Poor Glycemic Control Is Associated With Impaired Bone Accrual in the Year Following a Diagnosis of Type 1 Diabetes

Abstract

Context Type 1 diabetes (T1D) is associated with an increased fracture risk across the life course. The effects on bone accrual early in the disease are unknown. Objective To characterize changes in bone density and structure over the year following diagnosis of T1D and to identify contributors to impaired bone accrual. Design Prospective cohort study. Setting Academic children’s hospital. Participants Thirty-six children, ages 7 to 17 years, enrolled at diagnosis of T1D. Outcomes Whole body and regional dual-energy X-ray absorptiometry and tibia peripheral quantitative computed tomography obtained at baseline and 12 months. The primary outcome was bone accrual assessed by bone mineral content (BMC) and areal bone mineral density (aBMD) velocity z score. Results Participants had low total body less head (TBLH) BMC (z = −0.46 ± 0.76), femoral neck aBMD (z = −0.57 ± 0.99), and tibia cortical volumetric BMD (z = −0.44 ± 1.11) at diagnosis, compared with reference data, P < 0.05. TBLH BMC velocity in the year following diagnosis was lower in participants with poor (hemoglobin A1c ≥7.5%) vs good (hemoglobin A1c <7.5%) glycemic control at 12 months, z = −0.36 ± 0.84 vs 0.58 ± 0.71, P = 0.003. TBLH BMC velocity was correlated with gains in tibia cortical area (R = 0.71, P = 0.003) and periosteal circumference (R = 0.67, P = 0.007) z scores in participants with good, but not poor control. Conclusions Our results suggest that the adverse effects of T1D on BMD develop early in the disease. Bone accrual following diagnosis was impaired in participants with poor glycemic control and appeared to be mediated by diminished bone formation on the periosteal surface.

<p>Type 1 Diabetes and Bone Fragility: Links and Risks</p>

“…Hence, changes may occur early in T1D as children with T1D have decreased fn BMD with a Z-score of −0.57, similar to previously described meta-analysis 13,18,19. In addition, children with T1D and glycated hemoglobin A1c (HbA1c) ≥7.5% have lower bone mass accrual during twelve months18 and adolescents with T1D and HbA1c ≥8.0% have lower total body BMD compared to those with better glycemic control 20. The early onset of low BMD in T1D may be due to calcium loss, as 25% of young women with T1D had greater urinary calcium excretion and less calcium retention in a study that used a dual stable calcium isotope to evaluate calcium intake and excretion 21.…”

“…Likewise, Hamilton et al followed 48 patients with T1D for 10 years and found that BMD at the spine, fn, and forearm remained stable when adjusted for body mass index (BMI) 17. Hence, changes may occur early in T1D as children with T1D have decreased fn BMD with a Z-score of −0.57, similar to previously described meta-analysis 13,18,19. In addition, children with T1D and glycated hemoglobin A1c (HbA1c) ≥7.5% have lower bone mass accrual during twelve months18 and adolescents with T1D and HbA1c ≥8.0% have lower total body BMD compared to those with better glycemic control 20.…”

Impact of Diabetes Mellitus on Bone Health

“…Both the lack of insulin, among other pancreatic anabolic hormones, and low IGF1 levels suppress the terminal differentiation of mesenchymal stem cells (MSCs) into osteoblasts in addition to osteoblastic activity [11]. Therefore, this inhibits skeletal growth at a young age, which leads to an inadequate accrual of peak bone mass [12,13,14,15,16]. On the contrary, T2DM affects bone health in advanced stages of the disease where many factors such as insulinopenia, hyperglycemia, the development of advanced glycation end products (AGEs), chronic inflammation, and microvascular disease coincide to negatively affect bone architecture and biomechanical properties of the bone (Figure 1) [17,18].…”

Management of fracture risk in patients with diabetes—Chinese Expert Consensus

“…Although strict glycemic control does not necessarily reduce the risk of fractures, several studies have indicated that poor glycemic control (HbA1c ≥8%–9%) increases fracture risk compared with standard control in T1D and T2D, and that bone accrual following the diagnosis of T1D was impaired in individuals with poor glycemic control . Thus, for patients with diabetes, glycemic control remains a top priority, and the decrease in blood glucose level should be smooth to prevent hypoglycemia and its consequences, including fracture …”