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Feasibility and Efficacy of Interval Walking in Patients With Colorectal Cancer

ABSTRACT: Background: The level physical exercise is strongly associated with colorectal cancer risk in the general population, and recent data shows that physical activity after a colorectal cancer diagnosis is inversely associated with mortality risk, indication the physical exercise can protect against disease progression. However, few studies have successfully performed exercise interventions in patients with colorectal cancer, and the potential mechanisms responsible for the tumor suppressing effects of exercise remain poorly explored. Purpose: To investigate interval-walking, delivered by the InterWalk smart phone application as exercise-modality in patients with colorectal cancer. Specifically it is the aim to explore if InterWalk is safe and feasible as well as effective to improve cardio-metabolic health profile. Subjects: Colorectal cancer patients, stage I-III, who are at least one month post-surgery and have concluded any adjuvant chemotherapy treatment, are eligible for inclusion. Exclusion criteria are: age <18; any major surgical procedure planned within 6 months after inclusion; pregnancy; ongoing treatment for any known malignancy; performance status > 1; unable to read and understand Danish Methods: 40 colorectal cancer patients are included and randomized to I) InterWalk or II) waiting list control for 24 weeks. Patients are evaluated at baseline, week 12 and week 24 by assessment measures to determine cardio-metabolic health profile and other relevant study outcomes, including: cardiopulmonary exercise test (VO2peak); anthropometrics; blood pressure; resting heart rate; body composition; health related quality of life questionnaires; plasma concentration levels of cholesterol, triglycerides, insulin, glucose and inflammatory cytokines; insulin sensitivity; and cognitive function.

DISEASE(S): Colon Cancer,Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2186867 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However, a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects. Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased. Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration. Insulin-treated T2DM subjects before and after 52 weeks of exercise training (T2DM_0 and T2DM_52), normoglycemic controls (NGT) and pre-diabetes subjects (IGT) and were selected. RNA was extracted from skeletal muscle biopsies and hybridized on Affymetrix microarrays.

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Feasibility and Efficacy of Interval Walking in Patients With Colorectal Cancer

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