Human Genetics Center, University of Texas Health Science Center at Houston, P. O. Box 20186, Houston, TX, 77225, USA.
Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI, USA.
Diabetologia. 2020 Feb;63(2):287-295. doi: 10.1007/s00125-019-05031-4. Epub 2019 Dec 4.
AIMS/HYPOTHESIS: To understand the complex metabolic changes that occur long before the diagnosis of type 2 diabetes, we investigated differences in metabolomic profiles in plasma between prediabetic and normoglycaemic individuals for subtypes of prediabetes defined by fasting glucose, 2 h glucose and HbA measures.
Untargeted metabolomics data were obtained from 155 plasma samples from 127 Mexican American individuals from Starr County, TX, USA. None had type 2 diabetes at the time of sample collection and 69 had prediabetes by at least one criterion. We tested statistical associations of amino acids and other metabolites with each subtype of prediabetes.
We identified distinctive differences in amino acid profiles between prediabetic and normoglycaemic individuals, with further differences in amino acid levels among subtypes of prediabetes. When testing all named metabolites, several fatty acids were also significantly associated with 2 h glucose levels. Multivariate discriminative analyses show that untargeted metabolomic data have considerable potential for identifying metabolic differences among subtypes of prediabetes.
CONCLUSIONS/INTERPRETATION: People with each subtype of prediabetes have a distinctive metabolomic signature, beyond the well-known differences in branched-chain amino acids.
Metabolomics data are available through the NCBI database of Genotypes and Phenotypes (dbGaP, accession number phs001166; www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001166.v1.p1).
目的/假设:为了了解 2 型糖尿病诊断前发生的复杂代谢变化,我们研究了空腹血糖、2 小时血糖和 HbA 测量定义的不同 prediabetes 亚型的血浆代谢组学特征之间的代谢组学谱差异。
从美国得克萨斯州 Starr 县的 127 名墨西哥裔美国人的 155 个血浆样本中获得非靶向代谢组学数据。在样本采集时,所有人均没有 2 型糖尿病,其中 69 人至少符合一项标准患有 prediabetes。我们测试了氨基酸和其他代谢物与每种 prediabetes 亚型的统计关联。
我们发现 prediabetic 和血糖正常个体之间的氨基酸谱存在明显差异,并且在 prediabetes 的亚型之间,氨基酸水平也存在进一步的差异。在测试所有命名代谢物时,几种脂肪酸也与 2 小时血糖水平显著相关。多元判别分析表明,非靶向代谢组学数据具有识别 prediabetes 亚型之间代谢差异的巨大潜力。
结论/解释:每种 prediabetes 亚型的个体都有独特的代谢组学特征,除了众所周知的支链氨基酸差异之外。
代谢组学数据可通过 NCBI 的基因型和表型数据库(dbGaP,注册号 phs001166;www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001166.v1.p1)获得。