吸烟的代谢概况,与2型糖尿病的关联以及与遗传易感性相互作用
Yuxia Wei1, Sara Hägg2, Jonathan K L Mak2,3
1Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Stockholm, 17177, Sweden. yuxia.wei@ki.se.
吸烟显著增加了2型糖尿病 (T2D) 的风险,代谢变化调解了这一效应. 遗传易感性放大了这些代谢变化对T2D发展的影响.
科学领域:
- 代谢学 代谢学 代谢学
- 流行病学 流行病学
- 遗传学 是一个遗传学.
背景情况:
- 吸烟者患2型糖尿病 (T2D) 的风险更高,但确切的生物机制仍然难以捉摸.
- 这项研究调查了代谢变化的作用,作为吸烟和T2D之间的关联中介.
- 这项研究还研究了吸烟引起的代谢变化和对糖尿病和胰岛素抵抗的遗传倾向之间的潜在相互作用.
研究的目的:
- 为了确定与吸烟相关的特定代谢物.
- 为了确定这些与吸烟相关的代谢变化是否会导致T2D的风险增加.
- 评估是否对T2D或胰岛素抵抗的遗传敏感性改变了代谢特征和T2D发病率之间的关系.
主要方法:
- 利用英国生物库数据 (n=93,722) 进行横截面和门德尔随机化分析,以确定与吸烟相关的代谢物.
- 使用弹性净回归开发了与吸烟相关的代谢特征.
- 估计T2D发病率和计算中介比例的危险比率,使用相对过度风险因相互作用 (RERI) 评估相互作用.
主要成果:
- 确定了208种与吸烟有关的代谢物,其中131种通过门德尔随机化确认,包括糖蛋白乙,脂肪酸和脂质.
- 与吸烟相关的代谢特征介导了与目前吸烟相关的T2D风险过剩的38.3% (HR=1.73).
- 代谢特征与T2D风险独立相关 (HR=1.61) 并与T2D遗传风险得分 (RERI=0.81) 和胰岛素抵抗 (RERI=0.47) 有显著的相互作用.
结论:
- 代谢失调是将吸烟与2型糖尿病风险增加联系起来的关键机制.
- 确定的代谢特征有效地调解了吸烟与T2D之间的关联.
- 对T2D或胰岛素抵抗的遗传倾向可以放大吸烟引起的代谢变化对糖尿病风险的不良影响.
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