The influence of exercise intensity on insulin sensitivity and the insulin-like growth factor axis in colorectal cancer survivors

Abstract

Of all cancers, colorectal cancer has the fourth highest incidence rate worldwide and it is estimated that colorectal cancer is responsible for the deaths of approximately 608,000 people each year. Due to improved detection and treatment protocols, mortality from this disease has decreased in recent years, with 5-year survival rates for localised tumours approximately 90%. However, the risk of developing second primary colorectal cancers is higher in survivors, with an estimated 1.4 fold increased risk compared to healthy controls. Physical activity is significantly related to colorectal cancer risk; individuals who engage in higher levels of physical activity are at a 26% reduced risk of developing colorectal cancer compared to those who engage in lower levels of physical activity. Moreover, there is convincing epidemiological evidence to suggest that vigorous activity elicits a greater risk reduction for the development of colorectal cancer than activity performed at a moderate intensity. Previous research has implicated insulin sensitivity and the insulin-like growth factor (IGF) axis as factors related to the risk of colorectal cancer. The aim of this study was to investigate the influence of exercise intensity on insulin sensitivity and the IGF axis in colorectal cancer survivors. Twenty-nine men and women aged 33 – 82 years completed a 4-week randomised controlled exercise intervention incorporating three sessions per week of moderate intensity exercise (MIE) or high intensity interval training (HIE). For this trial, the MIE protocol was considered a ‘usual care’ control group in the context of physical activity recommendations, given that the exercise demands for those in the MIE group align with the current exercise oncology guidelines. Before and after the intervention, insulin sensitivity using an oral glucose tolerance test (OGTT), insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-III (IGFBP-III) were measured. Peak cardiorespiratory (VO2peak) test, fat mass, lean mass, and body fat percentage were also measured pre- and post-intervention. HIE significantly improved 120 min glucose readings from the ii OGTT following the 4-week intervention (-7.1%, p = 0.037). No significant (p > 0.05) between- or within-group changes were found for other measures of insulin sensitivity, IGF-I, or IGFBP-III. VO2peak significantly increased in both the HIE (+23.0%, p = 0.013) and MIE group (+1.7%, p = 0.025) with training, with no significant between-group differences (p = 0.124). In the HIE group only, significant changes were found for fat mass (-3.3%, p ≤ 0.001), lean mass (+1.8%, p ≤ 0.001), and body fat percentage (-3.3%, p ≤ 0.001) following the intervention. There were no significant (p > 0.05) changes in body composition for the MIE group. The absence of change in insulin sensitivity and the IGF axis following the exercise interventions are likely due to baseline values in these measures falling within ranges described in healthy persons. The significant training-induced changes in VO2peak, fat mass, lean mass, and body fat percentage observed in the HIE group are potentially clinically meaningful, as improvements in these markers have previously been associated with reduced cancer specific- and all cause- mortality. The present study has shown that HIE is a safe and effective mode of exercise for rapidly improving cardiorespiratory fitness and body composition, but not insulin sensitivity or the IGF axis, in colorectal cancer survivors.