FACULTAD DE CIENCIAS DE LA SALUD CARRERA PROFESIONAL DE MEDICINA HUMANA “Efectos del ejercicio aeróbico sobre los componentes del síndrome metabólico en adultos mayores con diabetes mellitus tipo 2: Revisión sistemática” Tesis para optar el título profesional de: MÉDICO CIRUJANO Presentado por: Mercedes Miranda Tueros: (0000-0001-5894-6497) Joshua Jimmy Rony Ramirez Peña: (0000-0001-7219-4949) Asesor: Isabel Angelica Pinedo Torres: (0000-0003-4618-5103) Lima – Perú 2022 Declaración de impacto: Esta revisión sistemática aporta una visión completa y actual de los efectos del ejercicio aeróbico sobre los componentes del síndrome metabólico en la población diabética geriátrica, así como contribuye a que futuras investigaciones se centren en este grupo y tipo de ejercicio específico ya que, como se ha visto en nuestra revisión sistemática, es una estrategia beneficiosa. Certificamos que este trabajo es novedoso ya que no ha habido una revisión sistemática previa sobre esta población asociada al ejercicio aeróbico. Resumen Antecedentes: Se recomienda la actividad física para mejorar los parámetros metabólicos de los pacientes diabéticos, sin embargo, no existe consenso sobre cuáles podrían ser los efectos potenciales del ejercicio aeróbico sobre el perfil metabólico en los adultos mayores diabéticos, por lo que realizamos una revisión sistemática y metaanálisis. Métodos: Utilizamos las bases de datos PubMed/Medline, Scopus, Cochrane library, Web of Science y el buscador, Google Scholar. Se seleccionaron los ensayos controlados aleatorizados (ECA) según los criterios de inclusión. Dos revisores determinaron de forma independiente si los estudios cumplían con los criterios de inclusión, extrajeron los datos y utilizaron la herramienta Cochrane de riesgo de sesgo (ROB). Los análisis cuantitativos se realizaron en R V. 4.0.5 utilizando efectos aleatorios. Resultados: Las búsquedas identificaron 8697 estudios, de los cuales 7 ECA se incluyeron en la síntesis cualitativa. Se evaluó que la mayoría de los estudios tenían un ROB alto o bajo en al menos tres dominios. El metaanálisis mostró que el ejercicio aeróbico fue eficaz para mejorar los niveles de glucosa (diferencia de medias estandarizada [SMD]: -1,04; intervalo de confianza [IC] del 95 %: -1,27; -0,81), presión arterial sistólica ([SMD]: -0,79 ; [IC]: -1,02; -0,56), presión arterial diastólica ([SMD]: -0,75; [IC]: -0,98; -0,52), hemoglobina glucosilada ([SMD]: -0,57; [IC]: -0,77 ; -0,37), HDL ([SMD]: 0,35; [IC]: 0,15; 0,55), triglicéridos ([SMD]: -0,26; [IC]: -0,47; - 0,06). No se informaron efectos adversos significativos. Conclusiones: El ejercicio aeróbico demostró tener una mejoría significativa en los componentes del síndrome metabólico en adultos mayores diabéticos y no se reportaron efectos adversos importantes. Sin embargo, recomendamos más ECA que tengan un mayor tiempo de intervención para establecer el impacto sobre los síntomas y las complicaciones. Palabras c lave Exercise, Diabetes Mellitus, Aged, Systematic Review, Metabolic Syndrome. INTRODUCCIÓN Se estima que para el año 2050, la población de adultos mayores será el doble que la del censo del año 2019, por lo que una de cada 6 personas en el mundo tendrá 65 años o más1. Además, patologías como la diabetes mellitus tipo 2 (DT2) y el síndrome metabólico acompañan a esta población 2,3 Estas dos condiciones están estrechamente relacionadas y ambas aumentan el riesgo de complicaciones cardiovasculares fatales a corto plazo, como isquemias cardiacas o enfermedad cerebrovascular4,5. Actualmente, las guías disponibles recomiendan la actividad física junto con la dieta y la medicación para mejorar los parámetros glucémicos y lipídicos en pacientes con diabetes 6,7. Dentro del entrenamiento físico, existen varios tipos de ejercicios de utilidad demostrada, entre los que destacan el ejercicio aeróbico, de resistencia y el ejercicio de alta intensidad con bajo volumen 8,9. El ejercicio aeróbico ha sido el más estudiado y se define como cualquier trabajo que desarrolle la aptitud cardiovascular y pulmonar, utilizando el oxígeno como sustrato metabólico 10. Esto incluye entrenamientos de diferentes intensidades, desde caminar a paso ligero hasta trotar, andar en bicicleta o nadar 10,11. Se ha informado que este tipo de ejercicio conduce a diferentes beneficios, como una mejora en la sensibilidad a la insulina, aumento de la fibrinólisis, disminución de los triglicéridos y la presión arterial, todo lo cual mejora el pronóstico de un paciente con diabetes 12–15. A pesar de estos amplios beneficios, el ejercicio físico no se puede prescribir sin restricciones. La población adulta mayor se caracteriza por tener en la mayoría de los casos limitación de movilidad, obesidad, discapacidad visual o enfermedad cardiovascular, sin mencionar que a la población geriátrica con diagnóstico de diabetes, se le suma un mayor riesgo de hipoglucemia y síndrome de fragilidad 16–19. Y, aunque las pautas de la guía “Physical Activity Guidelines for Americans”20 recomiendan que los adultos mayores de 65 años realicen al menos 150 min de actividad física aeróbica de intensidad moderada o 75 min de actividad física aeróbica de intensidad vigorosa por semana, los efectos potenciales del ejercicio aeróbico sobre los agentes metabólicos marcadores para el control adecuado de la diabetes en personas mayores y la seguridad de su prescripción no se conocen completamente 21. Se realizó una revisión sistemática con metaanálisis para evaluar los efectos del ejercicio aeróbico en adultos mayores diagnosticados con diabetes sobre los componentes del síndrome metabólico. Esto proporcionará a los médicos y especialistas una visión general de la evidencia científica sobre una posible opción de tratamiento, que ayudará en el manejo de esta población. METODOS Esta revisión sistemática se realizó de acuerdo con las directrices “Systematic Reviews and Meta-Analyses (PRISMA) 2020”. El protocolo fue registrado en PROSPERO con el número de CRD42021250115. Criterios de inclusión Se seleccionaron los ensayos clínicos aleatorizados (ECA) que incluyeron los siguientes a) pacientes con DT2, b) que evaluaron a adultos mayores (mayores de 60 años), c) con texto completo disponible y d) y cuya intervención fuera cualquier tipo de ejercicio aeróbico durante un tiempo mínimo de 12 semanas en comparación con el estándar de atención o ninguna intervención. La definición de ejercicio aeróbico se consideró de acuerdo con las pautas de guía “Physical Activity Guidelines for Americans” realizadas por el Departamento de Salud y Servicios Humanos de los Estados Unidos 20. Se tuvo en cuenta la intensidad del ejercicio según lo recomendado 11. Se excluyó cualquier otro tipo de publicación (cartas al editor, reporte de casos, estudios observacionales, revisiones narrativas y sistemáticas). Estrategia de búsqueda Se realizó una búsqueda sistemática en las siguientes bases de datos: Pubmed/Medline, Scopus, Web of Science, Cochrane Central y, finalmente, y el buscador Google Scholar para literatura gris; de 2011 al 5 de febrero de 2021. La estrategia de búsqueda incluyó términos de Medical Subject Headings (MeSH) y palabras relacionadas para "Diabetes mellitus" y "ejercicio" o "entrenamiento aeróbico". Se puede revisar en el anexo 1. No se hicieron restricciones con respecto al idioma o área geográfica. Selección de estudios y extracción de datos Los resultados de la búsqueda electrónica se importaron al programa de gestión de referencias EndNote X9; seguido de esto, se eliminaron los registros duplicados de acuerdo con los procedimientos descritos por Bramer et al22. Posteriormente, dos autores (MMT y JRP) examinaron de forma independiente los títulos y resúmenes de acuerdo con los criterios de inclusión y exclusión. Se seleccionaron los estudios relevantes y se realizaron búsquedas de textos completos para una evaluación adicional. Las discrepancias en las selecciones se resolvieron por consenso y, en última instancia, se consultó a un tercer autor (IPT). La lista completa de artículos excluidos en esta etapa del texto completo está disponible en el anexo 2. Dos autores (JRP y MCL) extrajeron de forma independiente los datos de cada artículo incluido utilizando un formulario estandarizado en Microsoft Excel. Un tercer autor verificó la exactitud de los datos antes del análisis. Para los resultados dicotómicos, se extrajeron las frecuencias absolutas y relativas. Para los resultados continuos, se extrajeron las mediciones basales y de seguimiento, así como el cambio entre ellas. Resultados Los resultados primarios fueron los componentes del síndrome metabólico según la Federación Internacional de Diabetes (FID) 23, glucosa en ayunas (mg/dl), presión arterial sistólica (PAS, mmHg), presión arterial diastólica (PAD, mmHg), lipoproteínas de alta densidad (HDL, mg/dl), triglicéridos (mg/dl) y circunferencia de la cintura (cm/pulgada). También se consideró la hemoglobina glicosilada (HbA1c, %) debido a la importancia clínica que representa. Para interpretar el tamaño del efecto, se utilizaron las reglas de Cohen. 24 Análisis por subgrupos El análisis de subgrupos consistió en la intensidad del ejercicio, si hubo supervisión del ejercicio o no, y la duración total en horas (>30 horas y ≤ 30 horas). En caso de intensidad se dividió en Alta o vigorosa (≥ 6 METS, frecuencia cardíaca máxima ≥ 70%), Baja o moderada (<6 METS, Frecuencia cardíaca máxima <70%) 11 y no reportada. Evaluación del riesgo de sesgo Los ensayos clínicos aleatorizados se evaluaron mediante la Herramienta Cochrane de Riesgo de Sesgo para Ensayos Aleatorios (RoB 2) 25. Esta herramienta evalúa varios dominios de los que puede haber surgido el sesgo: proceso de asignación al azar, desviaciones de las intervenciones planificadas (efecto de la asignación de la intervención), datos de resultado faltantes, medición de resultados y selección de resultados informados. El riesgo de sesgo por dominio sigue un algoritmo basado en el juicio para concluir si existe bajo riesgo, algunas preocupaciones o el alto riesgo por dominio y ensayo. Un ECA con un alto riesgo de sesgo en cualquier ítem se consideró en alto riesgo de sesgo. La evaluación RoB 2.0 fue realizada de forma independiente por dos autores (MCL, MMT), y las discrepancias se resolvieron mediante discusión o consultando a un tercer autor (IPT). Análisis estadístico Todos los metaanálisis se realizaron utilizando el método de varianza inversa y el modelo de efectos aleatorios. La varianza entre los estudios (τ2) se estimó mediante con la herramienta DerSimonian-Laird. El efecto agrupado de cada resultado se determinó mediante la diferencia de medias estandarizada (DME) de los valores de cambio entre los grupos de intervención y control con los intervalos de confianza (IC) del 95%. Para los ECA que no informaron desviaciones estándar para la diferencia de medias, se realizó una imputación a partir de otros estudios disponibles, tal como recomienda el Manual Cochrane26. La heterogeneidad entre los estudios se evaluó mediante la estadística I2. La heterogeneidad se definió como baja si I2 <30%, moderada si I2 = 30-60%, y alta si I2> 60%. Todo lo anterior se presentó como un gráfico “Forest plot” para cada resultado. Para investigar la fuente de heterogeneidad, el análisis de subgrupos se consideró por separado para cada subgrupo y se realizó de acuerdo con la intensidad del ejercicio, la supervisión del rendimiento del ejercicio y el tiempo total de intervención. La función de metacont del meta-paquete en R 4. Se utilizó 0,5 (www.r-project.org). Certeza de la evidencia Se utilizó el enfoque de Evaluación, Desarrollo y Desarrollo de la Calificación de las Recomendaciones (GRADE)27 para evaluar la calidad de la evidencia para todos los resultados. Al utilizar la metodología GRADE, se consideraron los siguientes criterios para evaluar la calidad de los estudios: riesgo de sesgo, inconsistencia, imprecisión, sesgo de publicación, gran magnitud del efecto, gradiente dosis- respuesta, efecto de la confusión residual plausible y que tan indirecto sea. Generamos la tabla Resumen de Hallazgos (SOF) utilizando el software GRADE pro. Consideraciones éticas Se trata de una revisión sistemática de información publicada y abierta en la que no participaron sujetos humanos. La aprobación de un comité de ética no era necesaria. No hubo manipulación de datos, y se evaluó a través de etapas para asegurar la fidelidad de los datos presentados en este estudio. RESULTADOS Se identificaron un total de 8697 resúmenes en las bases de datos y se eliminaron 3.193 duplicados. Después de evaluar por título y resumen, se dejaron 305 para la evaluación a texto completo. Finalmente, 7 artículos cumplieron con los criterios de inclusión, el proceso de selección completo se puede encontrar en la Figura 1. Figura 1. Diagrama de selección de estudios PRISMA. Características de los estudios incluidos Las principales características de los 7 estudios se resumen en el anexo 3. Se evaluaron un total de 386 participantes. La edad media osciló entre 62,9 y 73,2 años. Dos estudios procedían de Canadá. Corea, España, Irán, China y Egipto tuvo un