title: Relationships between insulin resistance and frailty with body composition and testosterone in men undergoing androgen deprivation therapy for prostate cancer.
abstract: OBJECTIVE
  While androgen deprivation therapy (ADT) has been associated with insulin resistance and frailty, controlled prospective studies are lacking. We aimed to examine the relationships between insulin resistance and frailty with body composition and testosterone.
  
  
  METHODS
  Case-control prospective study.
  
  
  METHODS
  Sixty three men with non-metastatic prostate cancer newly commencing ADT (n=34) and age-matched prostate cancer controls (n=29) were recruited. The main outcomes were insulin resistance (HOMA2-IR), Fried's frailty score, body composition by dual x-ray absorptiometry and short physical performance battery (SPPB) measured at 0, 6 and 12months. A generalised linear model determined the mean adjusted difference (95% CI) between groups.
  
  
  RESULTS
  Compared with controls over 12months, men receiving ADT had reductions in mean total testosterone level (14.1-0.4nmol/L, P<0.001), mean adjusted gain in fat mass of 3530g (2012, 5047), P<0.02 and loss of lean mass of 1491g (181, 2801), P<0.02. Visceral fat was unchanged. HOMA2-IR in the ADT group increased 0.59 (0.24, 0.94), P=0.02, which was most related to the increase in fat mass (P=0.003), less to lean mass (P=0.09) or total testosterone (P=0.088). Frailty increased with ADT (P<0.0001), which was related to decreased testosterone (P=0.028), and less to fat mass (P=0.056) or lean mass (P=0.79). SPPB was unchanged.
  
  
  CONCLUSIONS
  ADT is associated with increased insulin resistance and frailty within 12months of commencement, independently of confounding effects of cancer or radiotherapy. Insulin resistance appears to be mediated by subcutaneous or peripheral sites of fat deposition. Prevention of fat gain is an important strategy to prevent adverse ADT-associated cardiometabolic risks.
authors.affiliation: Department of MedicineThe University of Melbourne, Austin Health, Heidelberg, Victoria, Australia Department of Endocrinology adac@unimelb.edu.au.
authors.forename: Ada S
authors.initials: AS
authors.lastname: Cheung
authors.affiliation: Department of MedicineThe University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hoermann
authors.affiliation: Department of MedicineThe University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dupuis
authors.affiliation: Department of Radiation Oncology Austin HealthHeidelberg, Victoria, Australia.
authors.forename: Daryl Lim
authors.initials: DL
authors.lastname: Joon
authors.affiliation: Department of MedicineThe University of Melbourne, Austin Health, Heidelberg, Victoria, Australia Department of Endocrinology.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of MedicineThe University of Melbourne, Austin Health, Heidelberg, Victoria, Australia Department of Endocrinology.
authors.forename: Mathis
authors.initials: M
authors.lastname: Grossmann
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects*; D016022:Case-Control Studies; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D013739:Testosterone