Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0–5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.
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