Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear.
The 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.
At 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.
In 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.
Cancer. 2024 Jun 16 [Epub ahead of print]
Shehzad Basaria, Mary-Ellen Taplin, Marie McDonnell, Donald C Simonson, Alexander P Lin, Alyssa B Dufour, Daniel Habtemariam, Paul L Nguyen, Praful Ravi, Adam S Kibel, Christopher J Sweeney, Anthony V D'Amico, Daniel A Roberts, Wenxin Xu, Xiao X Wei, Rajitha Sunkara, Atish D Choudhury, Charlene Mantia, Himisha Beltran, Mark Pomerantz, Jacob E Berchuck, Neil E Martin, Jonathan E Leeman, Kent W Mouw, Kerry E Kilbridge, Richelle Bearup, Hannah Kackley, Hussein Kafel, Grace Huang, Kieran F Reid, Thomas Storer, Milena Braga-Basaria, Thomas G Travison
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lank Center for Genitourinary Oncology and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., Department of Radiology, Center for Clinical Spectroscopy, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., 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., Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., Division of Urology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, South Australia, Australia.