estudio. En cuanto al tipo de intervención, todos los estudios 28–34 utilizaron una caminadora o la actividad de caminar. La duración de la intervención varió de 12 a 24 semanas y entre los que informaron la intensidad del ejercicio, 50% fueron de alta intensidad. Entre los 7 ensayos incluidos, 1ensayo 30 demostró un alto riesgo de sesgo en general (anexo 4). Resultados primarios Entre los 7 ensayos, los metanálisis realizados para cada resultado son los siguientes: Con respecto a la glucosa en ayunas, en 5 ECA 28–30,32,33,35,36, incluidos 259 participantes, el ejercicio aeróbico redujo significativamente los valores de glucosa ([DME]: -1,76; IC del 95%: -2,78; -0,74; I2 = 91%) en comparación con el grupo control (Figura 2A). En relación con la hemoglobina glicosilada, 4 ECA 30–32,34–37, incluyeron a 288 participantes, el ejercicio aeróbico redujo significativamente los valores de HbA1c ([DME]: -0,63; IC del 95%: -0,87; -0,39; I2 = 0 %) en comparación con el grupo control (Figura 2B). Figura 2. Diferencia de medias estandarizada entre el ejercicio aeróbico y los grupos de control, un metanálisis del modelo de efectos aleatorios. (A) Glucosa en sangre en ayunas; (B) Hemoglobina glicosilada. DE: desviación estándar, DME: diferencia de medias estandarizada, IC: intervalo de confianza Con respecto a la presión arterial sistólica, en 4 ECA incluyendo 220 participantes, el ejercicio aeróbico redujo significativamente los valores de PAS ([DME]: -1,67; IC del 95%: -2,74; -0,61; I2 = 90%) en comparación con el grupo control (Figura 3A). En cuanto a la presión arterial diastólica, en 4 ECA 28,29,31,34,35,38 que incluyeron 220 participantes, el ejercicio aeróbico redujo significativamente los valores de PAD ([DME]: -1,47; IC del 95%: -2,34; -0,60; I2 = 86%) en comparación con el grupo control (Figura 3B). Figura 3. Diferencia de medias estandarizada entre el ejercicio aeróbico y los grupos de control, un metanálisis del modelo de efectos aleatorios. (A) Presión arterial sistólica; (B) Presión arterial diastólica DE: desviación estándar, DME: diferencia de medias estandarizada, IC: intervalo de confianza Con respecto a los niveles de HDL, en 5 ECA , incluidos 319 participantes, el ejercicio aeróbico aumentó significativamente sus valores ([DME]: 0,41; IC del 95%: 0,11; 0,72; I2 = 41% ) en comparación con el grupo control (Figura 4A). Con respecto a los niveles de triglicéridos, en 5 ECA 30–35incluyendo 319 participantes, el ejercicio aeróbico redujo significativamente los valores de triglicéridos ([DME]: -0,34; IC del 95%: -0,67; -0,01 ; I2 = 48%) en comparación con el grupo control (Figura 4B). Figura 4. Diferencia de medias estandarizada entre el ejercicio aeróbico y los grupos de control, un metanálisis del modelo de efectos aleatorios. (A) Lipoproteína de alta densidad; (B). Triglicéridos DE: desviación estándar, DME: diferencia de medias estandarizada, IC: intervalo de confianza No se realizó un metanálisis de la circunferencia de la cintura ya que solo se encontró 1 ECA 33, sin embargo, hubo una reducción significativa entre el grupo de ejercicio aeróbico y el grupo de control (p <0,001). Con respecto al análisis de sensibilidad, ningún estudio individual afectó significativamente el resultado agregado en ningún resultado. (anexo 5). Efectos adversos Dos de los siete ensayos reportaron algunos efectos adversos (anexo 3). Madden et al 29 reportaron un caso de síncope a masaje carotídeo, esto ocurrió tanto antes de la realización del ejercicio como una vez que se completó. Parra-Sanchez et al 31 reportaron un caso de esguince en el grupo de intervención, y dos accidentes cerebrovasculares, uno en el grupo de intervención y el otro en el grupo de control. Análisis por subgrupos Se realizó un análisis de subgrupos para evaluar los resultados en base a algunas variables como la intensidad del ejercicio, la supervisión del rendimiento del ejercicio y el tiempo total de la intervención (Anexo 6). Con respecto a los niveles de glucosa en ayunas, la presión arterial sistólica y diastólica, todos los subgrupos fueron estadísticamente significativos, excepto los ensayos que no informaron la intensidad del ejercicio. Con respecto a la disminución de los triglicéridos, los ensayos que no informaron la intensidad del ejercicio, aquellos con una duración total de la intervención menor o igual a 30 horas, y aquellos con o sin la supervisión del cumplimiento del ejercicio no tuvieron diferencias estadísticamente significativas entre la intervención y el grupo control. Acerca de la elevación del HDL, sólo los ensayos que no supervisaron el rendimiento del ejercicio tienen una diferencia estadísticamente significativa entre el grupo de intervención y el grupo de control. En cuanto a la disminución de la HbA1c, todos los subgrupos fueron estadísticamente significativos. GRADE Resumen de los hallazgos El enfoque GRADE mostró evidencia de certeza muy baja en la mayoría de los resultados primarios, excepto la presión arterial diastólica y sistólica, que tuvo una certeza moderada de la evidencia, y la glucosa en ayunas que tuvo una certeza alta de la evidencia. (Tabla 1). Tabla 1. Summary of findings. Aerobic exercise compared to control for components of metabolic syndrome in the elderly Patient or population: components of metabolic syndrome in the elderly Setting: Intervention: aerobic exercise Comparison: control Anticipated absolute № of Relative Certainty of effects participants effect Outcomes the evidence (studies) (95% Risk Risk difference (GRADE) Follow-up CI) with with aerobic control exercise SMD 1.76 SD 259 ⨁⨁⨁⨁ lower fasting glucose (FG) - - (5 RCTs) Higha,b,c (2.78 lower to 0.74 lower) systolic blood SMD 1.67 SD pressure (SBP) 220 ⨁⨁⨁◯ lower - - follow-up: mean 3 (4 RCTs) Moderatea,c,d (2.74 lower to months 0.61 lower) diastolic blood SMD 1.47 SD pressure (DBP) 220 ⨁⨁⨁◯ lower - - follow-up: mean 3 (4 RCTs) Moderatea,c,e (2.34 lower to months 0.6 lower) high-density SMD 0.41 SD lipoproteins (HDL) 319 ⨁◯◯◯ higher - - follow-up: mean 3 (5 RCTs) Very lowa,c,f (0.11 higher to months 0.72 higher) SMD 0.34 SD triglycerides (TG) 319 ⨁◯◯◯ lower follow-up: mean 3 - - (5 RCTs) Very lowa,c,f (0.67 lower to months 0.01 lower) Glycosylated SMD 0.63 SD hemoglobin (GH) 288 ⨁◯◯◯ lower - - follow-up: mean 3 (4 RCTs) Very lowa,c,f (0.87 lower to months 0.39 lower) *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; SMD: standardized mean difference GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. Explanations a. Most studies has "some concerns" in domain one b. The value of I2 is 91% on this outcome c. Different type and duration of interventions d. The value of I2 is 90% on this outcome e. The value of I2 is 86% on this outcome f. Imprecise confidence intervals DISCUSIÓN Esta revisión sistemática proporciona una visión completa y actual de los efectos del ejercicio aeróbico sobre los componentes del síndrome metabólico en la población geriátrica. Se encontró una disminución significativa en la glucosa en ayunas, la hemoglobina glicosilada, los triglicéridos, la PAS, la PAD y el aumento de los valores de HDL. Además, 4 de los 386 participantes en el estudio presentaron eventos adversos y 1 participante del grupo de intervención el evento fue grave (accidente cerebrovascular). Sin embargo, la mayoría de los resultados primarios evaluados tuvieron evidencia de certeza muy baja o baja, excepto la glucosa en ayunas y la presión arterial. De la síntesis de 5 ECA hemos obtenido que los valores de glucosa disminuyeron con la práctica de ejercicio aeróbico, nuestros hallazgos fueron similares a los reportados por la Kumar et al. 39 en donde se evaluaron 11 ensayos clínicos con una población adulta de pacientes diabéticos, encontrando una disminución tanto en la glucosa en ayunas como en la hemoglobina glicosilada. Estos resultados pueden explicarse por el hecho de que una rutina de entrenamiento frecuente mejora el rendimiento hepático al reducir la acumulación de lípidos, mejorar la resistencia a la insulina en este órgano y disminuir la producción nocturna de glucosa hepática 40 junto con una mayor actividad de las enzimas mitocondriales (mejorando así la energía muscular) 41. Cuando la medición del control glucémico es con hemoglobina glicosilada, los resultados de la síntesis de 4 ECA en nuestra revisión, así como otras revisiones sistemáticas de similares características, son consistentes. Una revisión sistemática de Pan, et al 42 con una población similar a la nuestra reportó resultados que el ejercicio aeróbico supervisado tuvo un mayor efecto en la hemoglobina glicosilada en comparación con el ejercicio de resistencia o combinado. Además, un metaanálisis de Gao et al 43 con 972 participantes informó una diferencia de medias de -0,46 en A1c a favor de la intervención. El macronutriente utilizado para obtener energía depende de la duración e intensidad del entrenamiento: se utiliza más glucosa durante el ejercicio de alta intensidad, mientras que la oxidación de ácidos grasos aumenta durante el ejercicio de intensidad moderada 44. En cuanto al metabolismo lipídico, nuestra revisión sintetizó el resultado de 5 ECA, muchos de los estudios refuerzan la relación entre el ejercicio aeróbico y la tendencia a normalizar los valores de lípidos y lipoproteínas, demostrando que la intervención aumenta los valores de HDL y disminuye los triglicéridos. Estos resultados están respaldados por diferentes revisiones como Schwingshacklet al.45, donde la práctica de diferentes tipos de ejercicio durante 8 semanas ayuda a mejorar todos los componentes de la dislipidemia en especial es ejercicio combinado. El aumento de HDL en el ejercicio podría explicarse por la asociación entre el ejercicio aeróbico y el aumento de la actividad de la lipoproteína lipasa, lo que se traduce en un aumento de la lipólisis de lipoproteínas ricas en triglicéridos, que puede ser un paso inicial en los niveles más altos de HDL sérico. Además de lo anterior, hay una reducción en la actividad de la lipasa hepática y la concentración sérica de proteína de transferencia de éster colesterilo (CETP), siendo esta última la que cataliza el flujo de transformación del colesterol HDL al colesterol VLDL y colesterol LDL 46. A partir de la síntesis de 4 ECA se informa que los valores de presión arterial sistólica y diastólica disminuyen con el ejercicio aeróbico. En este sentido, Punia et al 47 quienes evaluaron el efecto del ejercicio aeróbico en adultos de la India encontraron que disminuye significativamente la PAS y la PAD. El mecanismo por lo que esto sucede es dado por una disminución de los valores de presión arterial sistólica y diastólica en el período posterior al entrenamiento debido a una reducción de la resistencia vascular periférica 14, sin embargo otro estudio menciona que hasta ahora los mecanismos por los cuales el ejercicio reduce la presión arterial son inciertos, pero las diversas vías posibles incluyen la reducción de la inflamación, menos daño oxidativo, el control de la sensibilidad al sodio y la disminución de la rigidez arterial 48. Con respecto a los efectos adversos, sólo se encontró 1 evento adverso grave (accidente cerebrovascular) en 386 participantes. Acerca de, Church et al 49 informaron en un ECA de 221 individuos con diferentes rutinas de entrenamiento, 5 eventos cardiovasculares ninguno relacionado con el ejercicio físico. A pesar de ello, se debe tener en cuenta que se han reportado mayores efectos adversos en adultos diabéticos mayores en estudios previos 50. Esto puede explicarse por la fragilidad y mayor prevalencia de comorbilidades en esta población. Por lo tanto, los resultados deben considerarse con precaución ya que las edades medias de los ensayos estuvieron entre 60 y 70 años. Teniendo en cuenta que la diabetes es uno de los principales problemas de salud pública 51, nuestro estudio muestra que una medida de bajo costo y relativamente fácil de implementar como el ejercicio aeróbico ayuda en gran medida a los componentes del síndrome metabólico en la población mayor. Su implantación en el sistema sanitario, como un programa dedicado a la actividad aeróbica, potencialmente podría reducir significativamente la aparición de complicaciones, evitar el avance a corto plazo a un evento cardiovascular con mayor mortalidad con un alto riesgo de secuelas irreversibles y una mayor dependencia. Además, se pueden agregar los efectos beneficiosos indirectos que reducen en gran medida la fragilidad de este grupo de edad, sin embargo, debido a que los outcome estudias son subrogados, no se puede confirmar la relevancia clínica. Por último, y no menos importante, probablemente ayudaría a reducir la dosis de fármacos hipoglucemiantes e hipotensores, lo que podría traducirse en un menor coste en el mantenimiento de las enfermedades crónicas. Del mismo modo, nuestra relevancia radica en que, hasta donde sabemos, se trata de la primera revisión sistemática que analiza los efectos del ejercicio aeróbico sobre los componentes del síndrome metabólico en la población anteriormente mencionada, lo que ayudaría a orientar el manejo futuro e implementar este tipo de ejercicio en la práctica diaria de estos