Geriatric Research Education and Clinical Center - Research

This page shows the research that Eastern Colorado GRECC is and has done and how it promotes the priorities of the VA, specifically Geriatrics and Extended Care. The VA Geriatrics and Extended Care website highlights the areas of most concern to our Veterans and their caregivers. What we have done here is demonstrate the areas where our research supports and promotes these areas. We are not engaged in research for each area but where we are involved in an area we are deeply involved.

The research focus at Eastern Colorado GRECC is geriatric obesity focused on metabolism, mobility and exercise, especially as this relates to female Veterans. Translating this to the VA Geriatrics and Extended Care areas we find our work centered in these areas:

• Home and Community Services
• Residential Settings and Nursing Homes
• Making Decisions and Advance Care Planning
  • Patient Priorities - What matters to you
  • Hospice Care
• Health, Fitness, Rehabilitation
  • Geriatric Evaluation
  • Rehabilitation and Prosthetic Services
  • Telehealth
  • Whole Health & Well-Being
• For Health Care Professionals: Age-Friendly Health Systems
• Pre-Clinical Research: Obesity

Residential Settings and Nursing Homes

Advancing Rehabilitation Paradigms for Older Adults in Skilled Nursing Facilities
This study seeks to provide large-scale, foundational evidence that high-intensity rehabilitation is effective and be systematically implemented to improve functional outcomes for patients admitted to skilled nursing facilities following hospitalization. 
Additionally, this study will generate a descriptive overview of factors that predict implementation success while informing effective implementation strategies for future skilled nursing facilities innovation. 
Overall, this study is a critical step in advancing clinical practice to establish high-intensity rehabilitation as an effective standard of care in skilled nursing facilities to shift current treatment away from low-intensity, conservative interventions.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: National Institute on Aging

Making Decisions and Advance Care Planning: Patient Priorities - What matters to you

Decision trajectories of patients at the end of life: An epidemiological exploration of MAID and the impact on caregivers and clinicians
A broad population now has access to Medical Aid in Dying (MAiD). Yet, knowledge of the epidemiologic, experiential, and decision-making characteristics of individuals considering and pursuing MAiD needs to be improved and may be critical to informing evidence-based policies and practices. Furthermore, understanding the perspectives of family members/caregivers and clinicians caring for MAiD patients will help inform support after these experiences.
Investigator: Daniel Matlock, MD
Funder: National Institute on Aging
NIH website

Decision Making Among Older Adults: the AUTO study
Deciding when to “hang up the car keys” is one of the most emotional and difficult decisions older adults face, especially in the context of age-associated cognitive impairment, such as Alzheimer’s disease. Yet, it is also one that almost every individual, and their family, must wrestle with. 
A web-based decision aid could help older adults make informed decisions about driving that align with personal values. Understanding which types of older adults benefit most from the decision aid, along with when to use the decision aid, will help optimize real-world use.
Such a decision aid may be necessary for individuals with cognitive impairment, such as that associated with Alzheimer’s disease, particularly in its earliest stages. The condition may complicate driving decisions and increase driving risk and the need for eventual driving cessation.
Investigator: Marian (Emmy) Betz, MD, MPH
Funder: National Institute on Aging
NIH website
Publications of note:
— Cars, Guns, Aging, and “Giving Up the Keys”
— The Advancing Understanding of Transportation Options (AUTO) study: design and methods of a multi-center study of decision aid for older drivers

Novel Strategies for Personalized Clinical Decisions in Knee Arthroplasty
The proposed research is relevant to public health because total knee arthroplasty (TKA) is the most common inpatient elective surgery, with approximately 700,000 procedures performed each year. 
We propose to develop and implement a clinical decision tool for shared decision-making — Personalized Reference Charts (PRCS) — to facilitate personalized approaches to care. We believe our research will contribute to AHRQ's mission by supplying knowledge that will enhance individual clinical decision-making, increase resource utilization efficiency, and improve the quality of care surrounding TKA surgery in a learning healthcare system.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: Agency for Healthcare Research and Quality
NIH website
Publications of note:
— Person-Centered Care and Physical Therapy: A “People-Like-Me” Approach
— "This is not negotiable. You need to do this…": A directed content analysis of decision making in rehabilitation after knee arthroplasty

