Adolescent Girls with Type 1 Diabetes Develop Changes in Bone Prior to Evidence of Clinical Neuropathy

Context: Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease. Methods: We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n = 21) and associated controls (n = 12). Groups were well matched for age, height, strength, and physical activity. Results: By high-resolution peripheral quantitative computed tomograpy, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, P-adj =. 095) and the tibia (-12.8%, P-adj =. 017) and decreased trabecular thickness (-8.3% radius, P-adj =. 007; -7.5% tibia, P-adj =. 034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (P-adj =. 024) and porosity was decreased by 52.9% with T1D (P-adj =. 012). There were no significant differences in bone density by dual-energy x-ray absorptiometry. Participants with T1D also had lower circulating levels of osteocalcin (-30%, P =. 057), and type I collagen cross-linked C-telopeptide (-36%, P =. 035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone. Conclusion: Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related comorbidities later in life.