# Gaining Metabolic Insight in Older Men undergoing Androgen Deprivation Therapy for Prostate Cancer

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $416,443

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of this proposal is to determine the predominant anatomic site (liver or skeletal muscle) of
insulin resistance and the mechanisms that lead to its development in men with prostate cancer (PCa)
undergoing androgen deprivation therapy (ADT). As testosterone has a central role in the stimulation of
prostate tissue, ADT is the cornerstone of treatment in men with high grade and metastatic PCa. ADT results in
castrate levels of serum testosterone and this profound androgen deficiency leads to an increase in both
visceral and subcutaneous fat mass, and a reduction in skeletal muscle mass. These unfavorable changes in
body composition result in the development of insulin resistance and cardiovascular disease. These metabolic
perturbations follow an aggressive course in these men as insulin resistance develops within 8 weeks of
starting ADT. These adverse metabolic changes have significant consequences as men on ADT have a higher
risk of cardiovascular disease including coronary artery disease, myocardial infarction, peripheral vascular
disease and sudden cardiac death compared with those men with PCa who do not undergo ADT and are only
treated with prostatectomy (non-ADT group). Indeed, cardiovascular disease has become the leading cause of
mortality in these men. Although insulin resistance is the seminal event in this metabolic cascade, the
predominant site and the mechanisms behind its development (such as the role of parenchymal fat infiltration
and inflammatory cytokines) remain unknown in this patient population. As men undergoing ADT are old, frail
and have multiple co-morbidities, the option of physical exercise is limited in these men. Hence, unveiling the
site and the mechanisms of this resistance will guide physicians to prevent insulin resistance by initiating
"tissue-specific" insulin sensitizing drugs in the future. We propose a prospective, 6-month, observational
cohort study in which we will: 1) determine the predominant site of insulin resistance by using a validated,
state-of-the-art, oral glucose tolerance test, and 2) determine the mechanism of insulin resistance by
measuring hepatic and intramyocellular fat (using magnetic resonance spectroscopy) and measuring
circulating inflammatory cytokines (known to induce insulin resistance in other populations) by using validated
assays. The information obtained from this study will not only lead to future mechanistic studies at the cellular
level of the implicated organ, but also lay the framework for clinical trials evaluating the role of evolving tissue-
specific insulin-sensitizers and novel anti-inflammatory drugs in the prevention and treatment of insulin
resistance, which in turn, will prevent cardiovascular disease in these men.

## Key facts

- **NIH application ID:** 9994267
- **Project number:** 5R01CA226211-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shehzad Basaria
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,443
- **Award type:** 5
- **Project period:** 2018-09-04 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994267

## Citation

> US National Institutes of Health, RePORTER application 9994267, Gaining Metabolic Insight in Older Men undergoing Androgen Deprivation Therapy for Prostate Cancer (5R01CA226211-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9994267. Licensed CC0.

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