A Multicenter Trial of a Shared DECision Support Intervention for Patients offered implantable Cardioverter-DEfibrillators: DECIDE - ICD Trial
Strong scientific evidence supports the idea that shared decision-making is achieved through patient decision aids. However, many attempts at real-world implementation have failed due to a focus on low-risk decisions in primary care where clinicians are either too busy or the stakes are too low for the decision aid to be valuable. 
This team's overall goal is to assess the real-world effectiveness and implementation of patient decision aids for high-risk decisions using the implantable cardioverter-defibrillator (ICD) as a model. 
By simultaneously exploring effectiveness and implementation, this project will provide practical information that will inform a growing national agenda to involve patients in their health care via shared decision-making.
Investigator: Daniel Matlock, MD
Funder: National Heart, Lung, and Blood Institute
NIH website
Website: IDECIDE - Left Ventricular Assist Device (LVAD)
Publications of note:
— Shared Decision Making in Cardiac Electrophysiology Procedures and Arrhythmia Management
— Mandates for Shared Decisions: Means to which Ends?
— Shared Decision Making for Left Ventricular Assist Devices: Rationale and Design of a Nationwide Dissemination and Implementation Project

Improving Rehabilitation for Veterans After Total Knee Arthroplasty Using Individualized Recovery Trajectories
This study will examine the impact of a new clinical decision-support tool for rehabilitation after total knee arthroplasty (TKA). Typically, TKA rehabilitation is generic. Most patients receive the same dose and type of rehabilitation, despite the diversity of patients who undergo TKA. 
Our clinical support decision tool helps physical therapists tailor rehabilitation treatments and dosages to the individual needs, goals, and preferences of Veterans recovering from TKA. This study can potentially improve Veterans’ functional recovery after TKA while reducing the average number of physical therapy visits Veterans attend after surgery by tailoring rehabilitation dosage based on need. 
The clinical support decision tool will ensure the Veterans Health Administration (VHA) has the resources and capacity to provide adequate rehabilitation to every Veteran seeking TKA in the VHA system. Physical therapists using the clinical decision support tool can improve outcomes and access for other patient populations in the future.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: Veterans Affairs
NIH website

Hospitals Use Shared Decision Making with Patients Considering LVAD Treatment
 

Heart failure occurs when the heart doesn’t pump blood as it should. In advanced heart failure, people feel shortness of breath and other symptoms even at rest. An LVAD is a battery-powered pump that doctors implant in the heart to help people with advanced heart failure live longer. But LVADs have serious risks, such as stroke, bleeding, and infection. In addition, people who get LVADs need help from a caregiver and must change their lifestyle. Patients must understand these trade-offs to make the best decisions for themselves.
This PCORI-funded implementation project is expanding the use of a shared decision-making program, shown to help patients with advanced heart failure decide whether to get a left ventricular assist device or LVAD, to LVAD clinics across the United States.
Investigator: Daniel Matlock, MD
Funder: Patient-Centered Outcomes Research Institute (PCORI)
PCORI Website

Making Decisions and Advance Care Planning: Hospice Care

Pilot Evaluation of Hospice Decision Support Tools
Hospice is misunderstood and underutilized. No quality decision aids for patients and families considering hospice are currently available. This research project addresses this critical gap in quality patient-centered care for people facing end-of-life decisions by testing the feasibility, acceptability, and preliminary efficacy of a novel hospice patient decision aid developed by the study team.
Investigator: Daniel Matlock, MD
Funder: National Institute on Aging
NIH website
Website: Hospice - A decision aid for patients considering Hospice care
Publications of note:
— How Do Patients Describe Hospice Care? A Qualitative Analysis of the Language Used by Older Adults to Describe Hospice Care
— Development of a Decision Aid for Patients and Families Considering Hospice

