando existe un síndrome de apnea del sueño (SAS), habiéndose demostrado que la mayor la severidad del SAS, se asocia con un incremento de los niveles de HbA1c .

 ¿SON LOS TRASTORNOS DEL SUEÑO MÁS FRECUENTES EN LAS PERSONAS CON DM 1?

 Medidas objetivas del sueño basadas en proSueño . HORAS DE SUEÑO EN FUNCIÓN DEL METABOLISMO DE LA CHO (ESTUDIO DI@BET.ES) LA CANTIDAD Y LA CALIDAD DEL SUEÑO ES UNA VARIABLE BIOLÓGICA QUE SE PUEDE ASOCIAR CON EL RIESGO DE NUMEROSOS PROBLEMAS METABÓLICOS COMO DIABETES .  La polisomnografía muestra que niños con DM1(Diabetes Mellitus tipo 1) pasan más tiempo en la fase 2 (sueño ligero) y menos tiempo en la fase 3, comparado con niños sin DM1 . Diferentes estudios recientes muestran que la arquitectura y la calidad del sueño están con frecuencia alteradas en las personas con DM1. Estas anomalías del sueño pueden ser el resultado tanto de cambios en los patrones de comportamiento y psicológicos de las personas con DM1 así como de su tratamiento. Por otro lado el síndrome de apnea de sueño (SAS) parece ser más prevalente en personas con DM1, siendo conocida su asociación con el peor control de la DM. Finalmente en las personas con DM1 con trastornos del sueño es más frecuente la presencia de hipertensión “non dipper” (la presión arterial no desciende por la noche como seria lo habitual) .



 TRASTORNOS DEL SUEÑO EN LAS MUJERES EMBARAZADAS CON DIABETES.


 Entre el 70 % y el 94 % de las mujeres tienen dificultad en el sueño durante el embarazo, habiéndose incluido los trastornos del sueño asociados al embarazo como entidad nosológica especifica en la primera Clasificación Internacional de los Trastornos del Sueño (ICSD-1). Algunos estudios parecen mostrar que las embarazadas con diabetes gestacional poseen una peor calidad de sueño y un grado de somnolencia diurna superior al de la media poblacional, reduciéndose con ello el bienestar de la madre y del feto . Una explicación detallada de los mecanismos por los que los trastornos del sueño se pueden asociar con el riesgo de enfermedades metabólicas como la obesidad, la hipertensión, la DM o la enfermedad cardiovascular, excede de los límites de esta breve revisión, pero pueden ser consultados en la excelente presentación en internet del profesor Luis Felipe Pallardo.



 CONCLUSIÓN:

 La cantidad y la calidad del sueño es una variable biológica que se puede asociar con el riesgo de numerosos problemas metabólicos, incluido el de obesidad y diabetes, así como con el propio control de la diabetes mellitus y sobre la calidad de vida de las personas con DM. Sin embargo los clínicos le prestan poca atención y no suelen registrar esta información en la historia clínica. Los trastornos del sueño deberían ser hoy considerados como un factor de riesgo cardiometabólico y clínico. Los médicos podemos ayudar a las personas con o sin diabetes a dormir mejor. Un mejor conocimiento de los trastornos del sueño por parte de los médicos ayudaría a diseñar estrategias que contribuirían a prevenir el riesgo de enfermedades metabólicas, incluidas la obesidad y la diabetes y, sobre todo al mejor control metabólico y de sus complicaciones, así como de la calidad de vida de los pacientes. 

Fuente: Federico J.- Soriguer Escofet. Médico Academia Malagueña de Ciencias.




martes, 20 de junio de 2017

DR. BERCOVICH: BOMBA DE INSULINA DE ASA CERRADA


BOMBA DE INSULINA DE ASA CERRADA

PANCREUM




Hace tiempo ya que varias compañías trabajan en el ajuste y perfeccionamiento de la parte más complicada de una bomba de insulina de asa cerrada: los algoritmos de cálculo. Toda la programación que hace que una bomba de insulina deje de ser lo que es ahora (un dispositivo tonto) para convertirse en un dispositivo inteligente, autónomo y con capacidad de tomar decisiones, autogestionando nuestras cifras de glucemia a cada segundo. Esta es la famosa bomba de insulina de asa cerrada. Un intento tecnológico de aproximarse lo más posible al funcionamiento de un páncreas humano en lo referente a la insulina. Saber cuándo poner insulina, saber cuánta poner, saber cuándo dejar de administrarla, saber cuándo hay hipoglucemia o hiperglucemia… demasiadas variables. Pero los desarrollos están ahí y en EEUU hay ya sujetos por la calle con sus prototipos haciendo una vida normal y comprobando que esa programación funciona. Y uno de esos desarrollos es la bomba de insulina de asa cerrada Pancreum.

