Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study.
Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study.
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DOI：
10.1038/srep46337
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发表时间：
2017-04-11
影响因子：
4.6
通讯作者：
Uusitupa M
中科院分区：
文献类型：
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作者：
de Mello VD;Paananen J;Lindström J;Lankinen MA;Shi L;Kuusisto J;Pihlajamäki J;Auriola S;Lehtonen M;Rolandsson O;Bergdahl IA;Nordin E;Ilanne-Parikka P;Keinänen-Kiukaanniemi S;Landberg R;Eriksson JG;Tuomilehto J;Hanhineva K;Uusitupa M
包括代谢组学在内的大规模分析技术拓宽了与2型糖尿病（T2D）发病机制相关的新发现的可能性。通过应用非靶向代谢组学方法，我们通过检查参加芬兰糖尿病预防研究（DPS）的两组个体，研究了血清代谢物谱是否可以预测糖耐量受损的典型研究人群中的T2D；早期发展为T2D （n = 96）或在15年随访期间未转变为T2D （n = 104）的患者。一些新的代谢物与较低的发生T2D的可能性相关，包括吲哚和脂质相关代谢物。较高的吲哚丙酸与DPS患者发生T2D的可能性降低有关。有趣的是，在没有T2D的患者中，吲哚丙酸和各种脂质分别与更好的胰岛素分泌和敏感性相关。此外，这些代谢物与低度炎症呈负相关。我们在一个芬兰和一个瑞典人群中重复了吲哚丙酸与T2D风险之间的关联。我们认为，肠道微生物产生的代谢物吲哚丙酸是T2D发展的潜在生物标志物，可能通过保存β细胞功能来调节其保护作用。与T2D相关的新型脂质代谢物可能部分通过增强胰岛素敏感性来发挥作用。
Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.