Health, Fitness, Rehabilitation: Geriatric Evaluation

Detection and Treatment of Sarcopenia and Myosteatosis in Older African Americans
This project aims to improve the detection and treatment of age-related changes in muscle mass and quality in older African Americans. Muscle abnormalities in older adults often remain undetected until an injury or a disabling event occurs. The assessment of muscle wasting only after the manifestation of weakness is an inadequate screening model. Moreover, health disparities in African Americans concerning type 2 diabetes and age-related declines in functional performance may show changes in muscle quality. 
Therefore, the objectives of this VA Historically Black College and University career development project are to:
1) develop a rapid, portable, cost-effective method for assessing muscle mass and quality using ultrasound imaging and 
2) demonstrate how an innovative form of strength training that is appropriate for older adults can reverse age-related changes in muscle mass and quality. 
Completing this project will aid the identification of risk factors for age-related muscle wasting and expand the approach to exercise-based interventions.
Investigator: Michael Harris-Love, PT, MPT, DSc, FGSA
Funder: Veterans Affairs
NIH website
Publications of note:
— Eccentric Exercise: Adaptations and Applications for Health and Performance
— Rate of Force Development Is Related to Maximal Force and Sit-to-Stand Performance in Men With Stages 3b and 4 Chronic Kidney Disease

Health, Fitness, Rehabilitation: Rehabilitation and Prosthetic Services

Enhancing Skeletal Adaptation to Exercise by Attenuating the Acute Disruption of Calcium Homeostasis During Exercise
Exercise is essential for building and maintaining bone mass and strength. Still, current recommendations for achieving this need more detail on the optimal exercise prescription. Recent studies found that blood calcium level decreases during exercise and that calcium is mobilized from bone to slow the decline. If this repeatedly occurs during exercise training, it could diminish the potential benefits of exercise to improve bone health. 
The proposed studies will determine whether taking supplemental calcium before exercise to minimize the decline in blood calcium levels is an effective way to improve the skeletal benefits of exercise. This research is essential for Veterans because they are at increased risk of hip fracture compared to non-Veterans. Further, because osteoporosis in men is under-recognized and under-treated, providing male (and female) Veterans with more specific exercise and nutrition guidelines can enhance bone health, reduce fracture risk, and improve quality of life.
Investigator: Wendy M. Kohrt, PhD 
Funder: Veterans Affairs
NIH website

Improving Function in Older Veterans with Hospital-associated Deconditioning
This study focuses on a prevalent and understudied problem for older Veterans: functional decline following acute hospitalization. Our proposed intervention will be applied in the immediate post-hospitalization period to lessen the effects of deconditioning for older Veterans and improve home and community mobility. 
The intervention also has the potential to reduce the utilization of high-cost, long-term healthcare options such as formal in-home caregivers or institutionalization within the Veterans Health Administration System. 
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: Veterans Affairs
NIH website
Publications of note:
— Public Health Impact of Frailty: Role of Physical Therapists

Improving Rehabilitation Outcomes After Total Hip Arthroplasty
In the next two decades, there may be a significant increase in total hip arthroplasty (THA) surgeries. Innovative rehabilitation techniques are needed to optimize long-term physical function. 
This study has a high potential to change current rehabilitation practice for THA in Veterans where implementing functional strength integration rehabilitation strategies can be designed for clinical settings. 
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: Veterans Affairs
NIH website
Publications of note:
— Trunk movement compensation identified by inertial measurement units is associated with deficits with physical performance, muscle strength and functional capacity in people with hip osteoarthritis
— Incorporating Specific Functional Strength Integration Techniques to Improve Functional Performance for Veterans After Total Hip Arthroplasty: Protocol for a Randomized Clinical Trial
— Simulated Hip Abductor Strengthening Reduces Peak Joint Contact Forces in Patients with Total Hip Arthroplasty
— The Impact of Hip Implant Alignment on Muscle and Joint Loading during Dynamic Activities