Su nombre ya es una declaración de intenciones. Con un prototipo físico que se puede tener en la mano (aunque no sé si operativo al 100%) y todo un esquema de funcionamiento, el vídeo que vais a ver deja con la boca abierta a cualquiera que tenga diabetes. Un dispositivo compuesto por un “núcleo” como cerebro del sistema, y al que se acoplan los 3 elementos fundamentales: una bomba de insulina, un dispositivo de medición continua de glucosa CGM y una bomba de glucagón. Entre los 3, ayudados por el soft integrado en el core, permiten a su portador olvidarse de la diabetes, ya que Pancreum se encarga de todo. ¿Suena a cuento? pues sí, pero suena a cuento celestial. Sin embargo, el diseño -premiado, por cierto- está registrado, la empresa está buscando inversores y afirman tenerlo todo listo para su producción.


Confirman la seguridad del sistema híbrido de asa cerrada de Medtronic


Un estudio publicado en el ‘Journal of the American Medical Association‘ (JAMA) ha demostrado la seguridad y eficacia del sistema híbrido de asa cerrada de Medtronic en la diabetes, ya que permite que los pacientes tengan una menor variabilidad glucémica y reduzcan su Hemoglobina Glicosilada, en comparación con los datos basales obtenidos con el uso de las bombas con sensor.
Según Richard M. Bergenstal director ejecutivo del International Diabetes Center en Minneapolis (Estados Unidos) “este gran estudio interno demostró que los participantes que tenían el sistema híbrido de asa cerrada de Medtronic estaban controlados las 24 horas del día”, especialmente por la noche, cuando resulta más complicado mantener los niveles de glucosa controlados.
El estudio sobre el sistema híbrido de asa cerrada de Medtronic es el primer ensayo clave en Estados Unidos de una tecnología de asa cerrada, y el mayor estudio local sobre asa cerrada, con una evaluación que incluye más de 12.000 días.
El sistema híbrido de asa cerrada automatiza la infusión de insulina basal a fin de mantener los niveles de glucosa en el rango objetivo el mayor tiempo posible durante el día y la noche.
Este estudio multicéntrico incluyó a 124 personas con diabetes tipo 1 con una edad mínima de 14 años en 10 centros (nueve de Estados Unidos y uno de Israel), a quienes se les pidió que introdujeran los hidratos de carbono que ingerían y la información sobre el ejercicio que practicaban y que calibraran el sensor de forma periódica.
“Estamos encantados con el progreso que hemos logrado en el control de la glucosa con el sistema híbrido de asa cerrada. Durante la fase de estudio, no se produjeron episodios de hipoglucemia severa ni de cetoacidosis en los pacientes con diabetes tipo 1 que seguían la terapia”, ha explicado el investigador principal del trabajo y director ejecutivo del International Diabetes Center en Minneapolis (Estados Unidos), Richard M. Bergenstal.
Los datos, asegura son “convincentes” y demuestran la capacidad del sistema de dosificar la insulina de forma automática y el hecho de que se simplifique el control de la diabetes.
“Tenemos el compromiso de desarrollar soluciones significativas como esta para ofrecer mayor libertad y una salud mejor, de forma que las personas con diabetes y sus cuidadores puedan dedicar menos tiempo a controlar la diabetes y más tiempo a disfrutar del día a día”, ha asegurado el presidente de Intensive Insulin Management Diabetes en Medtronic, Alejandro Galindo.




