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. 2024 Jul 25:15:1404747.
doi: 10.3389/fendo.2024.1404747. eCollection 2024.

Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis

Qifan Yang  1 , Xinyu Wang  1 , Yanwei Liu  1 , Jing Liu  2 , Dong Zhu  1
Affiliations

Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis

Qifan Yang et al. Front Endocrinol (Lausanne). .

Abstract

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role.

Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship.

Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship.

Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.

Keywords: Mendelian randomization; OS; T2DM; osteoporosis; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
MR study design. Stage I: MR analysis of T2DM and OS samples was performed. Stage 2: to explore the potential role of obesity indicators and mediating variables in causality. MR, Mendelian randomization; T2DM, type 2 diabetes mellitus; OS, osteoporosis.
Figure 2
Figure 2
T2DM can induce changes in inflammatory factors and osteogenic proteins. (A) Western blotting: palmitic acid decreases the expression of osteogenic proteins and increases the expression of inflammatory factors. (B) Alkaline phosphatase staining: osteoblasts were treated with palmitic acid, and their osteogenic differentiation ability decreased. T2DM, type 2 diabetes mellitus.
Figure 3
Figure 3
The scatter plots: causal relationship between T2DM and OS. (A) Osteoporosis. (B) Osteoporosis (U KB-B-17796). T2DM, type 2 diabetes mellitus; OS, osteoporosis.
Figure 4
Figure 4
The forest plot: causal relationship between T2DM and OS. (A) Osteoporosis (finn-b-M13_OSTEOPOROSIS). (B) Osteoporosis (UKB-B-1 7796). T2DM, type 2 diabetes mellitus; OS, osteoporosis.
Figure 5
Figure 5
The funnel plot: causal relationship between T2DM and OS. (A) Osteoporosis. (B) Osteoporosis (UKB-B-17796). T2DM, type 2 diabetes mellitus; OS, osteoporosis.
Figure 6
Figure 6
The forest plots. (A) The forest plot of the causal relationship between T2DM and OS. (B) The forest plot of MVMR results. T2DM, type 2 diabetes mellitus; OS, osteoporosis; MVMR, multivariable Mendelian randomization.
See this image and copyright information in PMC

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