Bone Quality in Patients with Long-Standing Type 1 Diabetes

ABSTRACT
Subjects with type 1 diabetes (T1D) have three- to six-fold higher fracture risk compared with subjects without
diabetes, and although bone mineral density (BMD) – the clinical standard to assess osteoporosis and fracture
risk – is lower in subjects with T1D compared to controls, BMD alone cannot explain the disproportionate
increase in fracture risk associated with T1D. The risk of fracture in middle-age and older subjects with long-
standing T1D might be compounded by young-onset T1D, the accumulation of advanced glycation end
products (AGEs) due to chronic hyperglycemia, or by a potential superimposition of aging and long-term T1D
effects on bone. The “Bone Health in Adults with Type 1 Diabetes” study (R01DK122554) aims to explore BMD
and bone strength at the hip using quantitative computed tomography (QCT) in subjects with long-standing
T1D and age-, sex- and body mass index-matched controls, as well as to investigate the effects of chronic
hyperglycemia and hypoglycemia on bone health. However, bone strength – the main determinant of bone
fracture – is determined by BMD, bone quality, and its microenvironment including bone marrow adipose
tissue. Therefore, we propose an ancillary study to the “Bone Health in Adults with Type 1 Diabetes” parent
study and leverage its well-characterized cohort of subjects, clinical, laboratory, and imaging data to assess
phenotypes of bone marrow adiposity (BMA) and bone microstructure in middle-age and older subjects with
long-standing T1D using advanced imaging and image analysis techniques. Using chemical shift-based water-
fat separation magnetic resonance imaging and high-resolution peripheral quantitative computed tomography
(HR-pQCT) we aim to assess differences in 24-month changes in BMA at the proximal femur and in bone
microstructure at the distal radius and distal tibia between middle-age and older subjects with long-standing
T1D and controls without diabetes. Furthermore, differences in the spatial distribution of 24-month changes in
BMA between the two groups will be investigated using voxel-based morphometry; and the associations of
chronic hyperglycemia and hypoglycemia with 24-month changes in BMA and bone microstructure will also be
explored. Due to the increase incidence of T1D and improved medical care, the life expectancy of subjects with
T1D is expected to increase, and although subjects with T1D have an increased risk of fracture during the
entire life, most fractures occur at older age when the total fracture burden is greatest in the general
population. Therefore, there is a critical need to better understand the etiology of T1D-related bone disorders to
develop clinical strategies to prevent clinically and economically costly fractures in this large vulnerable
population.

Grant Number: 5R01AR080423-04
NIH Institute/Center: NIH
Principal Investigator: Julio Carballido-Gamio