DR:BERCOVICH: HIPERGLUCEMIA EN ANCIANOS

FISIOPATOLOGIA DE LA HIPERGLUCEMIA EN ANCIANOS

CONSIDERACIONES CLINICAS

Extraído Diabetes Care 2017


The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations
1.       Pearl G. Lee1,2 and 
2.       Jeffrey B. Halter2
+Author Affiliations
1.       Corresponding authors: Pearl G. Lee, pearllee@med.umich.edu, and Jeffrey B. Halter, jhalter@med.umich.edu.
Diabetes Care 2017 Apr; 40(4): 444-452. https://doi.org/10.2337/dc16-1732
Abstract
Nearly a quarter of older adults in the U.S. have type 2 diabetes, and this population is continuing to increase with the aging of the population. Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. The usual defects contributing to type 2 diabetes are further complicated by the natural physiological changes associated with aging as well as the comorbidities and functional impairments that are often present in older people. This paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population.
Introduction
Diabetes is one of the leading chronic medical conditions among older adults, with high risk for vascular comorbidities such as coronary artery disease, physical and cognitive function impairment, and mortality. Despite decades of effort to prevent diabetes, diabetes remains an epidemic condition with particularly high morbidity affecting older adults. In fact, nearly 11 million people in the U.S. aged 65 years or older (more than 26% of adults aged 65 years or older) meet current American Diabetes Association criteria for diabetes (diagnosed and undiagnosed), accounting for more than 37% of the adult population with diabetes . At the same time, adults 65 years or older are developing diabetes at a rate nearly three-times higher than younger adults: 11.5 per 1,000 people compared with 3.6 per 1,000 people among adults aged 20–44 years old . However, increasing research in diabetes and aging has improved our understanding of the pathophysiology of diabetes and its association with aging and led to the development of a number of antihyperglycemic medications. The mechanism of diabetes complications has been previously reviewed . The current paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population.
Pathophysiology of Type 2 Diabetes
Type 2 diabetes is by far the most prevalent form of diabetes in older adults and is an age-related disorder. The criteria for diagnosing diabetes are the same for all age groups because the risks of diabetes-related complications are associated with hyperglycemia over time across all age groups . Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. These factors contribute to hyperglycemia through effects on both β-cell insulin secretory capacity and on tissue sensitivity to insulin. The occurrence of type 2 diabetes in an older person is complicated by the comorbidities and functional impairments associated with aging.
Hyperglycemia develops in type 2 diabetes when there is an imbalance of glucose production (i.e., hepatic glucose production during fasting) and glucose intake (i.e., food ingestion) as opposed to insulin-stimulated glucose uptake in target tissues, mainly skeletal muscle. Multiple factors in an older person contribute to such an imbalance of glucose regulation. Although resistance to peripheral insulin action contributes to altered glucose homeostasis, current evidence has found that the direct effect of aging on diabetes pathophysiology is through impairment of β-cell function, resulting in a decline in insulin secretion.

