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胰岛素抵抗和糖尿病的血浆代谢标志物与帕金森病发病风险。

Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson's Disease.

机构信息

Population Health Sciences Program, Harvard University, Cambridge, MA, USA.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

出版信息

J Parkinsons Dis. 2020;10(3):1011-1021. doi: 10.3233/JPD-191896.

Abstract

BACKGROUND

Although there is evidence of shared dysregulated pathways between diabetes and Parkinson's disease, epidemiologic research on an association between the two diseases has produced inconsistent results.

OBJECTIVE

We aimed to assess whether known metabolomic markers of insulin resistance and diabetes are also associated with Parkinson's disease development.

METHODS

We conducted a nested case-control study among Nurses' Health Study and Health Professionals Follow-up Study participants who had provided blood samples up to twenty years prior to Parkinson's diagnosis. Cases were matched to risk-set sampled controls by age, sex, fasting status, and time of blood collection. Participants provided covariate information via regularly collected cohort questionnaires. We used conditional logistic regression models to assess whether plasma levels of branched chain amino acids, acylcarnitines, glutamate, or glutamine were associated with incident development of Parkinson's disease.

RESULTS

A total of 349 case-control pairs were included in this analysis. In the primary analyses, none of the metabolites of interest were associated with Parkinson's disease development. In investigations of the association between each metabolite and Parkinson's disease at different time intervals prior to diagnosis, some metabolites showed marginally significant association but, after correction for multiple testing, only C18 : 2 acylcarnitine was significantly associated with Parkinson's disease among subjects for whom blood was collected less than 60 months prior to case diagnosis.

CONCLUSIONS

Plasma levels of diabetes-related metabolites did not contribute to predict risk of Parkinson's disease. Further investigation of the relationship between pre-diagnostic levels of diabetes-related metabolites and Parkinson's disease in other populations is needed to confirm these findings.

摘要

背景

尽管有证据表明糖尿病和帕金森病之间存在共同失调的途径,但流行病学研究表明这两种疾病之间存在关联,但结果并不一致。

目的

我们旨在评估胰岛素抵抗和糖尿病的已知代谢标志物是否也与帕金森病的发展有关。

方法

我们在护士健康研究和健康专业人员随访研究参与者中进行了一项嵌套病例对照研究,这些参与者在帕金森病诊断前最多提供了二十年的血液样本。病例通过年龄、性别、禁食状态和采血时间与风险集抽样对照相匹配。参与者通过定期收集的队列问卷提供协变量信息。我们使用条件逻辑回归模型来评估支链氨基酸、酰基辅酶 A、谷氨酸或谷氨酰胺的血浆水平是否与帕金森病的发生发展有关。

结果

共有 349 对病例对照纳入本分析。在主要分析中,没有一种感兴趣的代谢物与帕金森病的发展有关。在对每种代谢物与诊断前不同时间间隔的帕金森病之间的关联进行调查时,一些代谢物显示出边缘显著关联,但在进行多次检验校正后,只有 C18:2 酰基辅酶 A 在血液采集时间少于 60 个月的病例诊断前的受试者中与帕金森病显著相关。

结论

与糖尿病相关的代谢物的血浆水平不能预测帕金森病的风险。需要在其他人群中进一步研究诊断前与糖尿病相关的代谢物水平与帕金森病之间的关系,以证实这些发现。

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