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Fasting glucose, bone area and bone mineral density: A Mendelian randomisation study.

Mitchell, Adam LU ; Larsson, Susanna ; Fall, Tove ; Melhus, Håkan ; Michaëlsson, Karl and Byberg, Liisa (2021) In Diabetologia 64. p.1348-1357
Abstract
Aims/hypothesis
Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.

Methods
We selected 35 SNPs strongly associated with fasting glucose (p < 5 × 10−8) in a non-diabetic European-descent population from the... (More)
Aims/hypothesis
Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.

Methods
We selected 35 SNPs strongly associated with fasting glucose (p < 5 × 10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors and Uppsala Longitudinal Study of Adult Men.

Results
In a meta-analysis of the three cohorts, a genetically predicted 1 mmol/l increment of fasting glucose was associated with a 2% smaller total hip bone area (−0.67 cm2 [95% CI −1.30, −0.03; p = 0.039]), yet was also associated, albeit without reaching statistical significance, with a 4% higher total hip BMD (0.040 g/cm2 [95% CI −0.00, 0.07; p = 0.060]).

Conclusions/interpretation
Fasting glucose may be a causal risk factor for smaller bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings. (Less)
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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Diabetologia
volume
64
pages
1348 - 1357
publisher
Springer
external identifiers
  • scopus:85101906698
ISSN
1432-0428
DOI
10.1007/s00125-021-05410-w
language
English
LU publication?
no
id
75d26d58-a67b-423d-9352-218b79e8b8a1
date added to LUP
2025-02-07 10:39:24
date last changed
2025-02-08 04:01:56
@article{75d26d58-a67b-423d-9352-218b79e8b8a1,
  abstract     = {{Aims/hypothesis<br/>Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.<br/><br/>Methods<br/>We selected 35 SNPs strongly associated with fasting glucose (p &lt; 5 × 10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors and Uppsala Longitudinal Study of Adult Men.<br/><br/>Results<br/>In a meta-analysis of the three cohorts, a genetically predicted 1 mmol/l increment of fasting glucose was associated with a 2% smaller total hip bone area (−0.67 cm2 [95% CI −1.30, −0.03; p = 0.039]), yet was also associated, albeit without reaching statistical significance, with a 4% higher total hip BMD (0.040 g/cm2 [95% CI −0.00, 0.07; p = 0.060]).<br/><br/>Conclusions/interpretation<br/>Fasting glucose may be a causal risk factor for smaller bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings.}},
  author       = {{Mitchell, Adam and Larsson, Susanna and Fall, Tove and Melhus, Håkan and Michaëlsson, Karl and Byberg, Liisa}},
  issn         = {{1432-0428}},
  language     = {{eng}},
  pages        = {{1348--1357}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Fasting glucose, bone area and bone mineral density: A Mendelian randomisation study.}},
  url          = {{http://dx.doi.org/10.1007/s00125-021-05410-w}},
  doi          = {{10.1007/s00125-021-05410-w}},
  volume       = {{64}},
  year         = {{2021}},
}