Genetics
There is a strong genetic predisposition to type 2 diabetes . The genetic susceptibility to type 2 diabetes is polygenic, involving a number of variants, where each allele has a modest effect on the risk of disease in an individual person. Genome-wide association studies, linkage analysis, candidate gene approach, and large-scale association studies have identified 70 loci conferring susceptibility to type 2 diabetes . These genetic alleles appear to affect the risk of type 2 diabetes primarily through impaired pancreatic β-cell function, reduced insulin action, or obesity risk.
Genome-wide association studies have consistently found that p16INK4a, a cyclin-dependent kinase inhibitor (CDKI), encoded by the Cdkn2a locus, is associated with type 2 diabetes risks . Expression of p16INK4a was increased in aging mice , and an additional copy of p16INK4awas associated with markedly reduced pancreatic islet cell proliferation . β-Cell proliferation was increased in p16INK4a knockout mice. Therefore, p16INK4a increases with age and appears to mediate an age-associated decline in the replicative capacity of mouse islets; p16INK4a could be a potential link between aging, metabolic derangements, and β-cell failure in type 2 diabetes.
Effects of Aging
Impaired Insulin Secretion, Insulin Resistance, and Their Interaction
In the setting of genetic and lifestyle-related risk factors, aging contributes to the development of type 2 diabetes through impaired β-cell function and impaired β-cell adaptation to insulin resistance  leading to impaired insulin secretion . Studies in rodents and humans have found that aging may exert a distinct influence on β-cell turnover as well as function.
In older patients who have developed diabetes, autoimmune destruction of β-cells is rarely observed. Limited pathologic investigation suggests that total β-cell mass may be moderately reduced, but severe loss of β-cell mass is uncommon. Pancreatic β-cell mass in adult humans exists in a dynamic state such that the cells can undergo compensatory changes to maintain euglycemia. Aging is thought to be associated with reduced capacity to regenerate β-cells, as suggested by studies involving rodents  and humans . On the one hand, for example, the β-cell toxin streptozotocin, partial pancreatectomy, or exendin-4 were more effective in stimulating β-cell proliferation in younger mice (younger than 12 months old) than in older mice . On the other hand, the age-associated decline in β-cell function in older rats has been shown to be reversible with glucagon-like peptide 1 (GLP-1; exendin) treatment , suggesting stimulation of β-cell regeneration . In humans, the baseline β-cell population and appropriate association with other islet cell types is established before 5 years of age . Other studies using C14 or Ki67 have found that human adult β-cell turnover is very low . Similarly among middle-aged and older adults, minimal β-cell regeneration was observed after a mean follow-up period of 1.8 ± 1.2 years after a 50% partial pancreatectomy: β-cell mass and new β-cell formation were not increased, and β-cell turnover was unchanged . The follow-up time of this study may have been too short for human β-cells to replicate, but other studies have also found evidence of slow β-cell proliferation in humans with advancing age . The decline in β-cell replication was directly associated with a decrease in the expression of a transcription factor known as the pancreatic and duodenal homeobox 1 . Thus, the overall evidence suggests that human β-cells survive for a long time and are unlikely to be replenished by replications once adulthood is reached . Several age-related potential molecular pathways have been found to restrict β-cell regeneration. For example, the replication refractory period, the time between cell divisions (G0 stage of cell cycle), appears to lengthen with age ; the replicative capacity of β-cells might be reduced due to accumulation of DNA mutations with aging.
Therefore, β-cell function in human adults might be enhanced in the setting of hyperglycemia or insulin resistance to maintain euglycemia. Pancreatic β-cells appear to primarily compensate for limited replication capacity through hyperplasia and hypertrophy. However, a number of studies have demonstrated a decline in β-cell function and insulin secretion with age in rodents . In humans, the insulin secretion rate in response to glucose was significantly and progressively decreased in older individuals, with the greatest impairment in older individuals with impaired glucose tolerance compared with older individuals with normal glucose tolerance or with younger individuals matched for degree of insulin resistance . In fact, a 50% reduction in β-cell secretory capacity has been observed in older men compared with younger men in response to arginine stimulation .

