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不同年龄组和骨骼部位血糖特征与骨密度之间的因果关系:孟德尔随机化分析

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

作者信息

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

机构信息

Department of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, No. 37 Shi-er-qiao Road, Chengdu, Sichuan, China.

Department-2 of Neck Shoulder Back and Leg Pain, Department of Preventive Treatment, Sichuan Province Orthopaedic Hospital, Chengdu, Sichuan, China.

出版信息

J Bone Miner Metab. 2024 Jan;42(1):90-98. doi: 10.1007/s00774-023-01480-5. Epub 2023 Dec 29.


DOI:10.1007/s00774-023-01480-5
PMID:38157037
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.

摘要

引言:先前的研究已证实2型糖尿病患者往往具有较高的骨密度(BMD),但尚不清楚这种模式在无糖尿病个体中是否成立。这项孟德尔随机化(MR)研究旨在调查非糖尿病个体中各种血糖性状(包括空腹血糖、空腹胰岛素、餐后2小时血糖和糖化血红蛋白)与骨密度之间的潜在因果关系。研究重点关注不同年龄组(15 - 30岁、30 - 45岁、45 - 60岁和60岁以上)以及不同骨骼部位(前臂、腰椎和髋部)。 材料与方法:我们利用来自大型人群队列的全基因组关联研究数据,为每个血糖性状参数确定稳健的工具变量。我们的主要分析采用逆方差加权法,并使用MR-Egger、加权中位数、MR-PRESSO和多变量MR方法进行敏感性分析,以评估研究结果的稳健性和潜在的水平多效性。 结果:空腹胰岛素对腰椎和前臂均显示出负向调节关系。然而,这些关联仅在名义上具有显著性。在不同年龄组中,未观察到血糖性状与骨密度之间存在显著的因果关联。空腹胰岛素对骨密度的因果效应方向在性别之间存在不一致,空腹胰岛素水平高的女性骨密度可能降低,而男性骨密度有增加趋势。 结论:在非糖尿病人群中,现有证据不支持血糖性状与骨密度之间存在因果关系。然而,考虑到观察到的性别差异,有必要进行进一步研究。

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

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[6]
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[7]
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本文引用的文献

[1]
Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies.

Front Immunol. 2023

[2]
In osteoporosis or osteopenia, exercise interventions improve BMD; effects vary by exercise type and BMD site.

Ann Intern Med. 2022-4

[3]
Age-Related Changes in Bone Density, Microarchitecture, and Strength in Postmenopausal Black and White Women: The SWAN Longitudinal HR-pQCT Study.

J Bone Miner Res. 2022-1

[4]
The trans-ancestral genomic architecture of glycemic traits.

Nat Genet. 2021-6

[5]
Is diabetes mellitus a risk factor for low bone density: a systematic review and meta-analysis.

BMC Endocr Disord. 2021-4-13

[6]
Population Vitamin D Stores Are Increasing in Tasmania, and This Is Associated With Less BMD Loss Over 10 Years.

J Clin Endocrinol Metab. 2021-7-13

[7]
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Nat Commun. 2021-1-5

[8]
Impact of Type 2 Diabetes Mellitus and Antidiabetic Medications on Bone Metabolism.

Curr Diab Rep. 2020-11-27

[9]
Glycemic traits and Alzheimer's disease: a Mendelian randomization study.

Aging (Albany NY). 2020-11-16

[10]
Bone Regulation of Insulin Secretion and Glucose Homeostasis.

Endocrinology. 2020-10-1

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