pacientes. Limitaciones Nuestra investigación tuvo algunas limitaciones. En primer lugar, hubo un alto porcentaje de estudios con riesgo alto o moderado de sesgo. En segundo lugar, las características de las intervenciones fueron heterogéneas, sin embargo, se realizó un análisis de subgrupos según el tiempo de intervención, la supervisión y la intensidad, que la mayoría no mostró diferencias, estos resultados deben considerarse con precaución debido al bajo número de ensayos. En tercer lugar, este estudio abarcó siete ECA, la mayoría de los cuales tuvieron un número relativamente bajo de participantes, aunque se realizó un análisis sensible excluyendo cada estudio, que no mostró diferencias. Y cuarto, no fue posible evaluar el efecto específico de diferentes rutinas de ejercicio aeróbico porque en todos los ECA incluidos la intervención fue la misma (cinta de correr o caminar), pero se debe considerar que este tipo de entrenamiento es el más utilizado en el grupo de edad estudiado. CONCLUSIONES Entre los ensayos clínicos disponibles, que estudiaron el efecto del ejercicio aeróbico sobre los componentes del síndrome metabólico en adultos mayores con diagnóstico de DT2 en comparación con los controles sin ejercicio, encontramos una disminución en los valores de glucosa en ayunas, triglicéridos glicosilados de hemoglobina, PAS, PAD y una pequeña modificación de triglicéridos y HDL. Sin embargo, estos resultados deben ser interpretados con cautela debido a la baja relevancia clínica. A su vez, en la mayoría de los ensayos clínicos, los eventos adversos no se informaron durante las intervenciones, o fueron muy aislados, lo que dificultó su asociación con él. Por último, se recomienda realizar ensayos clínicos de mejor calidad metodológica. multicéntrico y con muestras más grandes para que pueda dar una correcta representación de los efectos del ejercicio aeróbico. RECONOCIMIENTOS Conflicto de interés Todos los autores han declarado que no hay conflicto de intereses para esta revisión sistemática. Contribuciones de Autores Mercedes Miranda y Joshua Ramírez realizaron las búsquedas en la base de datos, el análisis de datos y la interpretación de los resultados. Miguel Cabanillas realizó todos los análisis estadísticos de datos. Mercedes Miranda y Joshua Ramírez fueron los responsables de la preparación del manuscrito. Isabel Pinedo y José Luis Paz asesoraron durante la interpretación de datos y redacción de manuscritos. Todos los autores participaron en la concepción, el diseño y la interpretación de los datos. Todos los autores revisaron el manuscrito y aprobaron la versión final para su envío. Rol del patrocinador No hubo patrocinadores involucrados en el diseño del estudio, los métodos, el reclutamiento de sujetos, la recopilación de datos, el análisis o la preparación de este documento. REFERENCIAS 1. United Nations. Department of Economic and Social Affairs Population. World Population Ageing 2019 [Internet]. 2020. Available from: https://www.un.org/en/development/desa/population/publications/pdf/ageing /WorldPopulationAgeing2019-Highlights.pdf 2. Internation Diabetes Federation. Atlas de la Diabetes de la FID 2019. 7th ed. 2019;144. Available from: http://www.idf.org/sites/default/files/Atlas-poster- 2014_ES.pdf 3. Centers for Disease Control and Prevention and The Merck Company Foundation. 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Modest Changes in High-Density Lipoprotein Concentration and Metabolism With Prolonged Exercise Training. Circulation. 1988;78(1):25–34. 42. Pan B, Ge L, Xun Y qin, Chen Y jing, Gao C yun, Han X, et al. Exercise training modalities in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis. Int J Behav Nutr Phys Act. 2018;15(1):1–14. 43. Gao S, Tang J, Yi G, Li Z, Chen Z. The Therapeutic Effects of Mild to Moderate Intensity Aerobic Exercise on Glycemic Control in Patients with Type 2 Diabetes Mellitus : A Meta-Analysis of Randomized Trials. Diabetes Ther [Internet]. 2021;12(10):2767–81. Available from: https://link.springer.com/article/10.1007%2Fs13300-021-01149-0 44. Muscella A, Stef E. The Regulation of Fat Metabolism during Aerobic Exercise. 2021; 45. Schwingshackl L, Missbach B, Dias S, König J, Hoffmann G. 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Effect of All- Extremity High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Aerobic Fitness in Middle-Aged and Older Adults with Type 2 Diabetes: A Randomized Controlled Trial. Exp Gerontol. 2019;116:46–53. 51. Al-lawati JA. Diabetes Mellitus: A Local and Global Public Health Emergency! 2017;32(3):177–9. ANEXOS Anexo 1. Estrategia de búsqueda electrónica Databases Search strategy Pubmed/ Medline #1 (“Diabetes mellitus”[MeSH] OR “Diabetes Mellitus Type 2”[tiab] OR “Diabetes Mellitus Noninsulin-Dependent”[tiab] OR “Diabetes Mellitus Non Insulin Dependent”[tiab] OR “Diabetes Mellitus Non- Insulin-Dependent”[tiab] OR “Non-Insulin-Dependent Diabetes Mellitus”[tiab] OR “Diabetes Mellitus Stable”[tiab] OR “Diabetes Mellitus Type II”[tiab] OR “NIDDM”[tiab] OR “Diabetes Mellitus Noninsulin Dependent”[tiab] OR “Diabetes Mellitus Slow- Onset”[tiab] OR “Type 2 Diabetes”[tiab]) #2 (“exercise”[MeSH] OR “Exercises”[tiab] OR “Physical Activity”[tiab] OR “Activities, physical”[tiab] OR “activity, physical”[tiab] OR “physical activities”[tiab] OR “Exercise Physical”[tiab] OR “Exercises, physical”[tiab] OR “Physical Exercise”[tiab] OR “physical exercises”[tiab] OR “Aerobic Exercise”[tiab] OR “Aerobic Exercises”[tiab] OR “Exercises Aerobic”[tiab] OR “Exercise Training”[tiab] OR “Exercise Trainings”[tiab] OR “Training Exercise”[tiab] OR “Aerobic training”[tiab] OR "endurance training"[MeSH] OR “Training Endurance”[tiab] OR “Physical endurance”[tiab] OR "sports"[MeSH] OR “Sport”[tiab] OR “Athletic*”[tiab] OR "walking"[MeSH] OR “Ambulation”[tiab] OR "running"[MeSH] OR “Runnings”[tiab] OR “Swimming”[tiab] OR “Treadmill”[tiab] OR “Treadmill Test”[tiab] OR “Treadmill Tests”[tiab] OR “Jogging”[MeSH]) #3 ("Randomized Controlled Trial"[PT] or "Randomized Controlled Trials as Topic"[Mesh] OR "Clinical Trial"[PT] OR "Clinical Trials as Topic"[Mesh] OR "Clinical Trial, Phase III"[PT] OR "Clinical Trial, Phase II"[PT] OR "Double-Blind Method"[Mesh] OR "Random Allocation"[Mesh] OR "Single-Blind Method"[Mesh] OR (random*[tiab]) OR ((randomized[tiab] OR randomised[tiab] OR clinical[tiab] OR control*[tiab]) AND trial[tiab]) OR ((singl*[tiab] OR doubl*[tiab] OR trebl*[tiab] OR tripl*[tiab]) AND (blind*[tiab] OR mask*[tiab])) OR (“Placebos”[Mesh] OR placebo*[tiab]) OR ("Cross- Over Studies"[Mesh]) OR ((crossover[tiab] OR cross-over[tiab] OR “cross over”[tiab]) AND (design*[tiab] OR study[tiab] OR studies[tiab] OR procedure*[tiab] OR trial*[tiab]))) #4 #1 AND #2 AND #3 Scopus #1 (TITLE-ABS-KEY("Exercise" OR "Exercises" OR "Aerobic training" OR "Physical Activity" OR "Physical Activities" OR "Physical Exercise" OR "Physical Exercises" OR "Aerobic Exercise" OR "Aerobic Exercises" OR "Exercise Training" OR "Exercise Trainings")) OR (TITLE-ABS- KEY("Endurance training" OR "Physical endurance")) OR (TITLE-ABS- KEY("Treadmill" OR "Treadmill Test" OR "Treadmill Tests")) OR (TITLE-ABS-KEY("Pools Swimming" OR "Swimming Pool")) OR (TITLE- ABS-KEY("Jogging")) OR (TITLE-ABS-KEY ("Sports" OR "Sport" OR "Athletics" OR "Athletic")) OR (TITLE-ABS-KEY("Walking" OR "Ambulation")) OR (TITLE-ABS-KEY("Running" OR "Runnings")) OR (TITLE-ABS-KEY("Jogging")) #2: TITLE-ABS-KEY ("Diabetes Mellitus Non Insulin Dependent" OR "Diabetes Mellitus Noninsulin Dependent" OR "Non Insulin Dependent Diabetes Mellitus" OR "Noninsulin Dependent Diabetes Mellitus" OR "Diabetes Mellitus Stable" OR "Stable Diabetes Mellitus" OR "NIDDM" OR "Diabetes Mellitus Slow Onset" OR "Slow Onset Diabetes Mellitus" OR "Type 2 Diabetes Mellitus" OR "Type 2 Diabetes" OR "Diabetes Mellitus Type 2" OR "Diabetes Type 2" OR "Diabetes Mellitus Type II" OR "Diabetes Type II" OR "Type II Diabetes Mellitus" OR "Type II Diabetes" OR "Diabetes mellitus 2" OR "Diabetes mellitus II") #3: ((TITLE-ABS-KEY ("randomized" OR "randomised" OR "clinical" OR "control*") AND TITLE-ABS-KEY ("trial")) OR (TITLE-ABS-KEY("singl*" OR "doubl*" OR "trebl*" OR "tripl*") AND TITLE-ABS-KEY("blind*" OR "mask*")) OR (TITLE-ABS-KEY("crossover" OR "cross-over" OR "cross over") AND TITLE-ABS-KEY("design*" OR "study" OR "studies" OR "procedure*" OR "trial*")) OR TITLE-ABS-KEY("Randomized Controlled Trial" OR "Randomized Controlled Trials as Topic" OR "Clinical Trial" OR "Clinical Trials as Topic" OR "Clinical Trial, Phase III" OR "Clinical Trial, Phase II" OR "Double-Blind Method" OR "Random Allocation" OR "Single-Blind Method" OR "random*" OR "placebo*")) #4 ( LIMIT-TO ( PUBYEAR,2021) OR LIMIT-TO ( PUBYEAR,2020) OR LIMIT-TO ( PUBYEAR,2019) OR LIMIT-TO ( PUBYEAR,2018) OR LIMIT- TO ( PUBYEAR,2017) OR LIMIT-TO ( PUBYEAR,2016) OR LIMIT-TO ( PUBYEAR,2015) OR LIMIT-TO ( PUBYEAR,2014) OR LIMIT-TO ( PUBYEAR,2013) OR LIMIT-TO ( PUBYEAR,2012) OR LIMIT-TO ( PUBYEAR,2011) OR LIMIT-TO ( PUBYEAR,2010) ) #5 ( LIMIT-TO ( DOCTYPE,"ar" ) ) #6: #1 AND #2 AND #3 AND #4 AND 5 Web of #1: TS=("Exercise" OR "Exercises" OR "Aerobic training" OR "Physical science Exercise" OR "Physical Exercises" OR "Aerobic Exercise" OR "Aerobic Exercises" OR "Exercise Training" OR "Exercise Trainings" OR "Endurance training" OR "Physical endurance" OR "Treadmill" OR "Treadmill Test" OR "Treadmill Tests" OR "Pools Swimming" OR "Swimming Pool" OR "Jogging" OR "Sports" OR "Sport" OR "Athletics" OR "Athletic" OR "Walking" OR "Ambulation" OR "Running" OR "Runnings") #2: TS=("Diabetes Mellitus Non Insulin Dependent" OR "Diabetes Mellitus Noninsulin Dependent" OR "Non Insulin Dependent Diabetes Mellitus" OR "Noninsulin Dependent Diabetes Mellitus" OR "Diabetes Mellitus Stable" OR "Stable Diabetes Mellitus" OR "NIDDM" OR "Diabetes Mellitus Slow Onset" OR "Slow Onset Diabetes Mellitus" OR "Type 2 Diabetes Mellitus" OR "Type 2 Diabetes" OR "Diabetes Mellitus Type 2" OR "Diabetes Type 2" OR "Diabetes Mellitus Type II" OR "Diabetes Type II" OR "Type II Diabetes Mellitus" OR "Type II Diabetes" OR "Diabetes mellitus 2" OR "Diabetes mellitus II") #3: TS=(randomized OR randomised OR clinical OR control*) AND TS=(trial) #4: TS=(singl* OR doubl* OR trebl* OR tripl*) AND TS=(blind* OR mask*)) #5: TS=(crossover OR cross-over OR "cross over") AND TS=(design* OR study OR studies OR procedure* OR trial*) #6: TS=("Randomized Controlled Trial" OR "Randomized Controlled Trials as Topic" OR "Clinical Trial" OR "Clinical Trials as Topic" OR "Clinical Trial, Phase III" OR "Clinical Trial, Phase II" OR "Double-Blind Method" OR "Random Allocation" OR "Single-Blind Method" OR random* OR placebo*) #7: #3 OR #4 OR #5 OR #6 #8: #1 AND #2 AND #7 Cochrane #1 MeSH descriptor: [Exercise] explode all trees #2 (“Exercises“ OR “Physical Activity” OR “Activities Physical” OR “Activity Physical” OR “Physical Activities” OR “Exercise Physical” OR “Exercises Physical” OR “Physical Exercise” OR “Physical Exercises” OR “Exercise Aerobic” OR “Aerobic Exercise” OR “Aerobic Exercises” OR “Exercises Aerobic” OR “Exercise Training” OR “Exercise Trainings” OR “Training Exercise” OR “Trainings Exercise” OR “Aerobic training”):ti,ab,kw #3 MeSH descriptor: [Endurance Training] explode all trees #4 (“Training Endurance” OR “Phyisical endurance”):ti,ab,kw #5 MeSH descriptor: [Sports] explode all trees #6 (sport OR athletics OR athletic):ti,ab,kw #7 MeSH descriptor: [Swimming] explode all trees #8 (swimming):ti,ab,kw #9 MeSH descriptor: [Walking] explode all trees #10 (ambulation):ti,ab,kw #11 MeSH descriptor: [Running] explode all trees #12 (runnings):ti,ab,kw #13 ("treadmill" OR "treadmill test" OR "test, treadmill" OR "treadmill tests" OR "jogging"):ti,ab,kw #14 MeSH descriptor: [Diabetes Mellitus, Type 2] explode all trees #15 (“Diabetes Mellitus, Type 2” OR “Diabetes Mellitus, Noninsulin- Dependent” OR “Diabetes Mellitus, Non Insulin Dependent” OR “Diabetes Mellitus, Non-Insulin-Dependent” OR “Non-Insulin- Dependent Diabetes Mellitus” OR “Diabetes Mellitus, Stable” OR “Stable Diabetes Mellitus” OR “Diabetes Mellitus, Type II” OR “NIDDM” OR “Diabetes Mellitus, Noninsulin Dependent” OR “Diabetes Mellitus, Slow-Onset” OR “Diabetes Mellitus, Slow Onset” OR “Slow-Onset Diabetes Mellitus” OR “Type 2 Diabetes Mellitus” OR “Noninsulin-Dependent Diabetes Mellitus” OR “Noninsulin Dependent Diabetes Mellitus” OR “Type 2 Diabetes” OR “Diabetes, Type 2”):ti,ab,kw #16 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13) AND (#14 OR #15) #17 ("Randomized Controlled Trial" OR "Clinical Trial" OR "Clinical Trial, Phase III" OR "Clinical Trial, Phase II"):pt #18 MeSH descriptor: [Randomized Controlled Trials as Topic] explode all trees #19 MeSH descriptor: [Clinical Trials as Topic] explode all trees #20 MeSH descriptor: [Double-Blind Method] explode all trees #21 MeSH descriptor: [Random Allocation] explode all trees #22 MeSH descriptor: [Random Allocation] explode all trees #23 MeSH descriptor: [Placebos] explode all trees #24 MeSH descriptor: [Cross-Over Studies] explode all trees #25 (random* OR placebo*):ti,ab,kw #26 (((randomized OR randomised OR clinical OR control*) AND