Impaired pancreatic β-cell adaptation to insulin resistance appears to be an important contributing factor to age-related glucose intolerance and risk for diabetes. Although aging per se has a minimal effect on insulin action directly , many older individuals develop insulin resistance as a result of diminished physical activity, obesity, and loss of lean body mass, particularly those with a disproportional loss of skeletal muscle over adipose tissue. Age had no independent effect on insulin sensitivity when controlled for obesity; age-related reductions in insulin sensitivity are likely the result of an age-related increase in adiposity rather than a consequence of advanced chronological age .
Insulin resistance with aging appears to reflect predominantly lifestyle factors such as poor diet and diminished physical activity. These changes lead to decreased lean body mass and increased adiposity, particularly visceral adiposity, with aging. More than 35% of U.S. adults aged 60 years or older are obese, having a BMI of 30 kg/m2 or greater. An absolute or relative increase of body adiposity, particularly central body adiposity, often associated with advancing age, appears to account in large part for the age-related increase in insulin resistance . Even among adults without diabetes, intraabdominal fat mass correlates with insulin resistance and age after controlling for obesity . However, insulin resistance is more closely associated with abdominal adiposity than with age . In addition to excessive caloric intake, increased body adiposity is partly related to a sedentary lifestyle, which is common among older adults; for example, only 12% of adults aged 75 or older engage in 30 min of physical activity 5 or more days per week, and 65% report no leisure time physical activity . Increasing physical activity in older adults reduces insulin resistance , reduces the risk of developing diabetes , and improves glycemic control in people with diabetes .
Low-grade inflammation and stress-response changes associated with obesity and aging are likely to contribute to the increased risk of type 2 diabetes among older adults . Aging and obesity are both thought to be independently associated with the development of low-grade inflammation , and proinflammatory cytokines, such as C-reactive protein, interleukin 6, and tumor necrosis factor-α, have been found to inhibit insulin signaling and increase insulin resistance and risk of type 2 diabetes.
The role of mitochondrial function in aging and type 2 diabetes remains unclear. Older adults were found to have a decrease in mitochondrial function compared with younger adults (i.e., decreased ATP synthesis); however, older adults with normal glucose tolerance had similar ATP production level compared with older adults with impaired glucose tolerance . On the other hand, exercise reverses age-related declines in mitochondrial oxidative capacity and ATP production, which may be part of the underlying mechanism through which exercise improves insulin sensitivity .
There is a maladaptive response to insulin resistance in the setting of impaired β-cell function leading to further impairment of insulin secretion and progression to impaired glucose tolerance and type 2 diabetes. Hyperglycemia, in turn, contributes directly to insulin resistance and impairs pancreatic β-cell function, effects described as glucose toxicity . Such glucose toxicity sets up a vicious cycle of maladaptive mechanisms leading to further deterioration of β-cell function and more severe insulin resistance.
Comorbidities and Their Effect on Insulin Sensitivity and Secretion
Coexisting illness is another factor that can affect insulin sensitivity and insulin secretion in an older person. Hypertension, for example, is common in older people and has been associated with diminished insulin sensitivity . Furthermore, any acute illness can precipitate hyperglycemia because of effects of stress hormones to cause insulin resistance combined with the α-adrenergic effects of catecholamines released during stressful illness to inhibit insulin secretion.
Medications used in treating chronic medical conditions may induce or increase insulin resistance or worsening hyperglycemia among patients with diabetes. Glucocorticoids, for example, promote hepatic gluconeogenesis, thus increasing hyperglycemia, and contribute to insulin resistance by increasing visceral fat and promoting proteolysis, lipolysis, free fatty acid production, and fat accumulation in the liver .
Impaired glucose regulation over time leads to overt diabetes, which in turn leads to microvascular or macrovascular complications. Diabetes-associated complications, along with other comorbidities prevalent among older adults, such as arthritis, cognitive impairment, and depression, may contribute to decreased physical activity and disability (49). All of these changes can further impair glucose regulation and adversely affect glycemic management.
Implications for Management of Type 2 Diabetes Among Older Adults
General Approach
The complexity of diabetes and its management requires a collaborative effort by a team of health care providers, which may include physicians, nurse practitioners, nurses, dietitians, pharmacists, social workers, and mental health professionals. Patients and family members must also assume an active role . When developing a treatment plan, in addition to targeting the various factors involved in the pathophysiologic pathways of type 2 diabetes, providers should address other relevant comorbid conditions that are common among older adults and can easily affect the ability of the patient to manage diabetes. Aging is associated with increasing risk of developing geriatric syndromes, such as visual impairment, cognitive impairment, and functional impairment, and diabetes is also associated with an increased risk of retinopathy and deficits in cognitive and physical functioning . Geriatric syndromes will in turn affect the ability of older adults to manage their diabetes. Such limitations may affect a patient’s ability to obtain food or medications, to exercise, or to see his or her health care providers.
