Association between glycaemic control and fracture risk in diabetic patients: a nested case control study

Introduction:

Diabetes is associated with an increased risk of non-vertebral fractures in both, type 1 (T1DM) and type 2 diabetes (T2DM). Pathophysiological mechanisms contributing to skeletal fragility are multifactorial and differ between diabetes types. We aimed to evaluate the association between diabetes control and the risk of low-trauma fractures since the impact of glycaemic control on fracture risk remains unclear.

Methods:

We conducted a nested case-control study within a cohort of patients with incident T1DM or T2DM between 1995 and 2015 based on the UK-based Clinical Practice Research Datalink. We identified all patients with a low-trauma fracture after the diabetes diagnosis. Using risk-set sampling, we matched them to 4 diabetes patients with no recorded fracture, matching on age, sex, general practice, index date, diabetes type, and diabetes duration (follow-up time between diabetes onset and fracture date). We characterized the study population with regard to comedications and comorbidities, and used conditional logistic regression analyses to assess the association between diabetes control (based on HbA1c-levels) and the risk of low-trauma fractures. We calculated crude and adjusted odds ratios (aOR), adjusting for BMI and smoking, as well as for specific diabetes complications and medications.

Results:

We identified 566 T1DM cases and 2225 T1DM matched controls, as well as 8859 T2DM cases and 35416 T2DM matched controls. T1DM and T2DM patients had a mean of 8.5 (SD 8.4) and 11.1 (SD 9.6) recorded HbA1c-values, and median disease duration of 4.2 years (Q1 1.9, Q3 7.6) and 4.5 years (Q1 2.0, Q3 7.9), respectively. In T1DM patients with a 3- year mean HbA1c > 8.0%, fracture risk was significantly increased (aOR 1.46; 95%CI, 1.09 – 1.97) compared to T1DM patients with HbA1c-levels < 8.0%. In T2DM patients with mean HbA1c-levels of 8 – 9% and > 9%, aORs were 0.91 (95%CI, 0.84 – 0.99) and 0.96 (95%CI, 0.88 – 1.06), showing no elevated fracture risk compared to HbA1c-levels < 8.0%. Comorbidities associated with micro- and macrovascular complications of diabetes, such as diabetic retinopathy, chronic renal failure, and coronary heart failure, were all associated with an elevated fracture risk

Discussion:

The impact of glycaemic control on low-trauma fracture risk differs in T1DM and T2DM patients with short term disease. While poor glycaemic control (HbA1c levels > 8%) elevated the fracture risk in T1DM patients no such association was observed in T2DM. This could be attributed to a protective effect of insulin resistance in early disease. Further studies are needed to evaluate other factors related to fracture risk in T2DM (e.g. disease duration or comorbidities).