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Improving Glycemic Control in T1DM Can Decrease Risk of Fracture

Oct 1, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Amber Satz, PharmD Candidate, LECOM School of Pharmacy

Having type 1 diabetes increases patients’ risk for fracture six-fold, but good blood sugar control can help decrease risk of fracture.

Diabetes has been identified as a risk factor for fragility fractures. The risk of hip fracture is increased about six-fold in patients with type 1 diabetes and about threefold in patients with type 2 diabetes. While many factors contribute to the risk of bone fracture including age at disease onset and use of antidiabetic drugs, the underlying pathophysiology has a major impact on skeletal fragility in both type 1 and type 2 diabetes. As an anabolic hormone, insulin is thought to have a stimulatory effect on osteoblast function. While most patients with type 1 diabetes are diagnosed during childhood, these patients may suffer from a significant decrease in bone mass development during puberty due to insulin deficiency. Also, in type 1 diabetes, rapid bone loss occurs within the first few years of disease onset; it is unclear whether this is due to the decline of insulin secretion or inadequate control of diabetes. In addition, hyperglycemia is associated with diminished bone mineral content, impaired vitamin D and calcium metabolism, and reduced osteoblast activity. On the other hand, type 2 diabetes is associated with normal to increased bone mass but increased cortical porosity is observed. This may be a result of obesity-related insulin resistance and hyperinsulinemia.

Currently, many factors are considered to play a role in the risk of fracture in patients with T1DM and T2DM, including the severity of disease, glucotoxicity, chronic inflammation, and microvascular damage. Also, comorbidities and drug effects that can increase risk of falls are commonly considered to greatly impact risk of fracture. It is currently unclear whether extent of glycemic control has a dose-dependent effect if any on the risk of falls in patients with T1DM or T2DM.

A recent study sought to evaluate the relationship between the degree of glycemic control and the risk of non-vertebral low-trauma fractures in patients with newly diagnosed type 1 and type 2 diabetes. The design of the trial was a nested case-control analysis within the Clinical Practice Research Datalink (CPRD) cohort study including primary care data. Patients with type 2 diabetes (8,859) for at least 3 years or type 1 diabetes (672) for 1 year and incident of low-trauma fracture (non-vertebral fracture) were included. The mean 3-year HaA1c level was 8.7% for patients with T1DM and 7.3% for patients with T2DM. The median interval between diabetes diagnoses and the fracture was 4.5 years for both groups.

Among patients with T1DM, those with poor glycemic control (3-year mean HbA1c >8.0%) had an increased risk of fracture compared to those with good glycemic control (3-year mean HbA1c <7%) with an adjusted odds ratio of 1.39, 95% CI 1.06 to 1.83. Patients with microvascular and macrovascular complications of diabetes including diabetic retinopathy (adjusted OR, 1.29 95% CI, 1.06 to 1.57) and chronic renal failure (adjusted OR 2.24, 95% CI 1.47 to 3.42) had an even further increased fracture risk. 

Among patients with T2DM, glycemic control was not found to be associated with risk of fracture when comparing patients with different ranges of HbA1c values. Unlike the T1DM group, microvascular and macrovascular complications were not found to be clearly associated with fracture risk. The trial did find a major correlation between increased fracture risk and a recent prescription for pioglitazone (OR 1.36, 95% CI 1.25 to 1.49) and rosiglitazone (OR 1.32, 95% CI 1.20 to 1.46) compared with patients with T2DM, not on TZDs. Thiazolidinediones are shown to reduce osteoblast activity and accelerate bone loss; their use is associated with about threefold increased risk of hip and non-vertebral osteoporotic fracture.

Due to the pathophysiological differences between T1DM and T2DM, T1DM is associated with much greater risk for fracture. In the interest of determining whether degree of glycemic control impacts the fracture risk of patients with diabetes, this trial only displayed a correlation between glycemic control and fracture risk in T1DM patients. The lack of correlation within the T2DM group may be attributed to a protective effect of insulin resistance versus insulin deficiency in early disease.

Practice Pearls:

  • Diabetes increases patients’ risk for fracture six-fold in T1DM and three-fold in T2DM.
  • A recent case-control study showed that in T1DM patients, poor glycemic control was associated with an increased fracture risk compared to good glycemic control. 
  • T2DM patients were not found to have any correlation between glycemic control and fracture risk, although microvascular and macrovascular complications increased risk.
  • It is important to counsel patients on the inherently increased risk of fracture due to diabetes, and to even further stress the impact of glycemic control.

Reference for “Improving Glycemic Control in T1DM Can Decrease Risk of Fracture”:


 Amber Satz, PharmD Candidate, LECOM School of Pharmacy