Optimizing Physical Activity Outcomes for Veterans After Total Knee Arthroplasty
While total knee arthroplasty improves the pain and disability associated with knee osteoarthritis, physical activity levels after total knee arthroplasty remain at low levels and are nearly unchanged from before surgery. Such low physical activity may account for problems seen in Veterans with total knee arthroplasty, including long-term disability, secondary health problems, and high levels of healthcare use. 
There is a clear need to advance current rehabilitation strategies to address chronic low physical activity after total knee arthroplasty. Our proposed study will assess the efficacy of using physical activity behavior-change telerehabilitation for improving physical activity outcomes. The three-month intervention focuses on changing habitual behaviors through remote video telerehabilitation sessions between Veterans and physical therapists. 
This innovative approach shifts the paradigm of conventional rehabilitation to specifically target poor physical activity behaviors underlying physical disability for Veterans with total knee arthroplasty. 
Investigator: Cory Christiansen, PT PhD
Funder: Veterans Affairs
NIH website
Publications of note:
— Improving Physical Activity Through Adjunct Telerehabilitation Following Total Knee Arthroplasty: Randomized Controlled Trial Protocol

Optimizing Gait Rehabilitation for Veterans with Non-Traumatic Lower Limb Amputation
The population of older Veterans with non-traumatic lower limb amputation is growing. Following lower limb amputation, asymmetrical movements persist during walking and likely contribute to disabling sequelae, including secondary pain conditions, poor gait efficiency, impaired physical function, and compromised skin integrity of the residual limb. 
The proposed study seeks to address chronic gait asymmetry by evaluating the efficacy of two error-manipulation gait training programs to improve gait symmetry for Veterans with non-traumatic lower limb amputation. Additionally, this study will assess the potential of error-manipulation training programs to strengthen secondary measures of disability and residual limb skin health. 
Ultimately, the proposed study aims to improve conventional prosthetic rehabilitation for Veterans with non-traumatic amputation through gait training programs based on motor learning principles, resulting in improved gait symmetry and lower incidence of long-term disability after non-traumatic lower limb amputation.
Investigator: Cory Christiansen, PT PhD
Funder: Veterans Affairs
NIH website
Publications of note:
— Error-manipulation Gait Training for Veterans with Non-traumatic Lower Limb Amputation: A Randomized Controlled Trial Protocol

Movement pattern biofeedback training after total knee arthroplasty
In the next two decades, there may be a significant increase in total knee arthroplasty surgeries. Yet innovative rehabilitation techniques are still needed to optimize long-term physical function.
This study has a high potential to change current rehabilitation practices for TKA. Implementing movement pattern training can be easily implemented in clinical settings. Furthermore, the study also has the unique opportunity to improve patient outcomes after TKA by reducing subsequent problems due to compensatory overuse of the opposite knee.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: National Institute on Aging
NIH website
Publications of note:
— Multimodal conservative management of arthrofibrosis after total knee arthroplasty compared to manipulation under anesthesia: a feasibility study with retrospective cohort comparison
— Movement Pattern Biofeedback Training after Total Knee Arthroplasty: Randomized Clinical Trial Protocol
— The Impact of Home Health Physical Therapy on Medicare Beneficiaries with a Primary Diagnosis of Dementia

Progressing Home Health Rehabilitation Paradigms for Older Adults
This study focuses on a prevalent and understudied problem for older adults: mobility limitations in older adults following acute hospitalization. 
This investigation has a high potential for an immediate clinical impact because it addresses patient mobility in a home setting (rather than a laboratory) and is designed to work within existing Medicare reimbursement guidelines. 
The intervention also has the potential to reduce the utilization of high-cost healthcare options such as re-hospitalizations, nursing home stays, and emergency room visits.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: National Institute of Nursing Research
NIH website
Publications of note:
— Cardiac Rehabilitation in Frail Older Adults With Cardiovascular Disease: A NEW DIAGNOSTIC AND TREATMENT PARADIGM
— Progressive Multicomponent Intervention for Older Adults in Home Health Settings Following Acute Hospitalization: Randomized Clinical Trial Protocol

