Elevated HbA1c Is Associated with Altered Cortical and Trabecular Microarchitecture in Girls with Type 1 Diabetes

Abstract

Context: Skeletal fragility is a significant complication of type 1 diabetes (T1D), with an increased risk of fracture observed starting in childhood. Altered bone accrual and microarchitectural development during the critical peripubertal years may contribute to this fragility.

Objective: To evaluate differences in skeletal microarchitecture between girls with T1D and controls and to assess factors associated with these differences.

Design: Cross-sectional comparison.

Participants: Girls ages 10-16 years, 62 with T1D and 61 controls.

Results: Areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry did not differ between girls with and without T1D. At the distal tibia, trabecular BMD was 7.3 ± 2.9% lower in T1D (P = 0.013), with fewer plate-like and axially-aligned trabeculae. Cortical porosity was 21.5 ± 10.5% higher, while the estimated failure load was 4.7 ± 2.2% lower in T1D (P = 0.043 and P = 0.037, respectively). At the distal radius, BMD and microarchitecture showed similar differences between the groups but did not reach statistical significance. After stratifying by HbA1c, only those girls with T1D and HbA1c > 8.5% differed significantly from controls. P1NP, a marker of bone formation, was lower in T1D while CTX and TRAcP5b, markers of bone resorption and osteoclast number, respectively, did not differ. The insulin-like growth factor 1 (IGF-1) Z-score was lower in T1D, and after adjustment for the IGF-1 Z-score, associations between T1D status and trabecular microarchitecture were largely attenuated.

Conclusions: Skeletal microarchitecture is altered in T1D early in the course of disease and among those with higher average glycemia. Suppressed bone formation and lower circulating IGF-1 likely contribute to this phenotype.

Trial registration: ClinicalTrials.gov NCT02140424.

Keywords: bone density; microarchitecture; pediatrics; type 1 diabetes.

Figure 1.

Percent differences in volumetric bone mineral density, microarchitecture, and estimated failure load at the distal radius (gray bars) and tibia (black bars) between T1D and control subjects. Percent differences are adjusted for bone age, height, and weight, and error bars represent standard error of marginal effect. Abbreviations: Cort, cortical; BMD, bone mineral density; BV/TV, bone volume over total volume; Junc D, junction density; L, length; N, number; Po, porosity; PP, plate-plate; RP, rod-plate; RR, rod-rod; SA, surface area; Sp, spacing; Trab, trabecular; Th, thickness. *P < 0.05 compared to control subjects.

Figure 2.

Least square mean estimates of volumetric bone mineral density, microarchitecture, and estimated failure load at the distal radius and tibia in control (open bar), T1D-low (gray bars), and T1D-high (black bars) subjects. Means adjusted for bone age, height, and weight. Error bars represent standard error of the marginal effect.

Figure 3.

Least square mean estimates of bone turnover markers in control (open bar), T1D-low (gray bars), and T1D-high (black bars) subjects. Means adjusted for bone age. Error bars represent standard error of the marginal effect.