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

被引:21
作者
Mitchell, Adam [1 ]
Larsson, Susanna C. [1 ]
Fall, Tove [2 ]
Melhus, Hakan [3 ]
Michaelsson, Karl [1 ]
Byberg, Liisa [1 ]
机构
[1] Uppsala Univ, Dept Surg Sci, Orthopaed, Uppsala, Sweden
[2] Uppsala Univ, Dept Med Sci, Mol Epidemiol, Uppsala, Sweden
[3] Uppsala Univ, Dept Med Sci Clin Pharmacogen & Osteoporosis, Uppsala, Sweden
基金
瑞典研究理事会;
关键词
Bone area; Bone mineral density; Fasting glucose; Mendelian randomisation; Single nucleotide polymorphisms;
D O I
10.1007/s00125-021-05410-w
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 x 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.
引用
收藏
页码:1348 / 1357
页数:10
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