trial)):ti,ab,kw #27 (((singl* OR doubl* OR trebl* OR tripl*) AND (blind* OR mask*))):ti,ab,kw #28 (((crossover OR cross-over OR “cross over”) AND (design* OR study OR studies OR procedure* OR trial*))):ti,ab,kw #29 #16 AND (#17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28) Google (“Exercise” OR “Ejercicio” OR “aerobic training” OR “ejercicio Scholar aeróbico” OR “Sport” OR “Deporte” OR “Walking” OR “caminata OR “running” OR “carrera”) AND (“Diabetes mellitus type 2” OR “Type 2 diabetes”) Anexo 2. Lista de estudios excluidos después de la revisión del texto completo FIRST CITE AUTHOR TITLE YEAR REASON FOR EXCLUSION The Effect of the Transtheoretical Model Based Walking Exercise 1 Serin Training and Follow-Up on Improving Exercise Behavior and 2020 not elderly patients Metabolic Control in Patients with Type 2 Diabetes Neuromusculoskeletal disorders in patients with type 2 diabetes 2 Adeniyi mellitus: Outcome of a twelve-week therapeutic exercise 2010 not elderly patients programme Metabolic changes following a 1-year diet and exercise 3 Albu 2010 not elderly patients intervention in patients with type 2 diabetes Anti-inflammatory effect of exercise training in subjects with 4 Balducci type 2 diabetes and the metabolic syndrome is dependent on 2010 not elderly patients exercise modalities and independent of weight loss Effect of T'ai Chi exercise on biochemical profiles and oxidative 5 Chen 2010 not elderly patients stress indicators in obese patients with type 2 diabetes Effects of nordic walking and exercise in type 2 diabetes mellitus: 6 Gram 2010 not elderly patients A randomized controlled trial Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients 7 Kadoglou 2010 not elderly patients with type 2 diabetes The effects of total energy expenditure from all levels of physical activity vs. physical activity energy expenditure from moderate- 8 Koo 2010 not elderly patients to-vigorous activity on visceral fat and insulin sensitivity in obese Type 2 diabetic women Effect of exercise training on physical fitness in type II diabetes 9 Larose 2010 not elderly patients mellitus Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by 10 Meex 2010 without control group increased myocellular fat storage and improved insulin sensitivity Supervised walking groups to increase physical activity in type 2 11 Negri 2010 not elderly patients diabetic patients Effects of aerobic exercise, resistance exercise or both, on 12 Reid patient-reported health status and well-being in type 2 diabetes 2010 not elderly patients mellitus: A randomised trial Long- but not short-term multifactorial intervention with focus 13 Sixt on exercise training improves coronary endothelial dysfunction 2010 not elderly patients in diabetes mellitus type 2 and coronary artery disease Improved pancreatic β-cell function in type 2 diabetic patients 14 Solomon after lifestyle-induced weight loss is related to glucose- 2010 without control group dependent insulinotropic polypeptide The effect of aerobic exercise on glycosylated hemoglobin values 15 Yavari 2010 not elderly patients in type 2 diabetes patients Diet or diet plus physical activity versus usual care in patients 16 Andrews with newly diagnosed type 2 diabetes: the Early ACTID 2011 not elderly patients randomised controlled trial The effect of a supported exercise programme in patients with 17 Backx 2011 not elderly patients newly diagnosed Type 2 diabetes: a pilot study Effects of exercise on glycosylated hemoglobin type 2 diabetic 18 Barragan 2011 not available patients from the West of Mexico Effects of aerobic exercise and whole body vibration on 19 Behboudi 2011 not elderly patients glycaemia control in type 2 diabetic males Effects of aerobic exercise on selected physiological parameters 20 Bello 2011 not elderly patients and quality of life in patients with type 2 diabetes mellitus [Benefits of a home-based physical exercise program in elderly 21 Ferrer 2011 not intervention subjects with type 2 diabetes mellitus] Application of an Exercise Intervention on the Evolution of 22 Hare Diastolic Dysfunction in Patients With Diabetes Mellitus Efficacy 2011 not elderly patients and Effectiveness Exercise attenuates the premature cardiovascular aging effects 23 Huebschmann 2011 not clinical trial of type 2 diabetes mellitus The effects of aerobic, resistance, and combined exercise on 24 Jorge metabolic control, inflammatory markers, adipocytokines, and 2011 not elderly patients muscle insulin signaling in patients with type 2 diabetes mellitus Effect of Chronic Regular Exercise on Serum Ischemia-Modified 25 Kurban 2011 not elderly patients Albumin Levels and Oxidative Stress in Type 2 Diabetes Mellitus Associations between physical fitness and HbA(1c) in type 2 26 Larose 2011 not elderly patients diabetes mellitus Aerobic and resistance training effects compared to aerobic 27 Lucotti 2011 not elderly patients training alone in obese type 2 diabetic patients on diet treatment Training increases peroxiredoxin 2 contents in the erythrocytes 28 Moghaddam 2011 not elderly patients of overweight/obese men suffering from type 2 diabetes Improvement of quality of life with supervised exercise training 29 Nicolucci 2011 not clinical trial in subjects with type 2 diabetes mellitus Design and methods for a pilot randomized clinical trial involving 30 Schneider exercise and behavioral activation to treat comorbid type 2 2011 not elderly patients diabetes and major depressive disorder Lifestyle change diminishes a hypertensive response to exercise 31 Schultz 2011 not elderly patients in type 2 diabetes Immediate and long-term effects of addition of exercise to a 16- 32 Snel week very low calorie diet on low-grade inflammation in obese, 2011 not elderly patients insulin-dependent type 2 diabetic patients Exercise Training Fails to Reduce Blood Pressure in Type 2 33 Stewart 2011 not clinical trial Diabetes: A Randomized Controlled Trial Stewart Regular physical exercise training assists in preventing type 2 34 Teixeira diabetes development: focus on its antioxidant and anti- 2011 not clinical trial inflammatory properties SKELETAL MUSCLE AND SUBCUTANEOUS ADIPOSE TISSUE ADAPTATIONS TO POWER TRAINING IN OLDER ADULTS WITH 35 Wang 2011 not available TYPE 2 DIABETES: A DOUBLE BLIND, RANDOMIZED SHAM- EXERCISE CONTROLLED TRIAL Efecto del ejercicio físico en el control metabólico y en factores 36 Aguila de riesgo de pacientes con diabetes mellitus tipo 2: estudio cuasi 2012 not elderly patients experimental Effects of Tai Chi Exercise on glucose control, neuropathy scores, 37 Ahn balance, and quality of life in patients with type 2 diabetes and 2012 not elderly patients neuropathy Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of body weight loss in 38 Balducci 2012 not elderly patients subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES) A randomized trial of exercise for blood pressure reduction in 39 Barone type 2 diabetes: effect on flow-mediated dilation and circulating 2012 not elderly patients biomarkers of endothelial function Effects of exercise on sRAGE levels and cardiometabolic risk 40 Choi factors in patients with type 2 diabetes: a randomized controlled 2012 not elderly patients trial Sedentary time, breaks in sedentary time and metabolic 41 Cooper 2012 not elderly patients variables in people with newly diagnosed type 2 diabetes The effect of different training programs on antioxidant status, 42 de Oliveira 2012 not elderly patients oxidative stress, and metabolic control in type 2 diabetes Effect of exercise on blood pressure in type 2 diabetes: a 43 Dobrosielski 2012 not elderly patients randomized controlled trial Impact of lifestyle intervention and metformin on health-related 44 Florez 2012 not elderly patients quality of life: the diabetes prevention program randomized trial A randomised trial of a weight loss intervention for overweight 45 Gallagher and obese people diagnosed with coronary heart disease and/or 2012 not elderly patients type 2 diabetes Acute high‐intensity interval exercise reduces the postprandial 46 Gillen glucose response and prevalence of hyperglycaemia in patients 2012 no outcome with type 2 diabetes Effects of eccentric and concentric exercises on some blood 47 Hajihasani, 2012 not elderly patients biochemical parameters in patients with type 2 diabetes Lower physical activity is a strong predictor of cardiovascular 48 Lijima 2012 not clinical trial events in elderly patients with type 2 diabetes mellitus beyond traditional risk factors: the Japanese Elderly Diabetes Intervention Trial Effects of aerobic exercise intensity on abdominal and thigh 49 Jung adipose tissue and skeletal muscle attenuation in overweight 2012 not elderly patients women with type 2 diabetes mellitus The impact of aerobic exercise training on novel adipokines, 50 Kadoglou 2012 not elderly patients apelin and ghrelin, in patients with type 2 diabetes The effects and physiological mechanisms of free-living interval- 51 Karstoft walking training on glycaemic control in type 2 diabetes patients: 2012 not elderly patients a randomised, controlled trial Intermittent exercise with and without hypoxia improves insulin 52 Mackenzie 2012 not elderly patients sensitivity in individuals with type 2 diabetes 53 Marquez El ejercicio en el tratamiento de la diabetes mellitus tipo 2 2012 not clinical trial Impact of an exercise intervention on DNA methylation in 54 Nitert skeletal muscle from first-degree relatives of patients with type 2012 not elderly patients 2 diabetes Promoting physical activity in sedentary elderly Malays with type 55 Sazlina 2012 not clinical trial 2 diabetes: a protocol for randomised controlled trial Prolonged exercise training increases intramuscular lipid content 56 Shaw and perilipin 2 expression in type I muscle fibers of patients with 2012 without control group type 2 diabetes Preliminary findings in the heart rate variability and 57 Simmonds haemorheology response to varied frequency and duration of 2012 without control group walking in women 65-74 yr with type 2 diabetes Effects of adding exercise to a 16-week very low-calorie diet in 58 Snel 2012 not elderly patients obese, insulin-dependent type 2 diabetes mellitus patients Quality of life in type 2 diabetes mellitus after a very low calorie 59 Snel 2012 no outcome diet and exercise Effect of exercise training modality on C-reactive protein in type 60 Swift 2012 not elderly patients 2 diabetes The effect of exercise training modality on serum brain derived 61 Swift 2012 not elderly patients neurotrophic factor levels in individuals with type 2 diabetes Regular physical exercise as a strategy to improve antioxidant 62 Teixeira and anti-inflammatory status: benefits in type 2 diabetes 2012 not clinical trial mellitus Testing the effectiveness of a self-efficacy based exercise van der 63 intervention for inactive people with type 2 diabetes mellitus: 2012 not elderly patients Heijden design of a controlled clinical trial Both resistance- and endurance-type exercise reduce the prevalence of hyperglycaemia in individuals with impaired 64 Van dijk 2012 not intervention glucose tolerance and in insulin-treated and non-insulin-treated type 2 diabetic patients EFFECT OF AEROBIC EXERCISE, RESISTANCE TRAINING OR COMBINED TRAINING ON GLYCAEMIC CONTROL AND 65 Yavari 2012 not elderly patients CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH TYPE 2 DIABETES Impact of moderate versus mild aerobic exercise training on 66 Abd inflammatory cytokines in obese type 2 diabetic patients: a 2013 not elderly patients randomized clinical trial Time course of improvement of metabolic parameters after a 12 67 Adeniyi week physical exercise programme in patients with type 2 2013 not elderly patients diabetes: the influence of gender in a Nigerian population Influence of 3 months endurance training on red cell 68 Ahmad deformability in non insulin dependent type 2 diabetes mellitus 2013 not elderly patients patients Changes in physical activity and modelled cardiovascular risk 69 Barakat following diagnosis of diabetes: 1-year results from the 2013 not elderly patients ADDITION-Cambridge trial cohort Impact of Reinforcement of Diabetes Self-Care on Poorly 70 Beverly 2013 not elderly patients Controlled Diabetes A Randomized Controlled Trial The influence of physical activity on vascular complications and 71 Blomster 2013 no outcome mortality in patients with type 2 diabetes mellitus Early management of type 2 diabetes based on a SMBG strategy: 72 de la Torre 2013 not elderly patients the way to diabetes regression-the St Carlos study Effect of exercise on abdominal fat loss in men and women with 73 Dobrosielski 2013 not elderly patients and without type 2 diabetes Intensive weight loss intervention in older individuals: results 74 Espeland from the Action for Health in Diabetes Type 2 diabetes mellitus 2013 not intervention trial The effects of an exercise and lifestyle intervention program on 75 Fiocco cardiovascular, metabolic factors and cognitive performance in 2013 not elderly patients middle-aged adults with type ii diabetes: A pilot study A randomized