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. 2022 May 17;107(6):e2405-e2416.
doi: 10.1210/clinem/dgac099.

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

Mishaela R Rubin  1 , Ian H de Boer  2 , Jye-Yu C Backlund  3 , Valerie Arends  4 , Rose Gubitosi-Klug  5 , Amisha Wallia  6 , Naina Sinha Gregory  7 , Annette Barnie  8 , Andrew J Burghardt  9 , John M Lachin  3 , Barbara H Braffett  3 , Ann V Schwartz  10
Affiliations

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

Mishaela R Rubin et al. J Clin Endocrinol Metab. .

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 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.

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

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Figures

Figure 1.
Figure 1.
Bone biomarkers flow chart in EDIC participants and controls at six clinics.
See this image and copyright information in PMC

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