Biochemical Markers of Bone Turnover in Older Adults With Type 1 Diabetes

Mishaela R. Rubin*, Ian H. De Boer, Jye Yu C. Backlund, Valerie Arends, Rose Gubitosi-Klug, Amisha Wallia, Naina Sinha Gregory, Annette Barnie, Andrew J. Burghardt, John M. Lachin, Barbara H. Braffett, Ann V. Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Context: Type 1 diabetes (T1D) is characterized by high fracture risk, yet little is known regarding diabetes-related mechanisms or risk factors. Objective: Determine whether glycemic control, advanced glycation end products (AGEs), and microvascular complications are associated with bone turnover markers among older T1D adults. Design: Cross-sectional. Setting: Epidemiology of Diabetes Interventions and Complications study (6 of 27 clinical centers). Participants: 232 T1D participants followed for >30 years. Exposures: Glycemic control ascertained as concurrent and cumulative hemoglobin A1c (HbA1c); kidney function, by estimated glomerular filtration rates (eGFR); and AGEs, by skin intrinsic fluorescence. Main Outcome Measures: Serum procollagen 1 intact N-terminal propeptide (PINP), bone-specific alkaline phosphatase (bone ALP), serum C-telopeptide (sCTX), tartrate-resistant acid phosphatase 5b (TRACP5b), and sclerostin. Results: Mean age was 59.6 ± 6.8 years, and 48% were female. In models with HbA1c, eGFR, and AGEs, adjusted for age and sex, higher concurrent HbA1c was associated with lower PINP [β -3.4 pg/mL (95% CI -6.1, -0.7), P = 0.015 for each 1% higher HbA1c]. Lower eGFR was associated with higher PINP [6.9 pg/mL (95% CI 3.8, 10.0), P < 0.0001 for each -20 mL/min/1.73 m2 eGFR], bone ALP [1.0 U/L (95% CI 0.2, 1.9), P = 0.011], sCTX [53.6 pg/mL (95% CI 32.6, 74.6), P < 0.0001], and TRACP5b [0.3 U/L (95% CI 0.1, 0.4), P = 0.002]. However, AGEs were not associated with any bone turnover markers in adjusted models. HbA1c, eGFR, and AGEs were not associated with sclerostin levels. Conclusions: Among older adults with T1D, poor glycemic control is a risk factor for reduced bone formation, while reduced kidney function is a risk factor for increased bone resorption and formation.

Original languageEnglish (US)
Pages (from-to)E2405-E2416
JournalJournal of clinical endocrinology and metabolism
Issue number6
StatePublished - Jun 1 2022


  • advanced glycation end products
  • bone turnover markers
  • diabetic peripheral neuropathy
  • estimated glomerular filtration rates
  • proliferative diabetic retinopathy
  • skin intrinsic fluorescence

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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