comparison of a commercially available portion- 76 Foster controlled weight-loss intervention with a diabetes self- 2013 not elderly patients management education program Effects of Nordic walking on cardiovascular risk factors in 77 Fritz overweight individuals with type 2 diabetes, impaired or normal 2013 not elderly patients glucose tolerance Early management of type 2 diabetes based on a SMBG strategy: The way to diabetes regression - The St Carlos study: A 3-year, 78 de la Torre 2013 not elderly patients prospective, randomized, clinic-based, interventional study with parallel groups Four-year change in cardiorespiratory fitness and influence on 79 Jakicic glycemic control in adults with type 2 diabetes in a randomized 2013 not elderly patients trial: the Look AHEAD Trial Determinants of the Changes in Glycemic Control with Exercise 80 Johannsen 2013 not elderly patients Training in Type 2 Diabetes: A Randomized Trial The Effects of Free-Living Interval Walking Training on Glycemic 81 Karstoft Control, Body Composition, and Physical Fitness in Type 2 2013 not elderly patients Diabetic Patients A randomized, controlled trial The effect of Tai Chi on health-related quality of life in people 82 Liu with elevated blood glucose or diabetes: A randomized 2013 not elderly patients controlled trial Changes in insulin resistance and HbA1c are related to exercise- 83 Mavros mediated changes in body composition in older adults with type 2013 not intervention 2 diabetes: interim outcomes from the GREAT2DO trial Effects of exercise training on arterial function in type 2 diabetes 84 Montero 2013 not clinical trial mellitus Weight-bearing versus nonweight-bearing exercise for persons 85 Mueller with diabetes and peripheral neuropathy: A randomized 2013 not elderly patients controlled trial A culturally adapted lifestyle intervention addressing a Middle Eastern immigrant population at risk of diabetes, the MEDIM 86 Saha 2013 not clinical trial (impact of Migration and Ethnicity on Diabetes In Malmö): study protocol for a randomized controlled trial Changes in body fat distribution and fitness are associated with 87 Senechal changes in hemoglobin A1c after 9 months of exercise training: 2013 not elderly patients results from the HART-D study The influence of hyperglycemia on the therapeutic effect of 88 Solomon exercise on glycemic control in patients with type 2 diabetes 2013 not elderly patients mellitus Exercise improves quality of life in indigenous Polynesian 89 Sukala 2013 not elderly patients peoples with type 2 diabetes and visceral obesity Feasibility and preliminary efficacy of high intensity interval 90 Terada 2013 without control group training in type 2 diabetes Exploring the variability in acute glycemic responses to exercise 91 Terada 2013 without control group in type 2 diabetes Effects of a 12-week aerobic training on glycemic control in type 92 Tomar 2013 not elderly patients 2 diabetes mellitus male patients Endurance exercise alters cellular immune status and resistin 93 Wenning concentrations in men suffering from non-insulin-dependent 2013 not elderly patients type 2 diabetes Effect of Aerobic Exercise Training on MDA and TNF- α Levels in 94 Arslan 2014 not elderly patients Patients with Type 2 Diabetes Mellitus Movement as Medicine for Type 2 Diabetes: protocol for an open pilot study and external pilot clustered randomised controlled 95 Avery trial to assess acceptability, feasibility and fidelity of a 2014 not clinical trial multifaceted behavioural intervention targeting physical activity in primary care 96 Balducci Physical exercise as therapy for type 2 diabetes mellitus 2014 not clinical trial The Effect of a Long-Term, Community-Based Exercise Program 97 Bello on Bone Mineral Density in Postmenopausal Women with Pre- 2014 not elderly patients Diabetes and Type 2 Diabetes The INSPIRED study: A randomised controlled trial of the Whole 98 Clarke Person Model of disease self-management for people with type 2014 not elderly patients 2 diabetes Association between objectively assessed sedentary time and 99 Cooper physical activity with metabolic risk factors among people with 2014 not elderly patients recently diagnosed type 2 diabetes Step Monitoring to improve ARTERial health (SMARTER) through 100 Dasgupta step count prescription in type 2 diabetes and hypertension: Trial 2014 not clinical trial design and methods Positive effects of football on fitness, lipid profile, and insulin 101 de sousa 2014 not elderly patients resistance in Brazilian patients with type 2 diabetes Aerobic and strength training in concomitant metabolic 102 Earnest 2014 not elderly patients syndrome and type 2 diabetes Long-term impact of behavioral weight loss intervention on 103 Espeland 2014 not elderly patients cognitive function Sedentary time and markers of inflammation in people with 104 Falconer 2014 not elderly patients newly diagnosed type 2 diabetes Changes in adipose tissue depots and metabolic markers 105 Gallagher following a 1-year diet and exercise intervention in overweight 2014 not elderly patients and obese patients with type 2 diabetes Effect of improved fitness beyond weight loss on cardiovascular 106 Gibbs risk factors in individuals with type 2 diabetes in the Look AHEAD 2014 not elderly patients study Multiple behaviour change intervention and outcomes in 107 Griffin recently diagnosed type 2 diabetes: the ADDITION-Plus 2014 not elderly patients randomised controlled trial Effect of progressive pedometer based walking intervention on 108 Guglani quality of life and general well being among patients with type 2 2014 not elderly patients diabetes High-intensity interval exercise effectively improves cardiac 109 Hollekim function in patients with type 2 diabetes mellitus and diastolic 2014 not elderly patients dysfunction: a randomized controlled trial Impact of leisure-time physical activity on glycemic control and 110 Kaizu cardiovascular risk factors in Japanese patients with type 2 2014 not elderly patients diabetes mellitus: The Fukuoka Diabetes Registry Effect of different training mode on Interleukin-6 (IL-6) and C- 111 Kim reactive protein (CRP) in type 2 diabetes mellitus (T2DM) 2014 not elderly patients patients The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for 112 Krause 2014 not elderly patients oxidative stress, low-grade inflammation and nitric oxide production The Effects of 12 Weeks Regular Aerobic Exercise on Brain- 113 Lee derived Neurotrophic Factor and Inflammatory Factors in 2014 not elderly patients Juvenile Obesity and Type 2 Diabetes Mellitus A standard ballroom and Latin dance program to improve fitness 114 Mangeri and adherence to physical activity in individuals with type 2 2014 not elderly patients diabetes and in obesity Near-Normalization of Glycemic Control in Patients with Type 2 Diabetes with a Glucagon-like Peptide-1 Receptor Agonist in 115 Mensberg 2014 without control group Combination with Exercise Training: A Randomized, Double- Blinded, Placebo-Controlled Clinical Trial Continuous vs interval training on glycemic control and macro- 116 Mitranum 2014 not elderly patients and microvascular reactivity in type 2 diabetic patients Exercise improves gait, reaction time and postural stability in 117 Morrison 2014 not elderly patients older adults with type 2 diabetes and neuropathy A comparison of the effects of aerobic and intense exercise on 118 Phillips the type 2 diabetes mellitus risk marker adipokines, adiponectin 2014 not clinical trial and retinol binding protein-4 A six-month exercise intervention in subclinical diabetic heart 119 Sacre disease: effects on exercise capacity, autonomic and myocardial 2014 not elderly patients function Exercise increases cutaneous nerve density in diabetic patients 120 Singleton 2014 not elderly patients without neuropathy 121 Subramanian Physio ball exercises on obesity and type II diabetes 2014 not available Effects of Physioball exercises on glycemic control and quality life 122 Subramanian 2014 not elderly patients of Type II diabetic patients Effect of diet or diet plus physical activity versus usual care on inflammatory markers in patients with newly diagnosed type 2 123 Thompson 2014 not elderly patients diabetes: the Early ACTivity in Diabetes (ACTID) randomized, controlled trial Effect of Aerobic Training on Glucose Control and Blood Pressure 124 Yan 2014 not elderly patients in T2DDM East African Males Remission of Recently Diagnosed Type 2 Diabetes Mellitus With 125 Ades 2015 not elderly patients Weight Loss and Exercise A lifestyle program of exercise and weight loss is effective in 126 Ades preventing and treating type 2 diabetes mellitus: why are 2015 not clinical trial programs not more available? Bone metabolism and hand grip strength response to aerobic 127 Al Shreef versus resistance exercise training in non-insulin dependent 2015 not elderly patients diabetic patients Volume-dependent effect of supervised exercise training on 128 Balducci fatty liver and visceral adiposity index in subjects with type 2 2015 not elderly patients diabetes The Italian Diabetes Exercise Study (IDES) Body weight dynamics following intentional weight loss and 129 Beavers physical performance: the Look AHEAD Movement and Memory 2015 not elderly patients Study Effects of exercise training on HbA1c and VO2peak in patients 130 Byrkjeland with type 2 diabetes and coronary artery disease: A randomised 2015 not elderly patients clinical trial Exercise excess pressure and exercise-induced albuminuria in 131 Climie 2015 not elderly patients patients with type 2 diabetes mellitus Impact of the activation of intention to perform physical activity 132 da Silva 2015 not elderly patients in type II diabetics: a randomized clinical trial Influence of Exercise on Leptin, Adiponectin and Quality of Life 133 Dede 2015 not elderly patients in Type 2 Diabetics Effects of Aerobic Exercise Based upon Heart Rate at Aerobic 134 Emerenziani 2015 not elderly patients Threshold in Obese Elderly Subjects with Type 2 Diabetes Effect of Elliptical High Intensity Interval Training on Metabolic 135 Fex 2015 not elderly patients Risk Factor in Pre- and Type 2 Diabetes Patients: A Pilot Study 136 Green Cardiovascular control during exercise in type 2 diabetes mellitus 2015 not clinical trial Daily physical activity assessed by a triaxial accelerometer is beneficially associated with waist circumference, serum 137 Hamasaki 2015 not elderly patients triglycerides, and insulin resistance in Japanese patients with prediabetes or untreated early type 2 diabetes Heterogeneous responses of personalised high intensity interval 138 Higgins training on type 2 diabetes mellitus and cardiovascular disease 2015 not elderly patients risk in young healthy adults Increase in Daily Steps After an Exercise Specialist Led Lifestyle 139 Johnson Intervention for Adults With Type 2 Diabetes In Primary Care: A 2015 not elderly patients Controlled Implementation Trial Comparison of the effects of Korean mindfulness-based stress 140 Jung 2015 not elderly patients reduction, walking, and patient education in diabetes mellitus Improved insulin sensitivity after exercise training is linked to 141 Kasumov 2015 not elderly patients reduced plasma C14:0 ceramide in obesity and type 2 diabetes Safety of aerobic exercise in people with diabetic peripheral 142 Kluding 2015 not elderly patients neuropathy: single-group clinical trial An investigation and comparison of the effectiveness of different 143 Lee exercise programmes in improving glucose metabolism and 2015 not elderly patients pancreatic β cell function of type 2 diabetes patients The effect of rebound exercise and treadmill walking on the 144 Maharaj quality of life for patients with non-insulin-dependent type 2 2015 not elderly patients diabetes Effect of a long-term regular physical activity on hypertension 145 Mobasseri 2015 not elderly patients and body mass index in type 2 diabetes patients Effects of 12 months exercise intervention on adipose tissue expression of chemokines in patients with type 2 diabetes and 146 Njerve 2015 not elderly patients stable coronary artery disease: a substudy of a randomized controlled trial (RCT) 147 Nylen Enhanced fitness and renal function in Type 2 diabetes 2015 not elderly patients Impact of a brief intervention on self-regulation, self-efficacy and 148 Olson 2015 not elderly patients physical activity in older adults with type 2 diabetes Effects of high intensity interval training versus moderate 149 Poblete intensity continuous training on the reduction of oxidative stress 2015 not elderly patients in type 2 diabetic adult patients: CAT Influence of physical activity and gender on arterial function in 150 Ring 2015 not elderly patients type 2 diabetes, normal and impaired glucose tolerance Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in 151 Senechal 2015 not elderly patients Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study Positive effects of Nordic Walking on anthropometric and 152 Sentinelli 2015 not elderly patients metabolic variables in women with type 2 diabetes mellitus Aerobic and resistance