Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes.


Journal

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640

Informations de publication

Date de publication:
02 2022
Historique:
revised: 20 09 2021
received: 17 05 2021
accepted: 02 10 2021
pubmed: 26 11 2021
medline: 15 3 2022
entrez: 25 11 2021
Statut: ppublish

Résumé

Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24-1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94-1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR).

Identifiants

pubmed: 34820902
doi: 10.1002/jbmr.4466
pmc: PMC8828668
mid: NIHMS1752021
doi:

Substances chimiques

Lysine K3Z4F929H6

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

265-272

Subventions

Organisme : NIA NIH HHS
ID : R01 AG027012
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017482
Pays : United States
Organisme : NIA NIH HHS
ID : R56-AG-02-0618
Pays : United States
Organisme : NIA NIH HHS
ID : N01-AG-6-2103
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR012459
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG-02-7012
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG020618
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG028050
Pays : United States
Organisme : NIA NIH HHS
ID : N01-AG-6-2106
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG17482
Pays : United States
Organisme : NIA NIH HHS
ID : N01-AG-6-2101
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG028050
Pays : United States
Organisme : NINR NIH HHS
ID : R01-NR012459
Pays : United States

Informations de copyright

© 2021 American Society for Bone and Mineral Research (ASBMR).

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Auteurs

Ruban Dhaliwal (R)

Metabolic Bone Disease Center, State University of New York Upstate Medical University, New York, NY, USA.

Susan K Ewing (SK)

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.

Deepak Vashishth (D)

Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, New York, NY, USA.

Richard D Semba (RD)

Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ann V Schwartz (AV)

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.

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Classifications MeSH