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
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.