Improving health self-management using walking biobehavioral intervention for people with dysvascular lower limb amputation
Sedentary lifestyles and high levels of disability are relevant public and personal health issues resulting from the chronic comorbid condition of dysvascular lower limb amputation. 
This study examines the use of an evidence-based walking biobehavioral intervention to increase physical activity after dysvascular amputation. 
The proposed intervention leverages successes in conventional prosthetic rehabilitation while addressing the complex health conditions and chronic sedentary behaviors that underlie dysvascular amputation, with the ultimate goal of improved physical activity self-management to minimize disability.
Investigator: Cory Christiansen, PT PhD
Funder: National Institute of Nursing Research
NIH website

Health, Fitness, Rehabilitation: Telehealth

Walking Exercise Sustainability Through Telehealth for Veterans with Lower-Limb Amputation
Despite recent advances in physical rehabilitation, Veterans with lower-limb amputation have poor long-term outcomes, including severely limited functional capacity and high levels of disability. Such poor outcomes are compounded by a lack of exercise participation over time, even with lower-limb prostheses.
There is a clear need to advance current rehabilitation strategies to promote sustained exercise following lower-limb amputation. Our study will determine the efficacy of a walking exercise self-management program to achieve sustained exercise participation. The 18-month intervention on helping Veterans reduce habitual sedentary behavior through a remote exercise behavior-change intervention includes multiple clinical disciplines, a novel individualized exercise self-management training, and peer support. 
This innovative approach shifts the conventional rehabilitation paradigm to target life-long exercise sustainability and remove an underlying cause of disability for Veterans with lower-limb amputation.
Investigator: Cory Christiansen, PT PhD
Funder: Veterans Affairs
NIH website

Engaging Medically Complex Veterans in Tele-Rehabilitation Using a Biobehavioral Approach: A Pilot Study of Feasibly and Acceptability
Medically complex older Veterans are a vulnerable patient population with reduced access to care (i.e., rural living and limited transportation). This population is also at risk for physical function deficits, physical inactivity, and social isolation.
Telerehabilitation is a potentially effective and scalable approach for providing rehabilitation services to medically complex older Veterans with limited care access. This study will determine the feasibility, acceptability, and safety of a multicomponent telerehabilitation program strategically designed to address the physical function deficits and social isolation often experienced by older Veterans.
Study findings will have an immediate clinical impact as they will guide the implementation of safe and effective telerehabilitation strategies for medically complex older Veterans who lack access to standard in-person rehabilitation services.
Investigator: Jennifer Stevens-Lapsley, PT, PhD, FAPTA
Funder: Veterans Affairs
NIH website

Expanding Exercise Programming for Veterans Through Telehealth
Exercise is an evidence-based intervention for managing chronic conditions, yet the majority of Veterans are inactive. Group telehealth (GT) delivered exercise can improve access to and participation in exercise. 
Telehealth-delivered exercise programs typically have initiation and maintenance phases. Skills for exercise initiation and maintenance differ, and interventions that focus on one or the other are not likely to result in sustained exercise participation. 
The Veterans Health Administration is the largest integrated health care system in the US, and implementing successful exercise programs could profoundly impact public health. 
GT exercise combines the benefits of group exercise sessions, such as social support and telehealth technology. No studies compare GT exercise booster sessions plus text messaging to text messaging alone to support exercise maintenance. 
Gerofit, an existing telehealth-delivered VA exercise program implemented at multiple sites, will be used as a model. A future larger, single-site trial will test the effectiveness and evaluate the implementation of the GT exercise initiation and maintenance intervention.
Investigator: Lauren Abbate, MD PhD
Funder: Veterans Administration
NIH website
VA HSR&D website

