十年间代谢组学谱的变化与随后 2 型糖尿病发病风险：来自护士健康研究的结果。
Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes: Results from the Nurses' Health Study.
机构信息
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA.
出版信息
EBioMedicine. 2022 Jan;75:103799. doi: 10.1016/j.ebiom.2021.103799. Epub 2021 Dec 31.
BACKGROUND
Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk.
METHODS
We conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status.
FINDINGS
The 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78).
INTERPRETATION
Repeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.
背景
代谢组学图谱与 2 型糖尿病（T2D）风险始终相关，但缺乏关于长期代谢物变化与 T2D 发病之间关系的证据。我们研究了 10 年血浆代谢物变化与随后 T2D 风险之间的关联。
方法
我们在护士健康研究（Nurses' Health Study）中开展了一项 T2D 病例对照研究的嵌套研究（244 例病例，244 例匹配对照）。在 1989/1990 年和 2000/2001 年采集参与者的血液样本进行了多次代谢组学分析（170 种靶向代谢物），T2D 发生在 2002 年至 2008 年期间。我们使用条件逻辑回归模型将 10 年的代谢物变化（Δ 值）与随后的 T2D 风险相关联，该模型调整了基线代谢物水平、BMI、饮食质量、身体活动和吸烟状态的基线水平和同期变化。
结果
31 种代谢物的 10 年变化与随后的 T2D 风险相关（错误发现率校正的 p 值[FDR] <0.05）。与高 T2D 风险相关的前三个 10 年变化是（每个标准差的优势比[OR]，95%CI）：异亮氨酸（2.72，1.97-3.79）、亮氨酸（2.53，1.86-3.47）和缬氨酸（1.93，1.52-2.44）；其他高风险相关的代谢物变化包括丙氨酸、三酰基/二酰基甘油片段、短链酰基辅酶 A、磷脂酰乙醇胺、一些维生素和胆汁酸（SD 之间的 OR 为 1.31-1.82）。与低 T2D 风险相关的前三个 10 年代谢物变化是（SD 的 OR，95%CI）：N-乙酰天冬氨酸（0.54，0.42-0.70）、C20:0 溶血磷脂酰乙醇胺（0.68，0.56-0.82）和 C16:1 神经鞘磷脂（0.68，0.56-0.83）；其他神经鞘磷脂、血浆类脂、谷氨酰胺和甘氨酸的 10 年变化也与随后较低的 T2D 风险相关（SD 之间的 OR 为 0.66-0.78）。
解释
反映氨基酸和脂质代谢长期恶化的重复代谢组学图谱与随后的 T2D 发病风险相关。
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