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

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....

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Autores principales: Mitchell, Adam, Larsson, Susanna C., Fall, Tove, Melhus, Håkan, Michaëlsson, Karl, Byberg, Liisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099809/
https://www.ncbi.nlm.nih.gov/pubmed/33650017
http://dx.doi.org/10.1007/s00125-021-05410-w
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author Mitchell, Adam
Larsson, Susanna C.
Fall, Tove
Melhus, Håkan
Michaëlsson, Karl
Byberg, Liisa
author_facet Mitchell, Adam
Larsson, Susanna C.
Fall, Tove
Melhus, Håkan
Michaëlsson, Karl
Byberg, Liisa
author_sort Mitchell, Adam
collection PubMed
description 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 cm(2) [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/cm(2) [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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05410-w.
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spelling pubmed-80998092021-05-11 Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study Mitchell, Adam Larsson, Susanna C. Fall, Tove Melhus, Håkan Michaëlsson, Karl Byberg, Liisa Diabetologia Article 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 cm(2) [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/cm(2) [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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05410-w. Springer Berlin Heidelberg 2021-03-02 2021 /pmc/articles/PMC8099809/ /pubmed/33650017 http://dx.doi.org/10.1007/s00125-021-05410-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Mitchell, Adam
Larsson, Susanna C.
Fall, Tove
Melhus, Håkan
Michaëlsson, Karl
Byberg, Liisa
Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title_full Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title_fullStr Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title_full_unstemmed Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title_short Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study
title_sort fasting glucose, bone area and bone mineral density: a mendelian randomisation study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099809/
https://www.ncbi.nlm.nih.gov/pubmed/33650017
http://dx.doi.org/10.1007/s00125-021-05410-w
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