Biochemical Markers of BoneTurnover in Older Adults With Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2022-06, Vol.107 (6), p.e2405
• Main Authors: Rubin, Mishaela R, de Boer, Ian H, Backlund, Jye-Yu C, Arends, Valerie, Gubitosi-Klug, Rose, Wallia, Amisha, Gregory, Naina Sinha, Barnie, Annette, Burghardt, Andrew J, Lachin, John M, Braffett, Barbara H, Schwartz, Ann V
• Format: Article
• Language: English
• Subjects: Care and treatment; Diabetes therapy; Diabetic retinopathy; Epidemiology; Ethylenediaminetetraacetic acid; Glycosylated hemoglobin; Phosphatases; Risk factors; Skin; Type 1 diabetes
• ISSN: 0021-972X
• DOI: 10.1210/clinem/dgac099

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 olderT 1 D adults. Design: Cross-sectional Setting: Epidemiology of Diabetes Interventions and Complications study (6 of 27 clinical centers) Participants: 232 T1 D 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 [+ or -] 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 [(5 -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 [m.sup.2] 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], andTRACP5b [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. HbA1 c, eGFR, and AGEs were not associated with sclerostin levels Conclusions: Among older adults withTI D, 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: bone turnover markers, skin intrinsic fluorescence, advanced glycation end products, estimated glomerular filtration rates, proliferative diabetic retinopathy, diabetic peripheral neuropathy