Aside from many other health problems related to diabetes, an increased risk of bone fractures has recently been recognised as another possible complication. The risk of fracture has been reported to be higher among patients with type-1-diabetes than with type-2-diabetes, and was observed in men and women.
However, only few studies on this topic have focussed on the impact of blood sugar control by analysing the patient's HbA1c-values; HbA1c-values represent the amount of red blood cells to which sugar (scientifically "glucose") is bound and transported in the blood. The amount of bounded glucose is an indicator for mean blood glucose concentration within the previous 8 weeks and therefore an important marker of diabetes control.
It is unclear, how antidiabetic drugs and HbA1c-values are associated with the risk of fractures.
Only two previous studies which examined the association between HbA1c-values and fractures included substantial numbers of patients, while other studies were small. To our knowledge there is no study that analysed the risk of fracture associated with use of antidiabetic drugs according to HbA1c-levels, considering also the timing and duration of drug use.
In our large study we will explore the association between diabetes control (blood sugar level, HbA1c value), and the fracture risk in patients with diabetes type 1 or type 2 according to their antidiabetic medication and medication scheme. This would help answer the question whether good diabetes control could prevent fractures in diabetes patients in accordance with their diabetes medication, an important piece of information for both patients and GPs.
We will conduct a follow-up study followed by a 1:4 matched nested case-control analysis in diabetes patients (type 1 or 2) to explore the association between diabetes control (based on HbA1c-levels), diabetes duration, and the risk of low-trauma fractures. In an additional analysis, the association between diabetes medication/medication scheme will be assessed in combination with the diabetes control on the risk of fractures.
Cohort study:
We will identify a cohort of newly diagnosed diabetes patients within the study period (01.01.1995 - 31.12.2015). Patients with type 1 or 2 diabetes must have >3 years of history in the database before their first diabetes code, respectively. We will follow the DM patients until they experience a low-trauma fracture. The time from diabetes diagnose to fracture will be analysed for various categories of HbA1c-levels. The goal of this analysis is to quantify the fracture risk in relation to diabetes duration.
Nested case control analysis:
Each diabetes patient who experienced a low-trauma fracture after the diabetes diagnosis will be matched to 4 diabetes patients with no recorded fracture. Cases and controls will be matched on age, sex, general practice, index date, diabetes type, and diabetes duration (follow-up time between diabetes onset and fracture date) by risk set sampling. For our additional analysis on the risk of fractures according to diabetes control and diabetes medication/medication schemes (timing and duration of drug use), only type 2 diabetes patients will be analysed. In this additional study we will match on age, sex, general practice, and index date by risk set sampling, but not on diabetes duration. Patients for the additional analysis are also required to have >3 years of history in the database before their first diabetes code.
The goal of this analysis is to examine the association between diabetes control and the risk of fracture. Medication prescribed to diabetes type 2 patients will additionally be taken into account to assess this association in the mentioned additional analysis.
We will perform statistical analysis with SAS version 9.4.
Non-traumatic fractures in diabetes patients.
Christoph Meier - Chief Investigator - University of Basel
Claudia Becker - Corresponding Applicant - University of Basel
Christian Meier - Collaborator - University of Basel
Janina Vavanikunnel - Collaborator - University of Basel
Sarah Charlier - Collaborator - University of Basel
Susan Jick - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program