EFFECT OF EXERCISE ON THE INSULIN/IGF-1 SYSTEM IN CANCER PATIENTS - IMPLICATIONS FOR CARDIOMETABOLIC HEALTH AND QUALITY OF LIFE IN BREAST CANCER SURVIVORS AND OLDER ADULTS

Breast Cancer (BC) is the most common female cancer worldwide, and the growing number of adults aged ≥ 65 is expected to increase the population of elderly Breast Cancer Survivors (BCS). However, the effect of tailored aerobic exercise and Mediterranean diet (MD) on overall Quality of Life (QoL) considering fatigue, cardiometabolic health, glucose homeostasis, and the tumor growth regulation, remain unclear. Moreover, the role of reserve of oxygen uptake (V̇O2R) and fatigability as determinant of free-living energy expenditure in older adults is still unknown. Since cancer history is associated with higher fatigability and poor physical functioning, especially in older adults, this Thesis aimed to: (i) investigated the effect of a Lifestyle Intervention (LI), combining supervised aerobic exercise and MD guidance, on a) QoL including cancer-related fatigue (study 1); b) free-living glycemic profile (study 2); and c) Insulin-Like Growth Factor 1 (IGF-1) modulation (study 3) along with cardiometabolic health (e.g., maximum oxygen uptake [V̇O2max], % of fat mass, and caloric intake) in BCS within the MoviS clinical trial; and (ii) to examine V̇O2R and perceived fatigability as determinants of Activity Energy Expenditure (AEE) in older adults from the ENGAGE project (study 4). Four different studies were conducted: studies 1-3 recruited and randomized BCS into Control (GC) and Intervention (IG) groups, while study 4 followed a cross-sectional design. Study 1 showed that LI improved QoL and cardiometabolic health (e.g., physical functioning and V̇O2max) in the short-term. However, benefits returned to the baseline in the long-term, emphasize the need for follow-up education to sustain healthy habits. MD guidance was insufficient to achieve optimal adherence, and age and Tamoxifen influencing QoL changes. Study 2 suggested that the LI improved free-living glycemic control (e.g., insulin level) more in the IG than in the CG. CG showed a worsening trend in time spent above glucose range (> 180 mg/dl). These effects were related to food intake between active and non-active days. Study 3 showed the baseline IGF-1 role in assessing LI efficacy: V̇O2max improvements were associated with an increase in IGF-1 in participants with low baseline levels and with a decrease in those with high levels. Study 4 found V̇O2R significantly correlated with fatigability and AEE, and V̇O2R, age and % of fat mass were predictors of AEE. Four functional profiles were detected confirming that fatigability was significantly different for women compared to men. Although fatigability was not a predictor of AEE, it was significantly associated to V̇O2R. This Thesis showed the complex interplay between self-reported outcomes (e.g., QoL and fatigability) and physiological component (e.g., V̇O2max, and IGF-1) in two different cohorts. Integrating these measures is essential to understand QoL and cardiometabolic health in order to prevent BC incidence favoring healthy ageing.