INTRODUCTION Several plasma metabolites have been associated with insulin resistance and type 2 diabetes mellitus. OBJECTIVES We aimed to identify plasma metabolites associated with different indices of early disturbances in glucose metabolism and insulin sensitivity. METHODS This cross-sectional study was conducted in a subsample of the Leiden Longevity Study comprising individuals without a history of diabetes mellitus (n = 233) with a mean age of 63.3 ± 6.7 years of which 48.1% were men. We tested for associations of fasting glucose, fasting insulin, HOMA-IR, Matsuda Index, Insulinogenic Index and glycated hemoglobin with metabolites (Swedish Metabolomics Platform) using linear regression analysis adjusted for age, sex and BMI. Results were validated internally using an independent metabolomics platform (Biocrates platform) and replicated externally in the independent Netherlands Epidemiology of Obesity (NEO) study (Metabolon platform) (n = 545, mean age of 55.8 ± 6.0 years of which 48.6% were men). Moreover, in the NEO study, we replicated our analyses in individuals with diabetes mellitus (cases: n = 36; controls = 561). RESULTS Out of the 34 metabolites, a total of 12 plasma metabolites were associated with different indices of disturbances in glucose metabolism and insulin sensitivity in individuals without diabetes mellitus. These findings were validated using a different metabolomics platform as well as in an independent cohort of non-diabetics. Moreover, tyrosine, alanine, valine, tryptophan and alpha-ketoglutaric acid levels were higher in individuals with diabetes mellitus. CONCLUSION We found several plasma metabolites that are associated with early disturbances in glucose metabolism and insulin sensitivity of which five were also higher in individuals with diabetes mellitus.

中文翻译：

---

非糖尿病中年人的代谢组学分析显示，代谢物会影响早期的葡萄糖紊乱和胰岛素敏感性。

引言几种血浆代谢物与胰岛素抵抗和2型糖尿病有关。目的我们旨在鉴定与葡萄糖代谢和胰岛素敏感性的早期紊乱的不同指标相关的血浆代谢物。方法该横断面研究是在莱顿长寿研究的子样本中进行的，该样本包括没有糖尿病史（n = 233），平均年龄为63.3±6.7岁的个体，其中男性为48.1％。我们使用针对年龄，性别和BMI调整的线性回归分析，测试了空腹血糖，空腹胰岛素，HOMA-IR，松田指数，致胰岛素指数和糖化血红蛋白与代谢物（瑞典代谢组学平台）的关联。结果使用独立的代谢组学平台（Biocrates平台）在内部进行验证，并在独立的荷兰肥胖症流行病学（NEO）研究（Metabolon平台）中进行外部复制（n = 545，平均年龄为55.8±6.0岁，其中男性为48.6％）。 。此外，在NEO研究中，我们在糖尿病患者中重复了我们的分析（案例：n = 36；对照组= 561）。结果在34种代谢产物中，共有12种血浆代谢产物与无糖尿病患者的糖代谢紊乱和胰岛素敏感性的不同指标相关。使用不同的代谢组学平台以及独立的非糖尿病人群验证了这些发现。此外，酪氨酸，丙氨酸，缬氨酸，糖尿病患者的色氨酸和α-酮戊二酸水平较高。结论我们发现了几种血浆代谢产物，这些代谢产物与葡萄糖代谢和胰岛素敏感性的早期紊乱有关，其中5种在糖尿病患者中也较高。