training do not influence plasma 153 Stegen 2015 not elderly patients carnosinase content or activity in type 2 diabetes Resistance to the beneficial effects of exercise in type 2 diabetes: 154 Stephens 2015 not elderly patients are some individuals programmed to fail? [Endurance training and walking improve blood glucose 155 Steurer 2015 not available metabolism in type 2 diabetes mellitus] 156 Subramanian Aerobic exercises on type II diabetic with hypertension 2015 not elderly patients Adoption and maintenance of gym-based strength training in the 157 Teychenne community setting in adults with excess weight or type 2 2015 not elderly patients diabetes: a randomized controlled trial Brain-derived neurotrophic factor correlated with muscle 158 Tsai strength in subjects undergoing stationary bicycle exercise 2015 not elderly patients training Cellular fibronectin response to supervised moderate aerobic 159 Alghadir 2016 not elderly patients training in patients with type 2 diabetes Effectiveness of a Lifestyle Intervention in Patients with Type 2 160 Assad Diabetes: The Physical Activity and Nutrition for Diabetes in 2016 not elderly patients Alberta (PANDA) Trial The role of vitamin D, obesity and physical exercise in regulation 161 Bener 2016 not elderly patients of glycemia in Type 2 Diabetes Mellitus patients Feasibility study of portable technology for weight loss and 162 Bentley 2016 not elderly patients HbA1c control in type 2 diabetes High intensity intermittent exercise improves cardiac structure 163 Cassidy and function and reduces liver fat in patients with type 2 2016 not elderly patients diabetes: a randomised controlled trial Glycemic load, exercise, and monitoring blood glucose (GEM): A 164 Cox 2016 not elderly patients paradigm shift in the treatment of type 2 diabetes mellitus Supervised group-exercise therapy versus home-based exercise 165 Dadgostar therapy: Their effects on Quality of Life and cardiovascular risk 2016 not elderly patients factors in women with type 2 diabetes Acute effect of fast walking on postprandial blood glucose 166 Deguchi 2016 not elderly patients control in type 2 diabetes Glucose control can be similarly improved after aquatic or dry- 167 Delevatti land aerobic training in patients with type 2 diabetes: A 2016 not elderly patients randomized clinical trial Glycemic reductions following water- and land-based exercise in 168 Delevatti 2016 not elderly patients patients with type 2 diabetes mellitus Effect of an intensive metabolic control lifestyle intervention in 169 Gamiochipi 2016 not elderly patients type-2 diabetes patients Exercise Training Normalizes Timing of Left Ventricular Untwist 170 Hollekim Rate, but Not Peak Untwist Rate, in Individuals with Type 2 2016 not elderly patients Diabetes and Diastolic Dysfunction: A Pilot Study High-intensity interval training reduces abdominal fat mass in 171 Maillard 2016 without control group postmenopausal women with type 2 diabetes Investigation of Plasma Visfatin Changes in Women with Type 2 Diabetes followed by Endurance, Resistance and Combined 172 Mehdizadeh 2016 not elderly patients Exercise: The Role of Lipid Profile, Glycemic Indices and Insulin Resistance Exercise Therapy for Management of Type 2 Diabetes Mellitus: 173 Miyauchi 2016 not elderly patients Superior Efficacy of Activity Monitors over Pedometers The effect of regular aerobic exercise on plasma levels of 25- 174 Moosavi hydroxy Vitamin D and insulin resistance in hypertensive 2016 not available postmenopausal women with type 2 diabetes Changes in some of the indicators of liver inflammation and 175 Mousavian cardiovascular risk factors during a term of synthetic aerobic 2016 not elderly patients exercise of diabetic women The Effect of Exercise with or Without Metformin on Glucose 176 Myette 2016 not elderly patients Profiles in Type 2 Diabetes: A Pilot Study SIX MONTHS EXERCISE INTERVENTION SIGNIFICANTLY 177 Picone IMPROVES ALBUMIN-CREATININE RATIO IN PATIENTS WITH 2016 not intervention TYPE 2 DIABETES: A RANDOMISED CONTROLLED TRIAL Can Time Efficient Exercise Improve Cardiometabolic Risk 178 Revdal 2016 not elderly patients Factors in Type 2 Diabetes? A Pilot Study A comparative study on the effect of endurance and resistance 179 Sobhanipour 2016 not elderly patients training on angiogenesis factors in elderly diabetic patients Does exercise training impact clock genes in patients with 180 Steidle 2016 not elderly patients coronary artery disease and type 2 diabetes mellitus? Targeting specific interstitial glycemic parameters with high- 181 Terada intensity interval exercise and fasted-state exercise in type 2 2016 not elderly patients diabetes Improvement of insulin sensitivity in response to exercise 182 Wagner training in type 2 diabetes mellitus is associated with vascular 2016 not elderly patients endothelial growth factor A expression The Effect of 12 Weeks Aerobic, Resistance, and Combined 183 AminiLari Exercises on Omentin-1 Levels and Insulin Resistance among 2017 not elderly patients Type 2 Diabetic Middle-Aged Women Exercise individualized by TRIMPi method reduces arterial 184 Bellia stiffness in early onset type 2 diabetic patients: A randomized 2017 not elderly patients controlled trial with aerobic interval training Procoagulant activity in patients with combined type 2 diabetes 185 Bratseth and coronary artery disease: No effects of long-term exercise 2017 not elderly patients training Reduced endothelial activation after exercise is associated with 186 Byrkjeland improved HbA(1c) in patients with type 2 diabetes and coronary 2017 not elderly patients artery disease Effect of a Community Health Worker Intervention Among 187 Carrasquillo Latinos With Poorly Controlled Type 2 Diabetes: The Miami 2017 not elderly patients Healthy Heart Initiative Randomized Clinical Trial Physician step prescription and monitoring to improve ARTERial 188 Dasgupta health (SMARTER): A randomized controlled trial in patients with 2017 not elderly patients type 2 diabetes and hypertension A pilot study of a Community Health Agent-led type 2 diabetes Do valle self-management program using Motivational Interviewing- 189 2017 not elderly patients Nascimento based approaches in a public primary care center in São Paulo, Brazil Effects of aerobic exercise on functional capacity, 190 dos anjos anthropometric measurements and inflammatory markers in 2017 without control group diabetic elderly women Effects of Physical Activity Intervention on Physical and Cognitive 191 Espeland 2017 not elderly patients Function in Sedentary Adults With and Without Diabetes Combined Interval Training and Post-exercise Nutrition in Type 2 192 Francois 2017 not elderly patients Diabetes: A Randomized Control Trial The impact of acute high-intensity interval exercise on 193 Francois 2017 not elderly patients biomarkers of cardiovascular health in type 2 diabetes Changes in skeletal muscle and organ size after a weight-loss 194 Gallagher 2017 not elderly patients intervention in overweight and obese type 2 diabetic patients Improving Self-Management of Type 2 Diabetes in Overweight and Inactive Patients Through an Educational and Motivational 195 Galle 2017 not elderly patients Intervention Addressing Diet and Physical Activity: A Prospective Study in Naples, South Italy The effect of care intervention for obese patients with type II 196 Jiang 2017 not elderly patients diabetes Effects of Supervised Structured Aerobic Exercise Training 197 Karimi Program on Interleukin-6, Nitric Oxide Synthase-1, and 2017 not elderly patients Cyclooxygenase-2 in Type 2 Diabetes Mellitus Optimization of aerobic exercise protocols in diabetes mellitus: 198 Kaur 2017 not elderly patients A randomized trial Effect of square aerobic exercise on cardiovascular risk factors 199 Liu and health-related quality of life in Chinese women with type 2 2017 not elderly patients diabetes Exercise intensity, redox homeostasis and inflammation in type 200 Mallard 2017 not elderly patients 2 diabetes mellitus Supervised vs. self-selected physical activity for individuals with 201 Mazzuca 2017 not elderly patients diabetes and obesity: the Lifestyle Gym program The effects of chronic aerobic exercise on cardiovascular risk 202 Miele 2017 not clinical trial factors in persons with diabetes mellitus Non-locomotive physical activity intervention using a tri-axial 203 Miyamoto 2017 not elderly patients accelerometer reduces sedentary time in type 2 diabetes Effect of regular exercise training on changes in HbA1c, BMI and 204 Najafipour VO(2)max among patients with type 2 diabetes mellitus: an 8- 2017 not elderly patients year trial Long-term effects of daily postprandial physical activity on blood 205 Nygaard 2017 not elderly patients glucose: a randomized controlled trial Impact of post-meal and one-time daily exercise in patient with 206 Pahra 2017 not elderly patients type 2 diabetes mellitus: a randomized crossover study The Impact of Burst Exercise on Cardiometabolic Status of 207 Pandey 2017 not elderly patients Patients Newly Diagnosed With Type 2 Diabetes Effects of supervised structured aerobic exercise training 208 Shakil program on high and low density lipoprotein in patients with 2017 not elderly patients type II diabetes mellitus Effects of supervised structured aerobic exercise training program on fasting blood glucose level, plasma insulin level, 209 Shakil 2017 not elderly patients glycemic control, and insulin resistance in type 2 diabetes mellitus High-intensity aerobic interval training improves aerobic fitness 210 Stoa 2017 not elderly patients and HbA1c among persons diagnosed with type 2 diabetes The Relative Efficacy of Land-Based and Water-Based Exercise 211 Suntraluck Training on Macro- and Microvascular Functions in Older 2017 without control group Patients With Type 2 Diabetes Cardiometabolic risk factors in type 2 diabetes with high fat and 212 Terada 2017 not elderly patients low muscle mass: At baseline and in response to exercise Effects of supervised structured aerobic exercise training 213 Rehman programme on level of Exertion, dyspnoea, VO2 max and Body 2017 not elderly patients Mass Index in patients with type 2 diabetes mellitus Short- and long-term effects of a need-supportive physical 214 Vanroy activity intervention among patients with type 2 diabetes 2017 not elderly patients mellitus: A randomized controlled pilot trial Walking with Diabetes (WW-DIAB) programme a walking 215 Arovah programme for Indonesian type 2 diabetes mellitus patients: A 2018 not elderly patients pilot randomised controlled trial Diets along with interval training regimes improves 216 Zadeh inflammatory & anti-inflammatory condition in obesity with type 2018 not elderly patients 2 diabetes subjects Effects of aerobic or resistance exercise training on 217 Bellavere cardiovascular autonomic function of subjects with type 2 2018 not elderly patients diabetes: A pilot study Multicomponent Exercise Improves Hemodynamic Parameters and Mobility, but Not Maximal Walking Speed, Transfer 218 Junior 2018 not elderly patients Capacity, and Executive Function of Older Type II Diabetic Patients Reducing sitting time versus adding exercise: differential effects 219 Duvivier 2018 not elderly patients on biomarkers of endothelial dysfunction and metabolic risk Evaluating the clinical implementation of structured exercise: A 220 Faroqi randomized controlled trial among non-insulin dependent type 2018 not elderly patients II diabetics Cardiovascular benefits of combined interval training and post- 221 Francois 2018 not elderly patients exercise nutrition in type 2 diabetes Effect of aerobic training on nerve conduction in men with type 222 Gholami 2 diabetes and peripheral neuropathy: A randomized controlled 2018 not elderly patients trial High-intensity interval training is more effective than moderate- intensity continuous training in reducing abdominal fat mass in 223 Maillard 2018 not intervention postmenopausal women with type 2 diabetes: A randomized crossover study Assessment of lower extremity muscle mass, muscle strength, 224 Nomura 2018 not clinical trial and exercise therapy in elderly patients with diabetes mellitus Influence of a mini-trampoline rebound exercise program on 225 Nuhu insulin resistance, lipid profile and central obesity in individuals 2018 not elderly patients with type 2 diabetes A 20-week exercise program improves markers of cognitive, 226 Pisabarro 2018 not elderly patients inflammatory and metabolic status in type 2 diabetic patients Quality of life and sleep quality are similarly improved after 227 Delevatti aquatic or dry-land aerobic training in patients with type 2 2018 not elderly patients diabetes: A randomized clinical trial Study protocol: a randomised controlled trial of supervised 228 Ranasinghe resistance training versus aerobic training in Sri Lankan adults 2018 not clinical trial with type 2 diabetes mellitus: SL-DART study The effect of 12 weeks of aerobic training on serum levels high sensitivity C-reactive protein, tumor necrosis factor-alpha, lipid 229 Saghebjoo 2018 not elderly patients profile and anthropometric