Hyperglycaemia, diabetes and risk of fragility fractures: observational and Mendelian randomisation studies
Authors' conclusion
Hyperglycaemia and diabetes are risk factors for fragility fracture and one- and two-sample MR analyses supported a causal effect of hyperglycaemia on arm fractures. Diabetes and previous fragility fracture jointly conferred the highest risk of death in the general population.
Study context
- Population
- Individuals from the Copenhagen City Heart Study and Copenhagen General Population Study and UK Biobank; MAGIC summary data for two-sample Mendelian Randomisation (MR)117,054 Copenhagen · MAGIC summary data 196,743
- Exposure
- Diabetes vs no diabetes; genetically predicted hyperglycaemia
- Outcome
- Fragility fracture (hip, spine and arm [humerus/wrist]) from national health registries
Methodological detailsone-sample MR, two-sample MR
- One-sample MR
- Two-sample MR
Main finding
As reported in the abstract
Any fragility fracture
Each group vs without diabetesHazard ratio (95% CI)
T1D
1.50(1.19–1.88)
T2D
1.22(1.13–1.32)
- Higher fasting and non-fasting glucose and HbA1c associated with higher risk of any fragility fracture
- P < 0.001
Observational data: associations, not effects.
Further findings
Arm fracture, MR
- One-sample MR, high non-fasting glucose (Copenhagen + UK Biobank), RR
- 1.41 [1.11, 1.79], p=0.004
- Two-sample MR, fasting glucose, OR
- 1.50 [1.03, 2.18], p=0.03
- Two-sample MR, HbA1c, OR
- 2.79 [1.12, 6.93], p=0.03
Any fragility fracture, MR
- One-sample MR, non-fasting glucose
- 1.18 (1.00, 1.41), p=0.06
- Two-sample MR, fasting glucose
- 1.36 (0.89, 2.09), p=0.15
- Two-sample MR, HbA1c
- 2.47 (0.95, 6.43), p=0.06
Cumulative death · age 80 years
- Fragility fracture only
- 27%
- Diabetes only
- 54%
- Both conditions
- 67%
- Neither
- 17%
Original publication
Hyperglycaemia, diabetes and risk of fragility fractures: observational and Mendelian randomisation studies. Diabetologia. Published 14 December 2023. doi:10.
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