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

Document Type

Journal Article

Publication Date



The Journal of clinical endocrinology and metabolism




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


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.


Biostatistics and Bioinformatics