Because older adults with diabetes are quite heterogeneous with respect to their health status and available care support, the goal for hyperglycemia management should be individualized based on their comorbidities and physical and cognitive function status. A comprehensive geriatric assessment will help the providers to assess an older patient’s ability to safely follow a complex diabetes treatment plan. Given that type 2 diabetes develops after years of metabolic abnormalities, a thorough medical evaluation in search for existing diabetes complications is warranted even when a new diagnosis is made in an older adult. The clinical assessment is used to recommend individualized glycemic, blood pressure, and lipid goals for older adults with diabetes. An interdisciplinary expert panel that included geriatricians, endocrinologists, and other diabetes health care providers was convened by the American Diabetes Association at a Consensus Development Conference on Diabetes and Older Adults in 2012. This group developed a framework to set diabetes treatment goals based on individual patients’ comorbidities and physical and cognitive function status .
Lifestyle Interventions
Lifestyle interventions, including regular physical activity and mild-moderate weight loss, are the first-line intervention for diabetes prevention and for treatment of hyperglycemia in older people. Lifestyle interventions are particularly effective in reducing the risk of developing diabetes among older adults  and are also beneficial in improving diabetes management among older adults . Lifestyle interventions can reduce insulin resistance and thereby help reverse the vicious cycles . However, there is no evidence that lifestyle interventions can reverse the effects of aging on β-cells; thus, such interventions may delay, but are not likely to completely prevent, the ultimate development of hyperglycemia.
Physical Activity
Regular physical activities for older adults with diabetes, particularly activities of moderate to vigorous intensity, can improve insulin sensitivity . Regular physical activities are a useful adjunct to drug therapy to manage glucose levels and may well contribute to enhanced effectiveness of glucose-lowering agents. Furthermore, increasing physical activity as part of a lifestyle intervention is effective in reducing physical functioning impairment among patients with diabetes, improving glucose, lipid, and blood pressure control, and enhancing weight loss .
Traditionally, aerobic training activities have been recommended for older adults, given their benefits in cardiorespiratory fitness. Evidence also supports regular whole-body resistance training for older adults with type 2 diabetes. As previously discussed, the pathophysiology of type 2 diabetes involves insulin resistance, and the main tissues in the body that are sensitive to insulin are muscles and adipose cells. Resistance training changes body composition (e.g., increases skeletal muscle mass), improves insulin sensitivity, and reduces HbA1c .
In fact, physical activity programs that include both aerobic and resistance training improve glycemic levels more than aerobic or resistance training alone . Thus, the American Diabetes Association recommends that all adults with diabetes should perform at least 150 min/week of moderate-intensity aerobic physical activity, spread over at least 3 days/week with no more than 2 consecutive days without exercise. As part of the exercise routine, resistance training should be performed at least twice weekly .
Given the high prevalence of coronary artery disease in older patients with diabetes, which may be asymptomatic or atypical in symptoms, it is important for such patients to have medically supervised stress testing before entering any challenging exercise training program. Additional issues to consider in an older person participating in an exercise program include the potential for foot and joint injury with upright exercise, such as jogging, unstable comorbidities, autonomic neuropathy, peripheral neuropathy, or foot lesions that may predispose to injures, and the ability to promptly identify and treat hypoglycemia, which can be induced by exercise if the patient is on insulin or a sulfonylurea. Therefore, each patient’s exercise prescription needs to be individualized based on his or her capability to safely participate in an exercise program.
Obesity and Diet
Even a modest to moderate body weight loss (5–10% of initial body weight) increases insulin sensitivity and improves glucose tolerance in obese individuals as well as in those with impaired glucose tolerance or type 2 diabetes . As part of diabetes management, the American Diabetes Association recommends that overweight adults with type 2 diabetes lose 2–8 kg weight through lifestyle changes . Recent studies have not substantiated previous concerns about the risks of weight loss among older adults, where older adults who intentionally lost weight by combining caloric restriction and exercise had minimal reduction in lean muscle mass and actually had increased bone density and improvement in physical function compared with individuals who lost weight by caloric restriction alone or by exercise alone . Hence, weight loss programs for older adults with diabetes should incorporate caloric restriction with physical activity.
