宫内代谢组学特征与精制谷物摄入量和妊娠糖尿病风险的关系：一项代谢组学全基因组关联研究。

In utero metabolomic signatures of refined grain intake and risk of gestational diabetes: A metabolome-wide association study.

机构信息

Division of Research, Kaiser Permanente Northern California, Oakland, CA.

出版信息

Am J Clin Nutr. 2023 Apr;117(4):731-740. doi: 10.1016/j.ajcnut.2023.02.009. Epub 2023 Feb 11.

DOI:10.1016/j.ajcnut.2023.02.009

PMID:36781127

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10273195/

Abstract

BACKGROUND

Epidemiologic evidence has linked refined grain intake to a higher risk of gestational diabetes (GDM), but the biological underpinnings remain unclear.

OBJECTIVES

We aimed to identify and validate refined grain-related metabolomic biomarkers for GDM risk.

METHODS

In a metabolome-wide association study of 91 cases with GDM and 180 matched controls without GDM (discovery set) nested in the prospective Pregnancy Environment and Lifestyle Study (PETALS), refined grain intake during preconception and early pregnancy and serum untargeted metabolomics were assessed at gestational weeks 10-13. We identified refined grain-related metabolites using multivariable linear regression and examined their prospective associations with GDM risk using conditional logistic regression. We further examined the predictivity of refined grain-related metabolites selected by least absolute shrinkage and selection operator regression in the discovery set and validation set (a random PETALS subsample of 38 individuals with and 336 without GDM).

RESULTS

Among 821 annotated serum (87.4% fasting) metabolites, 42 were associated with refined grain intake, of which 17 (70.6% in glycerolipids, glycerophospholipids, and sphingolipids clusters) were associated with subsequent GDM risk (all false discovery rate-adjusted P values <0.05). Adding 7 of 17 metabolites to a conventional risk factor-based prediction model increased the C-statistic for GDM risk in the discovery set from 0.71 (95% CI: 0.64, 0.77) to 0.77 (95% CI: 0.71, 0.83) and in the validation set from 0.77 (95% CI: 0.69, 0.86) to 0.81 (95% CI: 0.74, 0.89), both with P-for-difference <0.05.

CONCLUSIONS

Clusters of glycerolipids, glycerophospholipids, and sphingolipids may be implicated in the association between refined grain intake and GDM risk, as demonstrated by the significant associations of these metabolites with both refined grains and GDM risk and the incremental predictive value of these metabolites for GDM risk beyond the conventional risk factors. These findings provide evidence on the potential biological underpinnings linking refined grain intake to the risk of GDM and help identify novel disease-related dietary biomarkers to inform diet-related preventive strategies for GDM.

摘要

背景

流行病学证据表明，精制谷物的摄入量与妊娠期糖尿病（GDM）的风险增加有关，但其中的生物学基础仍不清楚。

目的

我们旨在确定并验证与 GDM 风险相关的精制谷物代谢组学生物标志物。

方法

在前瞻性妊娠环境和生活方式研究（PETALS）中嵌套的 91 例 GDM 病例和 180 例无 GDM 的匹配对照（发现集）的全基因组关联研究中，在妊娠 10-13 周时评估了妊娠前和孕早期的精制谷物摄入量和血清非靶向代谢组学。我们使用多变量线性回归确定了与精制谷物相关的代谢产物，并使用条件逻辑回归检查了它们与 GDM 风险的前瞻性关联。我们进一步在发现集和验证集（随机 PETALS 子样本，包括 38 例 GDM 患者和 336 例无 GDM 患者）中检验了由最小绝对收缩和选择算子回归选择的与精制谷物相关的代谢产物的预测能力。

结果

在 821 种注释的血清（87.4%为空腹）代谢产物中，有 42 种与精制谷物的摄入量有关，其中 17 种（甘油磷脂、甘油磷酸脂和神经鞘脂簇中占 70.6%）与随后的 GDM 风险有关（所有经错误发现率校正的 P 值均<0.05）。在发现集中，将 17 种代谢产物中的 7 种添加到基于传统危险因素的预测模型中，可将 GDM 风险的 C 统计量从 0.71（95%CI：0.64，0.77）提高到 0.77（95%CI：0.71，0.83），在验证集中从 0.77（95%CI：0.69，0.86）提高到 0.81（95%CI：0.74，0.89），差异均有统计学意义（均 P<0.05）。

结论

甘油磷脂、甘油磷酸脂和神经鞘脂簇可能与精制谷物的摄入量与 GDM 风险之间的关联有关，这表明这些代谢产物与精制谷物和 GDM 风险均有显著关联，并且这些代谢产物对 GDM 风险的预测价值高于传统危险因素。这些发现为精制谷物的摄入量与 GDM 风险之间的潜在生物学基础提供了证据，并有助于确定与疾病相关的新型饮食生物标志物，为 GDM 的饮食相关预防策略提供信息。