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, Ivana Shen Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO , USA Search for other works by this author on: Oxford Academic Rachel L Usala Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO , USA Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine , St. Louis, MO , USA Search for other works by this author on: Oxford Academic Mahshid Mohseni Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO , USA Search for other works by this author on: Oxford Academic Mary L Bouxsein Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA , USA Search for other works by this author on: Oxford Academic Deborah M Mitchell Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA , USA Search for other works by this author on: Oxford Academic Erica L Scheller Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO , USA Department of Cell Biology and Physiology, Washington University School of Medicine , St. Louis, MO , USA Department of Developmental Biology, Washington University School of Medicine , St. Louis, MO , USA Center of Regenerative Medicine, Washington University , St. Louis, MO , USA Corresponding: Erica L. Scheller, Address: 660 S. Euclid Ave., Campus Box 8301, St. Louis, MO 63110, Phone: 314-737-7511, Email: scheller@wustl.edu Search for other works by this author on: Oxford Academic
Ivana Shen and Rachel L. Usala contributed equally to this manuscript
Author Notes
The Journal of Clinical Endocrinology & Metabolism, dgae511, https://doi.org/10.1210/clinem/dgae511
Published:
26 July 2024
Article history
Received:
14 March 2024
Revision received:
30 May 2024
Editorial decision:
21 July 2024
Accepted:
23 July 2024
Published:
26 July 2024
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Ivana Shen, Rachel L Usala, Mahshid Mohseni, Mary L Bouxsein, Deborah M Mitchell, Erica L Scheller, Adolescent girls with type 1 diabetes develop changes in bone prior to evidence of clinical neuropathy, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae511, https://doi.org/10.1210/clinem/dgae511
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Abstract
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 HR-pQCT, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, p-adj=0.095) and the tibia (-12.8%, p-adj=0.017) and decreased trabecular thickness (-8.3% radius, p-adj=0.007; -7.5% tibia, p-adj=0.034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (p-adj=0.024) and porosity was decreased by 52.9% with T1D (p-adj=0.012). There were no significant differences in bone density by DXA. Participants with T1D also had lower circulating levels of osteocalcin (-30%, p=0.057), and type I collagen cross-linked C-telopeptide (-36%, p=0.035), 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 co-morbidities later in life.
Bone/Mineral Metabolism, Metabolic bone disease, Pediatric endocrinology, Diabetes, Complications, Microvascular, Neuropathy, Type 1 Diabetes
Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.
This content is only available as a PDF.
Author notes
Ivana Shen and Rachel L. Usala contributed equally to this manuscript
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.
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