Jia Xiaojing, Lin Hong, Ding Yilan, Gu Xuejiang, Wang Shuangyuan, Xu Yu, Xu Min, Zhao Xinjie, Chen Lulu, Zeng Tianshu, Shi Lixin, Su Qing, Chen Yuhong, Yu Xuefeng, Yan Li, Qin Guijun, Wan Qin, Chen Gang, Tang Xulei, Gao Zhengnan, Shen Feixia, Hu Ruying, Luo Zuojie, Qin Yingfen, Chen Li, Hou Xinguo, Huo Yanan, Li Qiang, Wang Guixia, Zhang Yinfei, Liu Chao, Wang Youmin, Wu Shengli, Yang Tao, Deng Huacong, Zhao Jiajun, Mu Yiming, Ning Guang, Wang Weiqing, Bi Yufang, Lu Jieli
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
J Clin Endocrinol Metab. 2025 Jan 21;110(2):441-451. doi: 10.1210/clinem/dgae483.
Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies.
This work aimed to investigate associations and genetic susceptibility between serum MCFAs and diabetes risk.
We investigated baseline serum MCFAs (n = 5) in a nested case-control study comprising incident diabetes cases (n = 1707) and matched normoglycemic control individuals (n = 1707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants.
In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% CI) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = .042, .034, and .037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Statistically significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = .003).
These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.
新兴研究揭示了膳食中链脂肪酸（MCFAs）与葡萄糖稳态之间的关联。然而，在前瞻性队列研究中，血清MCFAs与糖尿病发病率之间的关系以及与遗传易感性的潜在相互作用仍不明确。
本研究旨在探讨血清MCFAs与糖尿病风险之间的关联及遗传易感性。
在中国心血管代谢疾病与癌症队列研究中，我们开展了一项巢式病例对照研究，纳入了新发糖尿病病例（n = 1707）和匹配的血糖正常对照个体（n = 1707），检测了其基线血清MCFAs（n = 5）。研究了MCFAs与2型糖尿病（T2DM）之间的总体关联以及按糖尿病遗传易感性分层后的关联。基于86个与T2DM相关的基因变异计算遗传风险评分（GRS）。
在完全调整的条件逻辑回归模型中，血清辛酸和壬酸与糖尿病风险呈负剂量反应关系，优势比（95% CI）分别为0.90（0.82 - 0.98）和0.84（0.74 - 0.95）。亚组分析表明，在缺乏身体活动的个体中，MCFAs与新发糖尿病之间的负相关更为明显（辛酸、壬酸和癸酸的P交互作用分别为0.042、0.034和0.037）。此外，与低遗传风险个体相比，高遗传风险个体中辛酸与糖尿病风险的负相关显著增强。在辛酸与GRS对T2DM风险的影响上观察到具有统计学意义的交互作用（P交互作用 = 0.003）。
这些发现提供了证据支持血清MCFAs与T2DM风险之间的负相关，并揭示了遗传易感性与循环辛酸在调节糖尿病风险中的潜在相互作用。