Health, Fitness, Rehabilitation: Whole Health & Well-Being

Workforce Development Engages Diverse Older Adults to Catalyze Innovative Approaches for Enhanced Recruitment and Retention
We will recruit, train and hire diverse older adults into paid positions as research specialists. They are part of the enhanced clinical research infrastructure, which will help catalyze innovative solutions to mitigate existing cultural divides between potential study participants and research professionals caused by differences in age, socio-economic status, education levels, rural versus urban locality, and health literacy. 
Leveraging this enhanced capacity, we will host Research Roadshow events to engage diverse older adults throughout rural/frontier communities in Colorado, providing fun, experiential opportunities to engage with research and research teams. 
We will promote enduring connections with diverse communities through expanded community outreach and engagement programming, enhanced facilitation of the informed consent process, and tailored communication strategies.
Investigator: Kathryn Nearing, PhD, MA
Funder: National Institute on Aging
NIH website

MitoQ supplementation for restoring aerobic exercise training effects on endothelial function in postmenopausal women
Regular exercise is associated with a reduced cardiovascular disease (CVD) risk. It is a therapeutic intervention for improving vascular health. Although regular aerobic exercise improves vascular health in older men, it has not consistently improved vascular health in older women. 
The proposed studies will test the efficacy of administering a mitochondrial-targeted antioxidant (MitoQ) for restoring exercise training benefits on endothelial function in estrogen-deficient postmenopausal women.
Investigator: Kerrie Moreau, PhD
Funder: National Institute on Aging
NIH website

Comparison of Exercise Mode on Disruptions in Calcium Homeostasis
Endurance exercise can improve cardiometabolic health, maintain bone health throughout life, and prevent osteoporotic fractures. However, evidence suggests that bone does not always adapt as expected. Endurance exercise may lead to bone loss under certain conditions. 
Disruptions in calcium homeostasis during exercise may explain this observation. Preliminary data suggests that the mode of exercise (i.e., cycling versus treadmill) may result in different magnitudes of change in bone biomarkers. 
This study aims to determine if the mode of exercise results in a differential bone biomarker response to an acute exercise bout in older Veterans. 
Blood samples will be collected before, during, and after two acute exercise bouts: 1) brisk treadmill walking; and 2) vigorous stationary cycling. 
This data will help develop future exercise interventions in older Veterans to preserve cardiometabolic and bone health.
Investigator: Sarah Wherry, PhD
Funder: Veterans Affairs
NIH website

For Health Care Professionals: Age-Friendly Health Systems

IMPlementation to Achieve Clinical Transformation (IMPACT): The Colorado Training Program
We propose a training program to develop faculty who can carry out "T4 research". T4 research addresses how best to implement interventions of proven effectiveness in actual clinical settings. 
Our program provides in-depth, individually tailored training for scholars using classroom activity (courses, seminars, and workshops) and intensive embedded research experiences in two of the five partner settings conducting clinical research in heart, lung, blood, and sleep disorders.
Investigator: Russ Glasgow, PhD
Funder: National Heart, Lung, and Blood Institute
NIH website
Publications of note:
— Pragmatic considerations and approaches for measuring staff time as an implementation cost in health systems and clinics: key issues and applied examples
— How Dissemination and Implementation Science Can Contribute to the Advancement of Learning Health Systems
— Stakeholder perspectives on current determinants of ultrasound-guided thoracentesis in resource limited settings: a qualitative study
— Using Iterative RE-AIM to enhance hospitalist adoption of lung ultrasound in the management of patients with COVID-19: an implementation pilot study

Pragmatic Implementation Science Approaches to Assess and Enhance Value of Cancer Prevention and Control in Rural Primary Care
We propose an Implementation Science Center for Cancer Control focusing on developing, validating, and sharing innovative, pragmatic models and methods related to the costs, benefits, and value of translating evidence-based cancer control programs and guidelines into rural primary care practice settings. 
Our theme is `Pragmatic implementation science approaches to assess and enhance the value of cancer prevention and control in rural primary care.' 
These approaches will inform strategies to implement lung cancer screening and other cancer prevention and control interventions and advance implementation science by providing measures, reporting guides, resources, training, and certification of competence.
Investigator: Russ Glasgow, PhD
Funder: National Cancer Institute
NIH website
Publications of note:
— Lung cancer screening in rural primary care practices in Colorado: time for a more team-based approach?
— Creating research-ready partnerships: the initial development of seven implementation laboratories to advance cancer control
— Speeding implementation in cancer: The National Cancer Institute’s Implementation Science Centers in Cancer Control
— Pragmatic considerations and approaches for measuring staff time as an implementation cost in health systems and clinics: key issues and applied examples

