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

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 \u3e30 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\u3c0.0001 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\u3c0.0001), 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

Risk factors for lower bone mineral density in older adults with type 1 diabetes: a cross-sectional study

BACKGROUND: Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes. METHODS: This cross-sectional study was embedded in a long-term observational study, the Epidemiology of Diabetes Interventions and Complications study (EDIC), a cohort of participants with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and Canada. All active EDIC participants were eligible except if they were pregnant, weighed above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator, or were not willing to participate. The primary study outcome was total hip BMD. Hip, spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an annual EDIC visit (2017-19). Time-weighted mean HbA, kidney disease, and peripheral neuropathy were measured annually during EDIC, and retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed once (2009-10) during EDIC. FINDINGS: 1147 of the 1441 participants who were enrolled in the DCCT trial remained active EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017, and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health study. 1058 participants completed at least one of a set of DXA scans and were included in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7). Higher mean HbA, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy) were independently associated with a lower total hip BMD. Total hip BMD differed by -10·7 mg/cm (95% CI -19·6 to -1·7) for each 1% increase in mean HbA, -20·5 mg/cm (-29·9 to -11·0) for each 5 unit higher skin intrinsic fluorescence, and -51·7 mg/cm (-80·6 to -22·7) in the presence of kidney disease. Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS. INTERPRETATION: Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic control and prevention of kidney disease might reduce bone loss and ultimately fractures in this population. Osteoporosis screening might be particularly important in people with these risk factors. Further research to identify AGE blockers could benefit skeletal health. FUNDING: National Institute of Diabetes and Digestive and Kidney Disease