Bone mineralization and microarchitecture in youth with type 1 diabetes

Osteoporosis is a well-described but often neglected complication of type 1 diabetes (T1DM). Adults with T1DM are at very high risk for fracture, and sub-optimal bone accrual in childhood may contribute significantly to this risk. Adolescence is a critical time for bone mineral accrual, with ~50% of peak bone mass acquired during the pubertal years and >90% by age 18_ENREF_10. Since T1DM typically presents in childhood, an effect of T1DM on bone formation has the potential to cause a significant deficit in peak bone mass and thus fracture resistance. To date, the pathogenesis of T1DM-associated bone fragility remains unclear. In particular, elevated hemoglobin A1c (HgbA1c) is inconsistently associated with lower bone mineral density in the available literature. In addition, a role for insulin-like growth factor 1 (IGF1), an important anabolic factor for bone which is suppressed in the setting of T1DM, has been suggested.

Objective The overall goal of this study is to determine whether T1DM leads to reduced bone formation and impaired bone microarchitecture during childhood, and to identify the underlying pathophysiology. I propose to prospectively study the rate of bone mineral accrual in adolescents with T1DM compared to age- and race-matched controls. I will use both dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) which will allow me to investigate the effects of T1DM on mineralization and microarchitecture of both the cortical and trabecular skeletal compartments.