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

Authors

Mishaela R. Rubin, Department of Medicine, Columbia University, New York, NY.
Ian H. de Boer, Department of Medicine, University of Washington, Seattle, WA.
Jye-Yu C. Backlund, The Biostatistics Center, George Washington University, Rockville, MD.
Valerie Arends, Departement of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
Rose Gubitosi-Klug, Case Western Reserve/Rainbow Babies and Children's Hospital, Cleveland, OH.
Amisha Wallia, Northwestern University Feinberg School of Medicine.
Naina Sinha Gregory, Weill Cornell Medical College, New York, NY.
Annette Barnie, University of Toronto, Ontario, Canada.
Andrew J. Burghardt, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
John M. Lachin, The Biostatistics Center, George Washington University, Rockville, MD.
Barbara H. Braffett, The Biostatistics Center, George Washington University, Rockville, MD.
Ann V. Schwartz, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.

Document Type

Journal Article

Publication Date

2-21-2022

Journal

The Journal of clinical endocrinology and metabolism

DOI

10.1210/clinem/dgac099

Keywords

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

Abstract

CONTEXT: Type 1 diabetes (T1D) is characterized by high fracture risk, yet little is known regarding diabetes-related mechanisms or risk factors. OBJECTIVE: Determine if 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 HbA1c; kidney function by estimated glomerular filtration rates (eGFR); 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), 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 (3.8, 10.0), p<0.0001 for each -20 mL/min/1.73 m 2 eGFR), Bone ALP (1.0 U/L (0.2, 1.9), p =0.011), sCTX (53.6 pg/mL (32.6, 74.6), p<0.0001), and TRACP5b (0.3 U/L (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.

APA Citation

Rubin, Mishaela R.; de Boer, Ian H.; Backlund, Jye-Yu C.; Arends, Valerie; Gubitosi-Klug, Rose; Wallia, Amisha; Sinha Gregory, Naina; Barnie, Annette; Burghardt, Andrew J.; Lachin, John M.; Braffett, Barbara H.; and Schwartz, Ann V., "Biochemical Markers of Bone Turnover in Older Adults with Type 1 Diabetes" (2022). GW Authored Works. Paper 129.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/129

Department

Biostatistics and Bioinformatics