characteristics in middle-age women patients with type 2 diabetes Response to a Supervised Structured Aerobic Exercise Training 230 Ur Program in Patients with Type 2 Diabetes Mellitus - Does Gender 2018 not elderly patients Make a Difference? A Randomized Controlled Clinical Trial Results From a Feasibility Study of Square-Stepping Exercise in 231 Shellington Older AdultsWith Type 2 Diabetes and Self-Reported Cognitive 2018 no outcome Complaints to Improve Global Cognitive Functioning COST-EFFECTIVE EXERCISE PROGRAMS ON HEALTH-STATUS OF 232 Faria MALAYSIAN DIABETIC INDIVIDUALS - A SOCIO-PSYCHOLOGICAL 2018 not elderly patients ANALYSIS A dose-response study of aerobic training for oxygen uptake, oxidative stress and cardiac autonomic function in type 2 233 Verma 2018 not elderly patients diabetes mellitus: study protocol for a randomized controlled trial The effect on glycaemic control of low-volume high-intensity 234 Winding interval training versus endurance training in individuals with 2018 not elderly patients type 2 diabetes Acute blood glucose, cardiovascular and exaggerated responses 235 Wormgoor to HIIT and moderate-intensity continuous training in men with 2018 not elderly patients type 2 diabetes mellitus Effect of high intensity interval training on heart rate variability 236 Ahmed and aerobic capacity in obese adults with type 2 Diabetes 2019 not elderly patients Mellitus Efficacy of high intensity interval training on endothelial function 237 Ahmed 2019 not available in diabetics with peripheral arterial insufficiency Effect of a multifactorial intervention on the increase in physical 238 Dominguez activity in subjects with type 2 diabetes mellitus: a randomized 2019 not elderly patients clinical trial (EMID Study) Acute effect of healthy walking on arterial stiffness in patients 239 Dominguez with type 2 diabetes and differences by age and sex: a pre-post 2019 not elderly patients intervention study Effect of PPARγ agonist on aerobic exercise capacity in relation 240 Bastien to body fat distribution in men with type 2 diabetes mellitus and 2019 not elderly patients coronary artery disease: a 1-yr randomized study Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1-Year Intensive 241 Berger 2019 not elderly patients Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial Managing free-living hyperglycemia with exercise or interrupted 242 Blankenship 2019 not elderly patients sitting in type 2 diabetes Reduction in HbA1c with Exercise videogames among 243 Bock participants with elevated HbA1c: Secondary analysis of the Wii 2019 not elderly patients Heart Fitness trial Electrically assisted cycling for individuals with type 2 diabetes 244 Bourne 2019 not clinical trial mellitus: protocol for a pilot randomized controlled trial Low-energy diet and physical activity for the remission of type 2 245 Das 2019 not clinical trial diabetes: a paradigm shift An Intensive Lifestyle Intervention to Treat Type 2 Diabetes in 246 Davis the Republic of the Marshall Islands: Protocol for a Randomized 2019 not clinical trial Controlled Trial Biomarkers of insulin action during single soccer sessions before 247 de Sousa and after a 12-week training period in type 2 diabetes patients 2019 not elderly patients on a caloric-restricted diet Acute aerobic exercise induced irisin release in type 2 diabetic 248 Elrefaey 2019 not elderly patients patients: Randomized clinical trial STRONG-D: Strength training regimen for normal weight 249 Faroqi 2019 not clinical trial diabetics: Rationale and design Lifestyle practices and glycemic control among type 2 diabetic 250 Fatimathu 2019 not elderly patients patients in north kerala Rationale, design and study protocol of the randomised 251 Gulsin 2019 not clinical trial controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study) Protocol for a randomised controlled trial to evaluate the 252 Hale effectiveness of the diabetes community exercise and education 2019 not clinical trial programme (DCEP) for long-term management of diabetes Effects of face-to-face and online training on self-care of middle- 253 Ildarabadi aged and elderly people with type 2 diabetes: A comparative 2019 not elderly patients study Study protocol for a multicentre, controlled non-randomised 254 Kitic trial: benefits of exercise physiology services for type 2 diabetes 2019 not clinical trial (BEST) Exercise training to reduce cardiovascular risk in patients with 255 Krankel metabolic syndrome and type 2 diabetes mellitus: How does it 2019 not clinical trial work? Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older 256 Lucertini 2019 not clinical trial Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial Effects of combined training with different intensities on 257 Magalhaes vascular health in patients with type 2 diabetes: a 1-year 2019 not elderly patients randomized controlled trial High-Intensity Interval Training Versus Moderate-Intensity Continuous Training in Middle-Aged and Older Patients with 258 Mendes 2019 not elderly patients Type 2 Diabetes: A Randomized Controlled Crossover Trial of the Acute Effects of Treadmill Walking on Glycemic Control Skeletal muscle Nur77 and NOR1 insulin responsiveness is 259 Mey blunted in obesity and type 2 diabetes but improved after 2019 not elderly patients exercise training MULTIDISCIPLINARY LIFESTYLE MANAGEMENT APPROACH IN 260 Motkova 2019 not elderly patients PATIENTS WITH TYPE 2 DIABETES MELLITUS IN REAL CLINICAL PRACTICE. RESULTS OF APPLICATION "LIFE IS EASY" PROGRAMME IN RUSSIA Effects of Aerobic and Resistance Training on Circulating Micro- 261 Olioso 2019 not elderly patients RNA Expression Profile in Subjects With Type 2 Diabetes Benefits of 1-Year Lifestyle Modification Program on Exercise 262 Piche Capacity and Diastolic Function Among Coronary Artery Disease 2019 not elderly patients Men With and Without Type 2 Diabetes Randomized Controlled Trial of Physical Exercise in Diabetic 263 Stubbs Veterans With Length-Dependent Distal Symmetric 2019 not elderly patients Polyneuropathy High intensity interval training protects the heart during 264 Suryanegara increased metabolic demand in patients with type 2 diabetes: a 2019 not elderly patients randomised controlled trial Sports therapy and recreation exercise program in type 2 265 Szilagyi 2019 not elderly patients diabetes: randomized controlled trial, 3-month follow-up The effects of poco-poco dance on the executive functions of type 2 diabetes mellitus patients with mild cognitive impairment 266 Theresa 2019 not elderly patients achieved through improvements in neuronal functions and plasticity Prescribing high-intensity interval exercise by RPE in individuals 267 Viana 2019 not elderly patients with type 2 diabetes: metabolic and hemodynamic responses Health literacy and exercise-focused interventions on clinical 268 Wang measurements in Chinese diabetes patients: A cluster 2019 not elderly patients randomized controlled trial HIIT Improves Left Ventricular Exercise Response in Adults with 269 Wilson 2019 not elderly patients Type 2 Diabetes Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients 270 Zaidi 2019 not elderly patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial One-year caloric restriction and 12-week exercise training 271 Zurlo intervention in obese adults with type 2 diabetes: emphasis on 2019 not elderly patients metabolic control and resting metabolic rate Effects of interval training on cardio metabolic risk factors and 272 Arefirad nitric oxide in type 2 diabetes patients: a randomized controlled 2020 not elderly patients trial Significant Dose-Response between Exercise Adherence and 273 Benham 2020 not elderly patients Hemoglobin A1c Change 274 Borhade Diabetes mellitus and exercise 2020 not clinical trial Glycemic excursion minimization in the management of type 2 275 Cox diabetes: a novel intervention tested in a randomized clinical 2020 not elderly patients trial Feasibility of a 26-Week Exercise Program to Improve Brain 276 Furlano 2020 not elderly patients Health in Older Adults at Risk for Type 2 Diabetes: A Pilot Study Improved carotid intima-media thickness-induced high-intensity 277 Ghardashi interval training associated with decreased serum levels of Dkk- 2020 not elderly patients 1 and sclerostin in type 2 diabetes Cycle Training improves vascular function and neuropathic 278 Gholami symptoms in patients with type 2 diabetes and peripheral 2020 not elderly patients neuropathy: A randomized controlled trial Effectiveness of Yoga-based Exercise Program Compared to 279 Gupta Usual Care, in Improving HbA1c in Individuals with Type 2 2020 not elderly patients Diabetes: A Randomized Control Trial Effects of Yoga Versus Sham Yoga on Oxidative Stress, Glycemic 280 Hegde Status, and Anthropometry in Type 2 Diabetes Mellitus: A Single- 2020 not elderly patients Blinded Randomized Pilot Study Usefulness of Exercise for Home Blood Pressure Control in 281 Iwai People with Diabetes: A Study Protocol for a Crossover 2020 not clinical trial Randomized Controlled Trial The Effect of the Transtheoretical Model Based Walking Exercise 282 Kaplan Training and Follow-Up on Improving Exercise Behavior and 2020 not elderly patients Metabolic Control in Patients with Type 2 Diabetes Impact of a supervised multicomponent physical exercise 283 Leite 2020 no outcome program on cognitive functions in patients with type 2 diabetes Effects of fitness qigong and tai chi on middle-aged and elderly 284 Li 2020 not elderly patients patients with type 2 diabetes mellitus Acute and chronic effects of muscle power training on blood 285 Machado 2020 without control group pressure in elderly patients with type 2 diabetes mellitus Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized 286 ranasinghe 2020 not elderly patients controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS) Effect of Walking on Sand with Dietary Intervention in 287 Seyam OverweightType 2 DiabetesMellitusPatients: A Randomized 2020 not elderly patients Controlled Trial Higher levels of daily physical activity are associated with better 288 Sorensen skin microvascular function in type 2 diabetes—The Maastricht 2020 not elderly patients Study Impact of Exercise-Nutritional State Interactions in Patients with 289 Verboven 2020 without control group Type 2 Diabetes Study on the effect of lifestyle intervention on metabolic indexes 290 Wang 2020 without control group of rural patients with type 2 diabetes mellitus Low-cost exercise interventions improve long-term 291 Wasenius cardiometabolic health independently of a family history of type 2020 not elderly patients 2 diabetes: a randomized parallel group trial The effect of low-volume high-intensity interval training on 292 Way cardiovascular health outcomes in type 2 diabetes: A 2020 not elderly patients randomised controlled trial Health literacy and exercise interventions on clinical outcomes in 293 Wei Chinese patients with diabetes: a propensity score-matched 2020 not elderly patients comparison Influence of Changes in Sedentary Time on Outcomes of 294 Whipple Supervised Exercise Therapy in Individuals with Comorbid 2020 not elderly patients Peripheral Artery Disease and Type 2 Diabetes The impact of exercise on serum irisin, osteocalcin, and 295 Yang adiponectin levels and on glycolipid metabolism in patients with 2020 not elderly patients type 2 diabetes Cardiovascular and systemic determinants of exercise capacity in 296 Bilak 2020 not clinical trial people with type 2 diabetes mellitus Process- and Outcome-Based Financial Incentives to Improve 297 Bilger Self-Management and Glycemic Control in People with Type 2 2020 not elderly patients Diabetes in Singapore: A Randomized Controlled Trial One-year intensive lifestyle intervention and improvements in health-related quality of life and mental health in persons with 298 MacDonald 2020 not elderly patients type 2 diabetes: A secondary analysis of the U-TURN randomized controlled trial Anexo 3. Características de los estudios incluidos en la revisión sistemática (n=7). Analized Time of Exercise Study Country Design Main inclusion criteria Main exclusion criteria sample intervention Comparator Adverse effect Primary outcome Conclusion intervention size (I/C) (h/w; follow up) Nonstrenuous core Older than 65 years, T2D for History of angina, Treadmill and (exercise ball), Aerobic exercise can reverse Randomized at least 5 years, normal ECG, myocardial infarction, Change in Baroreflex Madden, 201026 Canada 19/20 cycle 3h/w; 12 weeks nonstrenuous No reported function impairments of the single-blind study normal treadmill maximal stroke, chronic function ergometer strength training (very arterial baroreflex function exercise stress test pulmonary disease light dumbbells) Older than 65 years with Participants with Diet control and the Randomized open- T2D, scored more than 24 habitual alcohol Walking Aerobic exercise increases daily Sung, 201230 Korea 22/18 2.5h/w; 24 weeks. Standard medical care No reported management of label study points on the Mini-Mental consumption or liver exercise activity and glucose metabolism complications State Examination