Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study

Abstract

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.

High‐Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue Inflammation and Metabolism in C57BL/6J Mice

“…Changes in the levels of amino acid metabolism‐related compounds have been reported under obese and diabetic conditions, such as lower levels of citrulline in blood and higher choline, lysine, and leucine content . The levels of branched chain amino acids become elevated in blood years before the onset of T2D . In the fat depots of DIO mice, we observed a reduced effect of the HF diet on citrulline but decreased levels of other amino acids.…”

Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes

“…In this case, the increase in hippuric acid most likely reflects the modulation of the microbiota quality, and not directly the food source. Moreover, preliminary analyses indicate that there is correlation between hippuric acid and another microbiota‐produced compound, indolepropionic acid, which we have recently reported as a metabolite related to lower likelihood to develop T2D in the DPS study . This most likely suggests that the dietary changes have induced change in the composition of colonic microbiota, followed by higher levels of potentially health‐protective diet‐derived microbial metabolites in the circulation.…”

Metabolic Profiling of High Egg Consumption and the Associated Lower Risk of Type 2 Diabetes in Middle‐Aged Finnish Men

“…The distinct profiles between the T2D cases and controls, despite the long mean follow‐up of 19.3 years was interesting. We confirmed the previous findings from the Finnish Diabetes Prevention Study, which showed that tyrosine reflected higher risk of T2D whereas PUFA‐ and OCFA‐containing (lyso)PCs indicated the opposite. Other aromatic amino acids or BCAA, however, did not differ between T2D cases and controls, though we observed higher levels of γ‐glutamylated‐BCAAs in the lower‐egg‐intake groups which positively correlated with the metabolic profiles of the T2D cases.…”