# Bone marrow fat and skeletal health in type 2 diabetes

> **NIH VA IK2** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2020 · —

## Abstract

Dr. Kim’s long-term goal is to be a VA physician investigator, elucidating mechanisms of diabetic bone
disease in order to reduce fracture risk in people with diabetes. There is growing recognition that bone disease
is a complication of type 2 diabetes mellitus (T2DM). In T2DM, hip fracture risk is increased by more than a
third, and after fracture, individuals with T2DM have higher rates of postoperative complications and a higher
risk of mortality. Fracture risk is elevated even after controlling for falls, and hip fractures occur despite
preserved or higher bone mineral density (BMD). The fat within the bone marrow is proposed to play a
pathogenic role in diabetic bone disease, as fat and bone are intimately related within the marrow
microenvironment. Adipocytes and osteoblasts share a common mesenchymal stem cell precursor, and
adipogenesis could occur at the expense of osteoblastogenesis. Indeed, greater levels of marrow fat content
are associated with lower BMD and higher fracture risk. However, it is unknown whether marrow fat can be
manipulated to improve diabetic bone disease. Hemoglobin A1c (HbA1c) positively correlates with higher
levels of marrow fat, so enhanced glycemic control might normalize marrow fat and improve bone outcomes.
Given the widespread prevalence of diabetes and the medical and economic costs of fractures, there is an
urgent need to understand diabetic bone disease to identify targeted preventive and therapeutic strategies.
 During the Career Development Award-2 (CDA-2) period, Dr. Kim’s goal is to acquire the training and
implement the studies needed to understand the effects of improved glycemic control on marrow fat and bone
health. She will gain expertise in valuable clinical research and translational methods that will position her to
become a leader in the field of diabetic bone disease. Dr. Kim will enroll and follow 75 Veterans with poorly
controlled T2DM (HbA1c 8.5-12.0%) who are working with their clinicians to improve glycemic control. She will
determine the effects of improved glycemic control on bone marrow fat (Aim 1) and the relationship between
changes in marrow fat with bone quality and mass (Aim 2). Pursuit of these aims will involve critical training in
the design and implementation of a prospective cohort study. Dr. Kim will use advanced and sensitive imaging
modalities (including magnetic resonance spectroscopy, high-resolution peripheral quantitative computed
tomography) to assess marrow fat and bone outcomes at baseline and then after 1 year of intensified medical
management. Dr. Kim will also use cutting edge translational methods to explore the role of osteoblast
differentiation as a pathway linking marrow fat and bone outcomes (Aim 3). This will include characterizing
circulating osteoblast progenitor cells by flow cytometry and evaluating expression of osteoblast differentiation
genes. Training in advanced diabetes and lipid metabolism will allow Dr. Kim to interpret these findings and
gain...

## Key facts

- **NIH application ID:** 9891879
- **Project number:** 1IK2CX001984-01A1
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Tiffany Youngun Kim
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891879

## Citation

> US National Institutes of Health, RePORTER application 9891879, Bone marrow fat and skeletal health in type 2 diabetes (1IK2CX001984-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891879. Licensed CC0.

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