disease History of angina, Intervention: Older than 65 years with myocardial infarction, Syncopal exercise ball, Attenuation of the Vasodepressive carotid sinus Randomized T2D for at least 5 years, stroke, chronic Treadmill, cycle response with Madden,201327 Canada 20/20 3h/w; 12 weeks nonstrenuous vasodepressive hypersensitivity is resistant to single-blind study normal ECG, sedentary at pulmonary disease, ergometer carotid sinus strength training response aerobic exercise the beginning of the study smoking in the last 5 massage: 1 years (5%) Incapacity to recognize, Intervention: not being sedentary, stroke: 1 (2%), Aerobic exercise is associated Randomized Aged between 65-80 years, Change in glycated Parra-Sánchez,201533 Spain history of retinopathy, 47/41 Walking 2h/w;12 weeks No exercise sprain: 1 (2%) with an improvement in single-blind study T2D hemoglobin advanced nephropathy, Control: glycosylated hemoglobin congestive heart failure stroke: 1 (2%) Older than 60 years, T2D for Randomized at least 1 year, lack of Absence of >2 sessions Walking and Change in metabolic Aerobic exercise improves Askari, 201828 Iran 54/54 1 h/w, 12 weeks Without detail No reported Open label study cognitive and movement in the training program jogging indices metabolic indices disabilities. Inability to participate Change in body in exercise, history of composition, blood Women with T2D between Aerobic exercise improve in Randomized open- heart disease, blood Walking or Habitual physical glucose, lipid profile, Sijie Tan, 201829 China 6-10 years, aged between 16/15 3 h/w; 12 weeks No reported body composition, blood label study pressure greater than running activity levels serum adipokine 60-69 years glucose and insulin resistance 160/95 mmhg, and insulin pulmonary diseases, resistance Change in Aerobic exercise is effective on Aged between 60-70 years, History of dyslipidemia, antioxidant defense Randomized open- cardiometabolic risks, oxidative Hagag, 202034 Egypt BMI ranged between 25- hypertension, 20/20 Treadmill 2.25h/w; 12 weeks Standard medical care No reported and cardio- label study stress markers and antioxidant 34.9, T2D between 2-7 years complications of T2D metabolic risk status factors I: intervention, C: comparator, h: hours, w: week, T2D: type 2 diabetes, ECG: echocardiography Anexo 4. Riesgo de sesgo de los ECA incluidos según la herramienta Cochrane de riesgo de sesgo. Study Madden (2010) ! + + + + ! Sung (2012) - ! + + + - Madden (2013) + + + + + + Parra-Sanchez ! (2015) ! + + + ! Askari (2018) ! ! + + + ! Sijie (2018) ! + ! + + ! Hagag (2020) ! ! + + + ! ECA: ensayos controlados aleatorios Randomization process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported result Overall Anexo 5. análisis de sensibilidad Overall results Results after exclusion of each study Subgroup Excluded study SMD (95%CI) SMD (95% CI) Fasting glucose -1.76 [-2.78; -0.74] Madden(2010) -1.47 [-2.39; -0.47] Sung(2012) -1.96 [-3.33; -0.58] Madden(2013) -1.49 [-2.51; -0.47] Askari(2018) -2.11 [-3.09; -1.13] Sijie(2018) -1.82 [-3.09; -0.55] Triglycerides -0.34 [-0.67; -0.01] Sung(2012) -0.25 [-0.57; 0.08] Parra - Sanchez(2015) -0.44 [-0.71; -0.17] Askari(2018) -0.40 [-0.87; 0.07] Sijie(2018) -0.26 [-0.59; 0.07] Hagag(2020) -0.36 [-0.76; 0.05] HDL 0.41 [0.11; 0.72] Sung(2012) 0.39 [0.02; 0.77] Parra - Sanchez(2015) 0.59 [0.32; 0.86] Askari(2018) 0.24 [-0.03; 0.51] Sijie(2018) 0.44 [0.07; 0.80] Hagag(2020) 0.41 [0.03; 0.79] SBP -1.67 [-2.74; -0.61] Madden(2010) -1.41 [-2.55; -0.26] Madden(2013) -1.32 [-2.35; -0.29] Parra - Sanchez(2015) -2.08 [-3.19; -0.97] Hagag(2020) -1.91 [-3.49; -0.33] DBP -1.47 [-2.34; -0.60] Madden(2010) -1.50 [-2.68; -0.31] Madden(2013) -1.00 [-1.52; -0.48] Parra - Sanchez(2015) -1.80 [-2.79; -0.80] Hagag(2020) -1.62 [-2.87; -0.37] Glycated haemoglobin -0.63 [-0.87; -0.39] Sung(2012) -0.60 [-0.88; -0.32] Parra - Sanchez(2015) -0.78 [-1.08; -0.48] Askari(2018) -0.60 [-0.95; -0.26] Hagag(2020) -0.60 [-0.87; -0.32] SMD: standardized mean difference CI: confidence interval HDL: high density lipoprotein SBP: systolic blood pressure DBP: diastolic blood pressure Anexo 6. Análisis de subgrupos Test of relationship Test of heterogeneity Subgroup n SMD (95% CI) P value I² P-value Fasting glucose Intensity of exercise High or vigorous 2 -2.05 [-4.05; -0.06] 0.04 92% <0.01 Low or moderate 1 -1.57 [-2.39; -0.75] <0.01 No reported 2 -1.62 [-3.96; 0.72] 0.17 96% <0.01 Supervision of exercise Yes 3 -2.48 [-3.44; -1.53] <0.01 71% 0.03 No 2 -0.70 [-1.27; -0.12] 0.02 57% 0.13 Total Duration in hours >30 4 -2.11 [-3.09; -1.13] <0.01 82% <0.01 <30 1 -0.46 [-0.85; -0.08] 0.02 Triglycerides Intensity of exercise High or vigorous 1 -0.78 [-1.43; -0.13] 0.02 Low or moderate 2 -0.54 [-1.02; -0.07] 0.03 0% 0.37 No reported 2 -0.09 [-0.44; 0.26] 0.60 39% 0.20 Supervision of exercise Yes 3 -0.28 [-0.80; 0.23] 0.28 59% 0.09 No 2 -0.45 [-0.94; 0.03] 0.07 44% 0.18 Total Duration in hours >30 2 -0.79 [-1.28; -0.30] <0.01 0% 0.96 <30 3 -0.14 [-0.40; 0.13] 0.31 9% 0.33 HDL Intensity of exercise High or vigorous 1 0.52 [-0.12; 1.15] 0.11 Low or moderate 2 0.37 [-0.10; 0.84] 0.13 0% 0.71 No reported 2 0.41 [-0.29; 1.12] 0.25 85% 0.01 Supervision of exercise Yes 3 0.18 [-0.12; 0.48] 0.24 0% 0.56 No 2 0.70 [0.37; 1.03] <0.01 0% 0.5 Total Duration in hours >30 2 0.40 [-0.07; 0.88] 0.09 0% 0.60 <30 3 0.42 [-0.06; 0.90] 0.08 69% 0.04 Systolic blood preassure Intensity of exercise High or vigorous 1 -2.50 [-3.34; -1.65] <0.01 Low or moderate 1 -1.06 [-1.73; -0.39] <0.01 No reported 2 -1.63 [-3.79; 0.53] 0.14 95% <0.01 Supervision of exercise Yes 4 -1.67 [-2.24; -0.61] <0.01 90% <0.01 No 0 -- Total Duration in hours >30 2 -2.48 [-3.24; -2.01] <0.01 0% 0.66 ≤30 2 -0.74 [-1.20; -0.27] <0.01 36% 0.21 Dystolic Blood preassure Intensity of exercise High or vigorous 1 -1.47 [-2.18; -0.76] <0.01 No reported 2 -1.74 [-4.01; 0.53] 0.13 95% <0.01 Low or moderate 1 -1.11 [-1.78; -0.44] <0.01 Supervision of exercise Yes 4 -1.47 [-2.34; -0.60] <0.01 86% <0.01 No 0 Total Duration in hours >30 2 -2.17 [-3.61; -0.74] <0.01 84% 0.01 <30 2 -0.79 [-1.25; -0.33] <0.01 34% 0.22 Glycated haemoglobin Intensity of exercise High or vigorous 1 -0.85 [-1.50; -0.20] 0.01 Low or moderate 1 -0.86 [-1.52; -0.21] <0.01 No reported 2 -0.55 [-0.89; -0.20] <0.01 35% 0.22 Supervision of exercise Yes 2 -0.55 [-1.01; -0.08] 0.02 38% 0.20 No 2 -0.76 [-1.09; -0.42] <0.01 0% 0.74 Total Duration in hours >30 1 -0.85 [-1.50; -0.20] 0.01 <30 3 -0.60 [-0.88; -0.32] <0.01 13% 0.32 n: number of studies, SMD: standardized mean difference CI: confidence interval 1. The Intensity of exercise was defined 2. The study was considered supervised if Anexo 7. Lista de verificación de PRISMA Location Section and Item Checklist item where item is Topic # reported TITLE Title 1 Identify the report as a systematic review. Page 1 ABSTRACT Abstract 2 See the PRISMA 2020 for Abstracts checklist. Page 3 INTRODUCTION Rationale 3 Describe the rationale for the review in the context of existing Page 4 knowledge. Objectives 4 Provide an explicit statement of the objective(s) or question(s) the Page 4 review addresses. METHODS Eligibility 5 Specify the inclusion and exclusion criteria for the review and how Page 5 criteria studies were grouped for the syntheses. Location Section and Item Checklist item where item is Topic # reported Information 6 Specify all databases, registers, websites, organisations, reference lists Page 6 sources and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. Search 7 Present the full search strategies for all databases, registers and Supplementary strategy websites, including any filters and limits used. Material 1 Selection 8 Specify the methods used to decide whether a study met the inclusion Page 6 process criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. Data 9 Specify the methods used to collect data from reports, including how Page 6 collection many reviewers collected data from each report, whether they worked process independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. Data items 10a List and define all outcomes for which data were sought. Specify Page 6 whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect. 10b List and define all other variables for which data were sought (e.g. Page 5 participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. Study risk of 11 Specify the methods used to assess risk of bias in the included studies, Page 7 bias including details of the tool(s) used, how many reviewers assessed assessment each study and whether they worked independently, and if applicable, details of automation tools used in the process. Location Section and Item Checklist item where item is Topic # reported Effect 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean Pages 7 - 8 measures difference) used in the synthesis or presentation of results. Synthesis 13a Describe the processes used to decide which studies were eligible for Page 6 methods each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). 13b Describe any methods required to prepare the data for presentation Page 7 or synthesis, such as handling of missing summary statistics, or data conversions. 13c Describe any methods used to tabulate or visually display results of Page 8 individual studies and syntheses. 13d Describe any methods used to synthesize results and provide a Page 8 rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used. 13e Describe any methods used to explore possible causes of Pages 7 - 8 heterogeneity among study results (e.g. subgroup analysis, meta- regression). 13f Describe any sensitivity analyses conducted to assess robustness of the Page 8 synthesized results. Reporting bias 14 Describe any methods used to assess risk of bias due to missing results Page 8 assessment in a synthesis (arising from reporting biases). Certainty 15 Describe any methods used to assess certainty (or confidence) in the Page 8 assessment body of evidence for an outcome. RESULTS Location Section and Item Checklist item where item is Topic # reported Study 16a Describe the results of the search and selection process, from the Figure 1 selection number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. 16b Cite studies that might appear to meet the inclusion criteria, but which Supplementary were excluded, and explain why they were excluded. Material 2 Study 17 Cite each included study and present its characteristics. Supplementary characteristics Material 3 Risk of bias in 18 Present assessments of risk of bias for each included study. Supplementary studies Material 4 Results of 19 For all outcomes, present, for each study: (a) summary statistics for Figure 2 - 4 individual each group (where appropriate) and (b) an effect estimate and its studies precision (e.g. confidence/credible interval), ideally using structured tables or plots. Results of 20a For each synthesis, briefly summarise the characteristics and risk of Page 9 syntheses bias among contributing studies. 20b Present results of all statistical syntheses conducted. If meta-analysis Pages 9 - 11 was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. 20c Present results of all investigations of possible causes of heterogeneity Pages 9 - 11 among study results. 20d Present results of all sensitivity analyses conducted to assess the Supplementary robustness of the synthesized results. Material 4 Reporting 21 Present assessments of risk of bias due to missing results (arising from Supplementary biases reporting biases) for each synthesis assessed. Material 4 Location Section and Item Checklist item where item is Topic # reported Certainty of 22 Present assessments of certainty (or confidence) in the body of Table 1 evidence evidence for each outcome assessed. DISCUSSION Discussion 23a Provide a general interpretation of the results in the context of other Pages 11 - 14 evidence. 23b Discuss any limitations of the evidence included in the review. Page 15 23c Discuss any limitations of the review processes used. Page 15 23d Discuss implications of the results for practice, policy, and future Page 15 research. OTHER INFORMATION Registration 24a Provide registration information for the review, including register Page 5 and protocol name and registration number, or state that the review was not registered. 24b Indicate where the review protocol can be accessed, or state that a Page 5 protocol was not prepared. 24c Describe and explain any amendments to information provided at Page 5 registration or in the protocol. Support 25 Describe sources of financial or non-financial support for the review, Page 16 and the role of the funders or sponsors in the review. Competing 26 Declare any competing interests of review authors. Page 16 interests Availability of 27 Report which of the following are publicly available and where they Supplementary data, code can be found: template data collection forms; data extracted from material 3 and other included studies; data used for all analyses; analytic code; any other materials materials used in the review. Anexo 8. Aprobación de Ética Anexo 9. Resolución directoral académica de carrera de aprobación del proyecto