Abstract
Objective Type 2 diabetes is associated with an increased risk of fracture. Any factor that incrementally increases this risk should be taken into account when individualising treatment. Hypoglycaemia is a common complication of antidiabetes medications and suggested as a risk factor for fractures; yet, its real-life clinical impact is unclear. Design A population-based, retrospective open cohort study using routinely collected data between 1st of January 1995 and 1st of May 2016 in The Health Improvement Network (THIN) database. Methods Patients with type 2 diabetes mellitus with documented hypoglycaemic events were compared to randomly matched patients with type 2 diabetes mellitus without documented hypoglycaemic events matched to exposed patients on age, sex, duration of diabetes and BMI. The primary outcome was any incident fracture. Secondary outcome was incident fragility (osteoporotic) fracture. Results A total of 41 163 patients with type 2 diabetes were included: 14 147 patients in the exposed cohort and 27 016 patients in the unexposed cohort. Patients with a documented hypoglycaemic event were significantly more likely to sustain any fracture compared to patients with no record of hypoglycaemic events: adjusted IRR = 1.20 (95% CI: 1.12-1.30; P < 0.0001). Patients who had a documented hypoglycaemic event were significantly more likely to suffer a fragility fracture compared to controls: adjusted IRR = 1.24 (95% CI: 1.13-1.37; P < 0.0001). Conclusions Hypoglycaemic events are a significant risk factor for fractures in patients with diabetes mellitus. This observation is clinically relevant when individualising targets for glycaemic control and selecting antidiabetic agents.
Highlights
Each year in the United Kingdom, 1.8 million fractures occur with an annual incidence of about 3.6% and a lifetime prevalence of approximately 40% [1, 2, 3]
Considering that there are 4 million people living with type 2 diabetes mellitus in the United Kingdom, and by 2025, it is estimated that the number will rise to 5 million [10, 11], it is important to further our understanding regarding the underlying risk factors that increase the risk of fractures in type 2 diabetes mellitus patients
A total of 41 163 patients with type 2 diabetes were included in the study population; 14 147 patients were included in the exposed cohort and 27 016 patients were included in the unexposed cohort (Table 1)
Summary
Each year in the United Kingdom, 1.8 million fractures occur with an annual incidence of about 3.6% and a lifetime prevalence of approximately 40% [1, 2, 3]. The annual cost in the United Kingdom for hip fractures alone including medical and social care is about £2 billion [4]. Despite their apparently normal areal bone density, patients with type 2 diabetes mellitus have an increased risk of fragility (osteoporotic) fractures [5, 6, 7, 8, 9]. Patients with type 2 diabetes mellitus may be at an increased risk of falls, as a result of concomitant medications (such as antihypertensive treatment), peripheral neuropathy due to diabetes and associated impaired mechano-sensation, orthostatic hypotension caused by autonomic neuropathy and possibly hypoglycaemic events associated with antihyperglycaemic therapy. Considering that there are 4 million people living with type 2 diabetes mellitus in the United Kingdom, and by 2025, it is estimated that the number will rise to 5 million [10, 11], it is important to further our understanding regarding the underlying risk factors that increase the risk of fractures in type 2 diabetes mellitus patients
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