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Published in: Journal of Bone and Mineral Metabolism 1/2024

29-12-2023 | Insulins | Original Article

Causal relationship between glycemic traits and bone mineral density in different age groups and skeletal sites: a Mendelian randomization analysis

Authors: Zhangmeng Xu, Yushan Shi, Changhong Wei, Tao Li, Jiang Wen, Wanli Du, Yaming Yu, Tianmin Zhu

Published in: Journal of Bone and Mineral Metabolism | Issue 1/2024

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Abstract

Introduction

Previous research has confirmed that patients with type 2 diabetes mellitus tend to have higher bone mineral density (BMD), but it is unknown whether this pattern holds true for individuals without diabetes. This Mendelian randomization (MR) study aims to investigate the potential causal relationship between various glycemic trait (including fasting glucose, fasting insulin, 2-h postprandial glucose, and glycated hemoglobin) and BMD in non-diabetic individuals. The investigation focuses on different age groups (15–30, 30–45, 45–60, and 60 + years) and various skeletal sites (forearm, lumbar spine, and hip).

Materials and methods

We utilized genome-wide association study data from large population-based cohorts to identify robust instrumental variables for each glycemic traits parameter. Our primary analysis employed the inverse-variance weighted method, with sensitivity analyses conducted using MR-Egger, weighted median, MR-PRESSO, and multivariable MR methods to assess the robustness and potential horizontal pleiotropy of the study results.

Results

Fasting insulin showed a negative modulating relationship on both lumbar spine and forearm. However, these associations were only nominally significant. No significant causal association was observed between blood glucose traits and BMD across the different age groups. The direction of fasting insulin’s causal effects on BMD showed inconsistency between genders, with potentially decreased BMD in women with high fasting insulin levels and an increasing trend in BMD in men.

Conclusions

In the non-diabetic population, currently available evidence does not support a causal relationship between glycemic traits and BMD. However, further investigation is warranted considering the observed gender differences.
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Literature
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Metadata
Title
Causal relationship between glycemic traits and bone mineral density in different age groups and skeletal sites: a Mendelian randomization analysis
Authors
Zhangmeng Xu
Yushan Shi
Changhong Wei
Tao Li
Jiang Wen
Wanli Du
Yaming Yu
Tianmin Zhu
Publication date
29-12-2023
Publisher
Springer Nature Singapore
Keywords
Insulins
Insulins
Published in
Journal of Bone and Mineral Metabolism / Issue 1/2024
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-023-01480-5

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