Caloric restriction is appropriate for healthier overweight and obese older diabetes patients as part of management of hyperglycemia but is not appropriate for some older patients who are at risk for undernutrition already. More pressing dietary issues for these patients are how to maintain adequate caloric intake and coordinate food intake with administration of glucose-lowering agents appropriately to avoid hypoglycemia. Older adults with mobility limitation or who lack transportation are likely to have limited access to healthy and fresh food . Social isolation (i.e., living alone, eating alone), poverty, and functional reliance on others to purchase food are all risk factors for decreased food intake. The presence of impaired cognitive function may make following a dietary prescription particularly difficult. Furthermore, dietary habits established for a lifetime and often with a cultural background may be particularly difficult to modify. Problems with taste and oral health, which are common in older people, may further limit adaptation to a prescribed diet . Oral health problems can be exacerbated by diabetes, which may increase the rate of periodontal disease. Xerostomia is also more common in older people owing to decreased salivary gland flow and is sometimes exacerbated by coexisting medication use.
Medications in the Management of Hyperglycemia
Most medications to treat hyperglycemia in older adults with type 2 diabetes target one or more of the pathophysiological impairments of age-related type 2 diabetes: reducing hepatic glucose production, increasing insulin secretion, increasing insulin sensitivity, decreasing glucagon secretion, increasing incretin levels, and decreasing satiety. Unfortunately, older patients are often underrepresented in large clinical trials; therefore, data on antihyperglycemic medications are often extrapolated from younger populations .
Treatment of older adults with diabetes needs to account for the progression of type 2 diabetes over time . Because of the age-related decline of β-cell function, maintaining target levels of glycemic control may necessitate escalation of drug doses or the addition of other antihyperglycemic agents . Thus, medications that target the β-cells, such as sulfonylureas or GLP-1–related drugs, are likely to become less effective over time. Medications such as metformin, thiazolidinediones (TZDs), and sodium glucose transporter 2 (SGLT2) inhibitors may help to reverse some of the vicious cycles contributing to hyperglycemia but do not directly address the effects of aging on β-cells.
Treatment choices should be tailored to the specific situation of the individual patient, as determined in part by the initial comprehensive assessment of the patient’s comorbidities, cognition, functional status, care support, and financial situation . Although it is common for an older adult to have multiple comorbidities, impairment in cognition or functional status, and limited financial support, a strong supportive care system may be sufficient to help the patient to safely implement a complex medical treatment.
The treatment plan should minimize risk for hypoglycemia, especially in frail, vulnerable older patients and when using agents with high risk for hypoglycemia such as insulin and sulfonylureas. Thus, emphasis on lifestyle interventions and classes of drugs that do not cause hypoglycemia can often result in safe achievement of lower A1C targets, especially early in the course of type 2 diabetes. As these safer interventions become less effective as a result of progressive β-cell failure with aging, insulin may be needed, and the A1C target may need to be higher to avoid hypoglycemia. Sulfonylurea drugs should be used only with extreme caution in any vulnerable older patient. Frequent follow-up should be provided to ensure that the treatment program is progressing smoothly and that hypoglycemia does not occur.
Biguanides
Metformin, a biguanide, is the first-line oral medication for hyperglycemia for older adults . Because metformin’s mechanism of action predominately involves reducing hepatic glucose production, it rarely causes hypoglycemia when used alone. Some older patients may experience intolerable gastrointestinal discomfort, decreased appetite, and modest weight loss associated with metformin.
Metformin is contraindicated in patients with renal insufficiency, and the U.S. Food and Drug Administration recommends against the use of metformin in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2. Furthermore, metformin is recommended to be discontinued at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2, and can be restarted if the eGFR is stable 48 h after the imaging procedure.
Sulfonylureas
Sulfonylureas are probably overused in older adults with type 2 diabetes. These drugs are inexpensive, and their overall safety record is good. Their primary mechanism of action is to enhance insulin secretion by β-cells of the pancreas. Hypoglycemia is a serious risk, however, and conservative use is thus recommended for older people. Glyburide is associated with a high risk for hypoglycemia in older patients due to its long half-life so is not recommended in this population. Other sulfonylureas may be safer to use in older patients, but all have a hypoglycemia risk. Another concern about use of sulfonylurea drugs in older adults is a higher secondary failure rate than other drugs, probably related to progressive β-cell dysfunction .
TZDs
TZDs improve insulin sensitivity in skeletal muscle, reduce hepatic glucose production, and have the advantages of low risk for hypoglycemia. However, concerns over potential adverse effects associated with TZDs have been raised, including increased risks of bladder cancer, weight gain, fluid retention, and bone fractures . TZDS are usually not considered as first-line antihyperglycemic agents.
GLP-1 Agents
