As advances in clinical care continue to improve the lifespan of adults with type 1 diabetes (T1D), these patients have experienced an increase in aging-related diseases, including osteoporosis. As compared to nondiabetic adults, patients with T1D have an increased risk of fractures, particularly at the hip. This clinically important problem is further compounded by the fact that patients with T1D experience poorer outcomes following a fracture. However, little is currently known about the effect of T1D on bone composition and bone quality, particularly in older adults. In this proposal, our goal is to investigate biomechanical mechanisms of skeletal fragility in postmenopausal women and men age > or = to 50 years with T1D. We will compare tissue level bone biomechanical properties and bone composition using ex vivo femoral specimens from adults with longstanding T1D (50+ year duration) and matched nondiabetic controls, as well as from adults with and without T1D who are undergoing surgical repair of hip fracture. Using state-of-the-art methods, successful completion of our proposed aims will provide novel insights about the alterations in bone structure and quality that contribute to skeletal fragility in older adults with T1D, in whom fracture risk is highest. In addition, our findings will clarify the impact of diabetic history and accumulation of advanced glycation end-products on skeletal fragility in T1D. Addressing these critical gaps in knowledge will ultimately allow clinicians to develop rational approaches to prevent fractures in patients with T1D.

Public Health Relevance

The biomechanical factors contributing to the striking increase in hip fracture risk among older adults with type 1 diabetes (T1D) are poorly understood. We will evaluate femoral specimens to assess bone material properties in adults with longstanding T1D with and without hip fracture. Results from these studies will identify mechanisms underlying skeletal fragility in T1D and may help to direct treatments for this vulnerable population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
High Priority, Short Term Project Award (R56)
Project #
5R56DK122593-02
Application #
10017186
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Malozowski, Saul N
Project Start
2019-09-12
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114