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Breast cancer is associated to impaired glucose/insulin homeostasis in premenopausal obese/overweight patients

2017; Impact Journals LLC; Volume: 8; Issue: 46 Linguagem: Inglês

10.18632/oncotarget.20399

1949-2553

Raúl M. Luque, Laura M. López‐Sánchez, Alicia Villa-Osaba, Isabel M. Luque, Ana L. Santos-Romero, Elena M. Yubero‐Serrano, María Cara-García, Marina Álvarez Benito, José López‐Miranda, Manuel D. Gahete, Justo P. Castaño,

Cancer, Lipids, and Metabolism

// Raúl M. Luque 1, 2, 3, 4, 5, *, # , Laura M. López-Sánchez 1, 2, 3, 4, 5, * , Alicia Villa-Osaba 1, 2, 3, 4, 5, * , Isabel M. Luque 1, 3 , Ana L. Santos-Romero 1, 4, 6 , Elena M. Yubero-Serrano 1, 4, 7 , María Cara-García 1, 4, 6 , Marina Álvarez-Benito 1, 4, 6 , José López-Miranda 1, 4, 7 , Manuel D. Gahete 1, 2, 3, 4, 5, # and Justo P. Castaño 1, 2, 3, 4, 5, # 1 Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain 2 Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain 3 Hospital Universitario Reina Sofia, Córdoba, Spain 4 CIBERobn, Córdoba, Spain 5 ceiA3, Córdoba, Spain 6 Mammary Gland Unit, Hospital Universitario Reina Sofía, Córdoba, Spain 7 Lipids and Atherosclerosis Unit, Hospital Universitario Reina Sofía, Córdoba, Spain * These authors contributed equally to this work # These authors co-directed the work and should be considered co-senior authors Correspondence to: Raúl M. Luque, email: raul.luque@uco.es Manuel D. Gahete, email: bc2gaorm@uco.es Justo P. Castaño, email: justo@uco.es Keywords: breast cancer, glucose, insulin, OGTT, obesity Received: June 27, 2017 Accepted: July 25, 2017 Published: August 23, 2017 ABSTRACT The association between breast cancer (BCa) presence and altered glucose/insulin metabolism is controversial likely due to an inaccurate insulin resistance (IR) assessment and inappropriate stratification of patients by body-mass index (BMI) and menopausal state. 148 women with suspect of sporadic BCa were stratified by BMI and menopause. Fasting levels of glucose, insulin, glycohemoglobin and selected IR-related and tumor-derived markers were measured. Glucose/insulin levels during OGTT were used to calculate insulin resistance/sensitivity indexes. Analysis of 77 BCa-bearing patients and 71 controls showed an association between BCa and IR as demonstrated by impaired glucose/insulin homeostasis (increased fasting- and OGTT-induced glucose levels) and deteriorated IR indexes, which was especially patent in premenopausal women. The association between BCa presence and IR was markedly influenced by BMI, being obese BCa patients significantly more insulin resistant than controls. BCa presence was associated to elevated levels of IR (glucose, triglycerides) and tumor-derived (VEGF) markers, especially in overweight/obese patients. BCa presence is associated to IR in overweight/obese premenopausal but not in premenopausal normal weight or postmenopausal women. Our data support a bidirectional relationship between dysregulated/imbalanced glucose/insulin metabolism and BCa, as tumor- and IR-markers are correlated with the impairment of glucose/insulin metabolism in overweight/obese premenopausal BCa patients.