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Diabetes Risk Factors and Bone Microarchitecture as Assessed by High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Adults with Long-standing Type 1 Diabetes

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posted on 2023-11-29, 22:42 authored by Naina Sinha Gregory, Andrew J. Burghardt, Jye-Yu C. Backlund, Mishaela R. Rubin, Ionut Bebu, Barbara H. Braffett, David J. Kenny, Thomas M. Linker, Galateia J. Kazakia, Annette Barnie, John M. Lachin, Rose Gubitosi-Klug, Ian H de Boer, Ann V. Schwartz

Objective: To determine whether type 1 diabetes and its complications are associated with bone geometry and microarchitecture.

Research Design and Methods: Cross-sectional study embedded in a long-term observational study. High-resolution peripheral quantitative computed tomography (HR-pQCT) scans of distal radius and distal and diaphyseal tibia were performed in a subset of 183 type 1 diabetes participants from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and 94 controls without diabetes. HbA1c, skin advanced glycation end products (AGEs), and diabetes-related complications were assessed in EDIC participants with >30 years of follow-up.

Results: Compared to controls (60±8 years-old, 65% female), EDIC participants (60±7 years-old, diabetes duration 38±5 years, 51% female) had lower total bone mineral density (BMD) at distal radius (-7.9%, 95%CI:(-15.2%,-0.6%), p=0.030) and distal tibia (-11.3%, 95%CI:(-18.5%,-4.2%), p=0.001); larger total area at all sites (distal radius +4.7%, 95%CI:(+0.5%,+8.8%), p=0.030; distal tibia +5.9%, 95%CI:(+2.1%,+9.8%), p=0.003; diaphyseal tibia +3.4%, 95%CI (+0.8%,+6.1%), p=0.011); and poorer radius trabecular and cortical microarchitecture. Estimated failure load was similar between two groups. Among EDIC, higher HbA1c, AGE and macroalbuminuria were associated with lower total BMD. Macroalbuminuria was associated with larger total area and lower cortical thickness at distal radius. Higher HbA1c and AGE, lower glomerular filtration rate, peripheral neuropathy and retinopathy were associated with deficits in trabecular microarchitecture.

Conclusions: Type 1 diabetes is associated with lower BMD, larger bone area and poorer trabecular microarchitecture. Among 1 diabetes, suboptimal glycemic control, AGE accumulation and microvascular complications are associated with deficits in bone microarchitecture and lower BMD.

Funding

The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK; current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA. The sponsor of this study is represented by the NIDDK Project Scientist who serves as part of the DCCT/EDIC Research Group and plays a part in the study design and conduct as well as the review and approval of manuscripts. The NIDDK Project Scientist was not a member of the writing group of this paper. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies.

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