Di Sebastiano, KatiePinthus, JehonathanDuivenvoorden, WilhelminaPatterson, LaurelDubin, JoelMourtzakis, Marina2023-05-022023-05-022017-02https://doi.org/10.1002/pros.23262http://hdl.handle.net/10012/19398This is the peer reviewed version of the following article: Di Sebastiano, K. M., Pinthus, J. H., Duivenvoorden, W. C. M., Patterson, L., Dubin, J. A., &amp; Mourtzakis, M. (2016). Elevated C-peptides, abdominal obesity, and abnormal Adipokine profile are associated with higher Gleason scores in Prostate cancer. The Prostate, 77(2), 211–221, which has been published in final form at https://doi.org/10.1002/pros.23262. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Background: Prostate cancer development is associated with numerous lifestyle factors (i.e., physical activity, nutrition intake) and metabolic perturbations. These factors have been studied independently; here, we used an integrative approach to characterize these lifestyle and metabolic parameters in men undergoing diagnostic prostate biopsies. Methods: We prospectively evaluated 51 consecutive men for body composition, metabolic factors including glucose- and lipid-related measures, as well as lifestyle factors prior to prostate biopsy. Evaluations were performed in a blinded manner and were subsequently related to biopsy outcomes for: (i) presence or absence of cancer; and (ii) where cancer was present, Gleason score. Results: Serum C-peptide concentrations were significantly greater in participants with Gleason scores ≥4 + 3 (2.8 ± 1.1 ng/ml) compared to those with Gleason 3 + 3 (1.4 ± 0.6 ng/ml) or Gleason 3 + 4 (1.3 ± 0.8 ng/ml, P = 0.002), suggesting greater insulin secretion despite lack of differences in fasting glucose concentrations. Central adiposity, measured by waist circumference, was significantly greater in participants with Gleason ≥4 + 3 (110.1 ± 7.4 cm) compared to those with Gleason 3 + 4 (102.0 ± 9.5 cm, P = 0.028). Men with Gleason ≥4 + 3 also had significantly greater leptin concentrations than those with lower Gleason scores (Gleason ≥4 + 3: 15.6 ± 3.3 ng/ml vs. Gleason 3 + 4: 8.1 ± 8.1 ng/ml, P < 0.05) and leptin:adiponectin ratio (Gleason ≥4 + 3: 9.7 ± 6.1 AU, Gleason 3 + 4: 2.9 ± 3.2, Gleason 3 + 3: 2.4 ± 2.1 AU, P = 0.013). Conclusions: We profiled a cluster of obesity-related metabolic perturbations (C-peptide, central adiposity, leptin, and leptin:adiponectin ratios) which may associate with more aggressive prostate cancer histology.enprostate cancerobesityglucoseadipokinesinsulinwaist circumferencecentral obesityleptinadiponectinArticle