Microbiota-related metabolites and the risk of type 2 diabetes

OBJECTIVE: Recent studies have highlighted the significance of 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: 5,181 participants from the cross-sectional METabolic Syndrome In Men (METSIM) study that included Finnish men (age 57 ± 7 years, body mass index 26.5 ± 3.5 kg/m²) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. Based on an oral glucose tolerance test, Matsuda ISI and Disposition index 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-linoleoyl-glycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.

CONCLUSIONS: Several novel and previously reported microbial metabolites related to 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.