Integrative Physiology of Aging Training Grant
This Integrative Physiology of Aging T32 will train the next generation of clinicians and physiologists to understand better and investigate the specific needs/concerns of an aging population. 
This T32 emphasizes:
1. Co- mentoring of trainees by Primary and Secondary mentors.
2. Carefully constructed career development plans.
3. Exposure to leadership and “team training” skills to maximize future scientific impact.
Investigator: Kerrie Moreau, PhD
Funder: National Institute on Aging
NIH website
Publications of note:
— Stakeholder and Data Driven Fall Screen in a Program of All-Inclusive Care for the Elderly: Quality Improvement Initiative
— Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone
— Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults

Pre-Clinical Research: Obesity

Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes
Obesity is prevalent among US military Veterans and linked to an increased incidence of cardiovascular disease, diabetes, pulmonary disorders, and certain forms of cancer. As the veteran population ages, diminished production of the primary sex hormone, estrogen, promotes fat accumulation in menopausal women.
We discovered a subpopulation of adipocytes in humans and mice termed bone marrow-derived adipocytes (BMDAs) that exhibit an inflammatory character. These unique adipocytes are more abundant in female than male mice. They are increased by the loss of estrogen in female mice. These observations led us to hypothesize that BMDAs provide a link between sex hormone-related changes in adiposity and body-wide inflammation. 
This project will test this hypothesis in mice in which estrogen signaling is suppressed and in which BMDAs and their progenitors are specifically ablated. Understanding the mechanisms by which sex hormones regulate BMDA and progenitor production holds the potential for therapies to prevent menopausal diseases in aging female veterans.
Investigator: Dwight Klemm, PhD
Funder: Veterans Affairs
NIH website
Publications of note:
— Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
— Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue
— Modulation of Energy Expenditure by Estrogens and Exercise in Women

Integrin signaling promotes production of adipocytes from hematopoietic cells
Obesity is a major medical problem for which there are few effective therapies. 
This project will investigate the processes and events that control the production of potentially harmful fat cells. Successful completion of these studies will identify new targets for controlling the production of harmful fat-storing cells and prevent fat-related chronic disease.
Investigator: Dwight Klemm, PhD
Funder: National Institute of Diabetes and Digestive and Kidney Diseases
NIH website
Publications of note:
— Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
— Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue

Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function
The decline in sex hormones (estrogen and testosterone) with aging can increase the risk for certain diseases; osteoporosis is a well-known example. The loss of estrogen is significant for women’s health because it occurs during mid-life. In contrast, the loss of testosterone in men occurs much later in life. 
The Colorado Specialized Center of Research Excellence on Sex Differences (CO-SCORE) will advance novel ideas for how the loss of estrogen increases fat gain in the abdominal region, which increases the risk for heart disease and diabetes, and strategies that may be effective in preventing this.
Investigator: Wendy M. Kohrt, PhD
Funder: National Institute on Aging
NIH website
Publications of note:
— Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone
— Sex Differences in Peripheral Artery Disease
— Body composition and cardiometabolic health across the menopause transition
— Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Cardiovascular Consequences of Hypogonadism in Men
The findings from this research should provide new information into whether declines in testosterone cause blood vessels and the heart in middle-aged and older men to become unhealthy. Moreover, determining the possible causes of cardiovascular health changes related to declines in testosterone may lead to the development of preventive and therapeutic strategies that favorably modify these factors and prevent or slow changes in vascular and cardiac health and decrease cardiovascular disease risk.
Investigator: Kerrie Moreau, PhD
Funder: National Institute on Aging
NIH website
Publications of note:
— Assessment of macrovascular and microvascular function in aging males
— Body composition and cardiometabolic health across the menopause transition
— Sex Differences in Peripheral Artery Disease