Abstract
We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73–0.99], P = 0.04) and tended to be directly associated with insulin secretion (β = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 × 10−6) and negatively with hsCRP concentrations at both sampling (r = − 0.22, P = 0.0001) and study follow-up (β = − 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on β-cell function.
Highlights
Well-established lifestyle, and metabolic and genetic factors are currently used for stratifying people at high risk of developing type 2 diabetes (T2D)
Participants who progressed from impaired glucose tolerance (IGT) to diabetes compared with those who did not had reduced levels of indolepropionic acid (IPA) at 1-year follow-up (169 [104–264] vs. 207 [118–304] ng/ml, respectively; P = 0.05)
The association lost its significance when body mass index (BMI) (P = 0.15), fasting (P = 0.07), or 2 h (P = 0.26) plasma glucose at IPA sampling were taken into account
Summary
Well-established lifestyle, and metabolic and genetic factors are currently used for stratifying people at high risk of developing type 2 diabetes (T2D). We recently performed a non-targeted metabolite profiling study in pre-selected participants with impaired glucose tolerance (IGT) from the Finnish Diabetes Prevention Study (DPS) and reported that serum indolepropionic acid (IPA) was associated with a lower likelihood of developing T2D2. We replicated this association in two other independent cohorts[2]. In DPS, IPA was the only metabolite linked with preservation of β-cell function in those who did not develop T2D2. IPA exerts antioxidant and anti-inflammatory effects and possibly ameliorates glucose metabolism[5,6]
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