Since the cumulative incidence curves indicated a difference in breast cancer events considering the change in adiponectin between baseline and 12 months, in the multi-mediator analyses, we tested the hypothesis that both the biomarkers (each among leptin, IGF-I, IGFBP-1, glycemia, insulin, HOMA-IR index, hs-CRP, or SHBG) at baseline or their changes (log-transformed) and the 12-month adiponectin increase may mediate the effect of baseline BMI on breast cancer risk. The gene discussed is INS; the disease is breast carcinoma.