Microbiota-Related Metabolites and the Risk of Type 2 Diabetes
Microbiota-Related Metabolites and the Risk of Type 2 Diabetes
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DOI：
10.2337/dc19-2533
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发表时间：
2020-06-01
期刊：
影响因子：
16.2
通讯作者：
Laakso, Markku
中科院分区：
文献类型：
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作者：
Vangipurapu, Jagadish;Fernandes Silva, Lilian;Laakso, Markku
目的近年来的研究强调了微生物组在人类健康和疾病中的重要意义。微生物区系产生的代谢物的变化与几种疾病有关。我们的目标是确定与2型糖尿病相关的微生物组代谢物。研究设计和方法我们的研究包括5181名来自男性代谢综合征(METSIM)横断面研究的参与者，其中包括拥有代谢组学数据的芬兰男性(年龄57+/-7岁，BMI 26.5+/-3.5 kg/m(2))。代谢组学分析是基于空腹血浆样本进行的。在口服葡萄糖耐量试验的基础上，计算松田ISI和倾向指数作为胰岛素敏感性和胰岛素分泌的标志物。共有4851名参与者进行了7.4年的随访，其中522名参与者患上了2型糖尿病。结果肌酸、1-棕榈油酰甘油(16：1)、尿酸、2-羟基丁酸酯/2-羟基异丁酸酯、黄嘌呤、黄尿酸、犬尿酸、3-(4-羟基苯基)乳酸、1-油酰甘油(18：1)、1-肉豆蔻酰甘油(14：0)、二甲基甘氨酸和2-羟基马尿酸(水杨酸)与2型糖尿病的危险性显著相关。这些代谢物与胰岛素分泌减少或胰岛素敏感性降低或两者兼而有之。在与2型糖尿病风险降低相关的代谢物中，1-亚油酰甘油磷胆碱(18：2)显著降低了2型糖尿病的风险。结论与肠道微生物区系相关的几种新的微生物代谢物与2型糖尿病发病风险增加有关，它们还与胰岛素分泌减少和胰岛素敏感性有关。微生物代谢产物是2型糖尿病风险的重要生物标志物。
OBJECTIVE Recent studies have highlighted the significance of the microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes. RESEARCH DESIGN AND METHODS Our study included 5,181 participants from the cross-sectional Metabolic Syndrome in Men (METSIM) study that included Finnish men (age 57 +/- 7 years, BMI 26.5 +/- 3.5 kg/m(2)) having metabolomics data available. Metabolomics analysis was performed based on fasting plasma samples. On the basis of an oral glucose tolerance test, Matsuda ISI and disposition index values were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit, and 522 participants developed type 2 diabetes. RESULTS Creatine, 1-palmitoleoylglycerol (16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol (18:1), 1-myristoylglycerol (14:0), dimethylglycine, and 2-hydroxyhippurate (salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoylglycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes. CONCLUSIONS Several novel and previously reported microbial metabolites related to the gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes.