Poor Glycemic Control Increases Fracture Risk in T1D

woman with fracture cast
woman with fracture cast
Poor glycemic control in patients with newly diagnosed type 1 diabetes, but not type 2 diabetes, was associated with an increased risk for low-trauma fracture.

Poor glycemic control in patients with newly diagnosed type 1 diabetes (T1D) was associated with an increased risk for low-trauma fracture, according to study results published in The Journal of Clinical Endocrinology & Metabolism. Glycemic levels in patients with newly diagnosed type 2 diabetes (T2D) were not associated with risk for fracture, but the use of certain antidiabetic medications was.

The investigators of this nested case-control study sought to examine the impact of glycemic control on the risk for nonvertebral low-trauma fractures in patients newly diagnosed with T1D and T2D.

The study population included individuals newly diagnosed with T1D (n = 3329) and T2D (n = 44,275) who had onset of diabetes between 1995 and 2015. For each patient who had a recorded low-trauma fracture, 4 controls were matched for age ± 3 years, sex, fracture index date, diabetes type, and diabetes duration ± 1 year. The primary outcome measure of interest was glycemic control defined by hemoglobin A1c (HbA1c) levels after diabetes onset. 

Conditional logistic regression models were used to assess the association between HbA1c values and fracture risk; analyses were adjusted for potentially confounding variables, including body mass index, smoking status, complications related to diabetes, and antidiabetic medications.

For both T1D and T2D, the median duration between diabetes onset and fracture date was 4.5 years. For T1D, patients with poor glycemic control (3-year mean HbA1c levels >8.0%) had an increased risk for fracture (adjusted odds ratio [aOR,] 1.39; 95% CI, 1.06-1.83) compared with patients with moderate (3-year mean HbA1c levels >7.0% to 8.0%) or good glycemic control (3-year mean HbA1c levels ≤7.0%). Glycemic control did not affect the risk for fracture in patients with T2D. However, independent from glycemic control, participants with T2D reporting current rosiglitazone use (aOR, 1.32; 95% CI, 1.20-1.46) or pioglitazone use (aOR, 1.36; 95% CI, 1.25-1.49) had an increased risk for fracture compared with nonusers.

A limitation of the study included a higher proportion of participants with T2D who demonstrated good glycemic control relative to other studies. In addition, the cause of fracture was mostly unknown, and because fractures risk is associated with several comorbidities and drugs, residual confounding may have been present. Possible misclassification of T1D or T2D or of disease onset may also have affected study outcomes.

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Overall, poor glycemic control was associated with increased risk for fracture in T1D but not in T2D, suggesting insulin resistance has a protective effect early in the disease.

“Current use of rosiglitazone and pioglitazone was associated with an increased risk [for] fracture in our study independent of glycemic control,” wrote the researchers. “Preclinical and clinical studies indicated that thiazolidinediones adversely affect bone metabolism, resulting in reduced osteoblastic bone formation and accelerated bone loss, and thus may increase fracture risk.”

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Vavanikunnel J, Charlier S, Becker C, et al. Association between glycemic control and risk of fracture in diabetic patients: A nested case-control study [published online January 16, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01879