GLP-1 is an incretin, an intestinal hormone that is released as glucose levels increase with meals and cause glucose-dependent insulin secretion; therefore, GLP-1 agents are unlikely to cause hypoglycemia. Two classes of GLP-1 drugs are used clinically:
1.       The injectable GLP-1 receptor agonists stimulate insulin section in a glucose-dependent fashion, suppress glucagon output, slow gastric emptying, and decrease appetite. These agents have the advantages of modest weight loss, but for some patients, the weight loss can be too much and there may be resistance against performing injections.
2.       The oral dipeptidyl peptidase-4 (DPP-4) inhibitors enhance circulating concentrations of active GLP-1.
When used alone, both classes of GLP-1 agents rarely cause hypoglycemia, but high cost may be prohibitive for some older adults. Pilot studies of myocardial ischemia and animal studies suggested that GLP-1 agonists may improve cardiovascular outcomes, but the results from two recent large trials are mixed. Among patients with type 2 diabetes and high cardiovascular risk, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was lower with liraglutide than with placebo, but among patients with type 2 diabetes and recent acute coronary syndrome, no significant effect on the rate of major cardiovascular events was found with lixisenatide compared with placebo.
SGLT-2 Inhibitors
SGLT-2 inhibitors allow the kidneys to reabsorb most filtered glucose. SGLT-2 is found only in the proximal tubule of the kidney and accounts for 90% of the reabsorption of glucose. SGLT-2 inhibitors are oral agents that lower glucose levels by increasing urinary excretion of glucose. They are approved for use in both type 1 and type 2 diabetes. They are used once daily, result in modest lowering of A1C similar to DPP-4 inhibitors, and rarely cause hypoglycemia. They are contraindicated in chronic kidney disease. These agents increase urine volume and sodium excretion, so usually lower blood pressure modestly but may cause volume depletion. This volume effect may contribute to increased risk for diabetic ketoacidosis in people with type 1 diabetes. There is increased risk for genital yeast infection and urinary tract infection, likely resulting from the induced glycosuria. Because of these adverse effects, relatively high cost, and limited experience with these drugs in older adults, their use is usually reserved for situations in which other classes of drugs are not tolerated.
Insulin
Because β-cell dysfunction plays a major role in type 2 diabetes in older adults, insulin replacement therapy may be necessary to achieve the goal for hyperglycemia control, especially in patients with longer duration of type 2 diabetes with progressive β-cell dysfunction. The approach to use of insulin in older adults with type 2 diabetes is to start with a once-daily, long-acting insulin (basal insulin), with minimal peak or trough effect. Long-acting agents, such as insulin glargine 100 and detemir insulin, have a lower incidence of nocturnal hypoglycemia than shorter-acting insulin agents, even among older adults .
Premeal injections of a rapid-acting insulin analog can be added to the basal insulin, if necessary, in older patients in whom the physician has determined can safely administer insulin and monitor for hypoglycemia. Insulin aspart and insulin lispro have a very rapid onset and short duration of action and are used just before meals. They are less likely to result in postmeal hypoglycemia than human regular insulin . These rapid-acting insulin agents can be given within 20 min after starting a meal, and hence, are particularly useful in older patients who may not eat regularly.
Combination Therapy
Use of combination antihyperglycemic agents in older patients may be necessary with the progression of the disease. Combinations of different classes of drugs are theoretically attractive because their different modes of action address various aspects of the pathophysiology of hyperglycemia. For older patients who have persistent hyperglycemia (above their individualized A1C target) with lifestyle intervention and metformin (if not contraindicated), adding another agent would be recommended. The options include adding an oral agent such as short-acting sulfonylurea (i.e., glipizide), DPP-4 inhibitors , or SGLT2 inhibitors . Alternatively, a basal insulin, such as glargine, may be added . If a sulfonylurea is already being used, we would recommend tapering it to discontinue because a combination of sulfonylurea and insulin greatly increases the risk of hypoglycemia .
Conclusions

Older adults are at high risk for the development of type 2 diabetes as a result of the combined effects of genetic, lifestyle, and aging influences. Despite the advancement in understanding the pathophysiology of type 2 diabetes, more research is needed to elucidate the underlying molecular mechanisms of how aging is related to type 2 diabetes and to diabetes-related complications . Prevention of type 2 diabetes and treatment of hyperglycemia in older adults should emphasize lifestyle interventions based on the pathophysiology of the development of type 2 diabetes and their numerous benefits on the overall health of older adults. With the aging of β-cell function, the addition of one or more medications to achieve glycemic control targets may be needed. However, the overall management of hyperglycemia needs to be individualized for older adults based on individuals' likelihood of benefiting from tight control versus the risks associated with implementing complex management regimens, especially when insulin or a sulfonylurea drug is included. A comprehensive assessment involving the individual’s comorbidities and geriatric syndromes, including cognitive and functional status, can help tailor the treatment plan.