Insulin resistance during androgen deprivation therapy in men with prostate cancer

Author:

Basaria Shehzad1ORCID,Taplin Mary‐Ellen2,McDonnell Marie1,Simonson Donald C.1,Lin Alexander P.3,Dufour Alyssa B.4,Habtemariam Daniel4,Nguyen Paul L.5,Ravi Praful2ORCID,Kibel Adam S.6,Sweeney Christopher J.7,D’Amico Anthony V.5,Roberts Daniel A.2,Xu Wenxin2,Wei Xiao X.2,Sunkara Rajitha2,Choudhury Atish D.2ORCID,Mantia Charlene2,Beltran Himisha2,Pomerantz Mark2ORCID,Berchuck Jacob E.2,Martin Neil E.5,Leeman Jonathan E.5ORCID,Mouw Kent W.5,Kilbridge Kerry E.2,Bearup Richelle1,Kackley Hannah1,Kafel Hussein1,Huang Grace1,Reid Kieran F.1,Storer Thomas1,Braga‐Basaria Milena1,Travison Thomas G.4

Affiliation:

1. Division of Endocrinology, Diabetes and Hypertension Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

2. Lank Center for Genitourinary Oncology and Dana‐Farber Cancer Institute Harvard Medical School Boston Massachusetts USA

3. Department of Radiology Center for Clinical Spectroscopy Brigham and Women's Hospital and Dana‐Farber Cancer Institute Harvard Medical School Boston Massachusetts USA

4. Hebrew Senior Life, and Department of Medicine Hinda and Arthur Marcus Institute for Aging Research Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA

5. Department of Radiation Oncology Brigham and Women's Hospital and Dana‐Farber Cancer Institute Harvard Medical School Boston Massachusetts USA

6. Division of Urology Department of Surgery Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

7. South Australian Immunogenomics Cancer Institute University of Adelaide Adelaide South Australia Australia

Abstract

AbstractBackgroundAndrogen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear.MethodsThe ADT & Metabolism Study was a single‐center, 24‐week, prospective observational study that enrolled ADT‐naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non‐ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks.ResultsAt 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], −2.10 to 4.43; p = .47) or skeletal muscle (−3.2; 95% CI, −7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non‐ADT group. Men undergoing ADT gained 3.7 kg of fat mass.ConclusionsIn men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short‐term ADT.

Publisher

Wiley

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