Effect of type 2 diabetes mellitus on bone mineral density in different age groups:a two-sample Mendelian randomization study

ABSTRACT

BACKGROUND:

Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown.

To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique.

The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.The βvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages. RESULTS AND

A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with ageage-unspecified bone mineral density[β=0.038,95%confidence interval(CI)1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI0.96-1.04,P=0.716).Similar results were obtained from the MR-Egger regression and weighted median estimator analyses.These findings indicate that type 2 diabetes mellitus may be one of the protective factors of bone mineral density,and there is a correlation with age.