Journal Article

Gaining metabolic insight in older men undergoing androgen deprivation therapy for prostate cancer (the ADT & Metabolism Study): Protocol of a longitudinal, observational, cohort study

Habtemariam, Daniel, Dufour, Alyssa B., Lin, Alexander, Kafel, Hussein, Reid, Kieran, Storer, Thomas, Simonson, Donald C., Kibel, Adam S., Taplin, Mary-Ellen, Ravi, Praful, Travison, Thomas G., Kackley, Hannah, Nguyen, Paul L., Basaria, Shehzad, Bearup, Richelle, McDonnell, Marie, Braga-Basaria, Milena

2023

Overview

Androgen deprivation therapy (ADT), a cornerstone of treatment for patients with locally advanced and metastatic prostate cancer, is associated with many adverse effects, including osteoporosis, sexual dysfunction, fatigue, and vasomotor symptoms. It is also associated with loss of muscle mass and increased adiposity. This change in body composition is likely the inciting event in the development of insulin resistance, an independent risk factor for diabetes mellitus and cardiovascular disease. Although the occurrence of insulin resistance during ADT has been reported, it remains unclear whether this insulin resistance is primarily hepatic or muscular. Similarly, the mechanisms that lead to insulin resistance also remain unknown. The ADT & Metabolism Study was designed to address these knowledge gaps, as the elucidation of the predominant site of insulin resistance will allow prevention strategies and the use of targeted, tissue-specific insulin-sensitizing agents in patients undergoing ADT. This prospective, mechanistic, single-center, 24-week, observational cohort study will enroll treatment-naïve adult men with prostate cancer about to undergo surgical or medical ADT for at least 24 weeks (ADT group; n = 50) and a control group of men who had undergone radical prostatectomy and are in remission (non-ADT group, n = 25). The primary outcome is to determine the site of insulin resistance (skeletal muscle or liver) using frequent sampling oral glucose tolerance test at baseline and 12 and 24 weeks after commencement of ADT (ADT group) or after enrollment in the study (non-ADT group). Secondary outcomes will assess changes in hepatic and intramyocellular fat (using magnetic resonance spectroscopy), inflammatory markers, adipokines, free fatty acids, and changes in body composition (assessed using dual-energy x-ray absorptiometry) and their correlation with the development of insulin resistance. Exploratory outcomes will include changes in muscle performance, physical function, physical activity, vitality, and sexual drive.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipose tissue / Aged / Androgen Antagonists - adverse effects / Androgens / Antineoplastic Agents, Hormonal - therapeutic use / Biology and Life Sciences / Body composition / Cancer therapies / Cardiovascular disease / Cardiovascular diseases / Care and treatment / Cohort analysis / Cohort Studies / Cytokines / Deprivation / Diabetes / Diabetes mellitus / Dual energy X-ray absorptiometry / Enrollments / Evaluation / Fatty acids / Glucose / Glucose tolerance / Glucose tolerance tests / Health aspects / Health risks / Health services / Hemoglobin / Humans / Inflammation / Insulin / Insulin resistance / Insulin Resistance - physiology / Liver / Magnetic resonance / Magnetic resonance spectroscopy / Male / Medicine and Health Sciences / Metabolic syndrome / Metabolism / Metabolites / Metastases / Mortality / Muscles / Muscular fatigue / Musculoskeletal system / Observational studies / Observational Studies as Topic / Older people / Osteoporosis / Patient outcomes / Patients / Physical activity / Physical Sciences / Plasma / Prospective Studies / Prostate cancer / Prostatectomy / Prostatic Neoplasms - metabolism / Remission / Remission (Medicine) / Research and Analysis Methods / Resistance factors / Risk factors / Sensitizing / Sexual behavior / Signs and symptoms / Skeletal muscle / Spectroscopy / Spectrum analysis / Study Protocol