Legacy effects of lifestyle intervention on circulating metabolites in people with impaired glucose tolerance: a cross-sectional analysis of the Da Qing Diabetes Prevention Study

Lifestyle intervention is considered a global consensus for preventing and delaying the development of type 2 diabetes (T2D). This study aims to investigate the differences in metabolites associated with the long-term effect of lifestyle intervention in people with impaired glucose tolerance (IGT). The study enrolled 60 and 57 people with IGT who were originally assigned to the intervention and control (non-intervention) groups in a lifestyle intervention 6-year trial (1986-1992), respectively, as part of the Da Qing Diabetes Prevention Study. In 2006, 14 years after completion of the intervention trial, blood samples were collected for metabolomics analyses and T2D outcomes were assessed. Metabolomics outcomes were not analyzed at baseline. The untargeted metabolomics revealed that 14 plasma metabolites were significantly different between lifestyle intervention and control groups. Targeted metabolomics revealed that plasma concentrations of LysoPC(18:0/0:0) and SM(d18:1/16:1(9Z)) were significantly higher in the lifestyle intervention group compared with the control (16.72 ± 4.75 vs. 1.34 ± 0.40 and 2.60 ± 1.24 vs. 0.40 ± 0.08, P < 0.0001). A 1 μg/mL increase in LysoPC (18:0/0:0) and SM(d18:1/16:1(9Z)) was significantly associated with decreased risk of T2D (odds ratios were 0.82 (95% CI 0.75–0.90) and 0.17 (95% CI 0.07–0.39)) in all participants after adjusting for clinical confounders. In this cross-sectional study, the plasma LysoPC(18:0/0:0) and SM(d18:1/16:1(9Z)) differ between IGT people assigned to intervention and control groups 14 years after the 6-year intervention trial, suggesting they may have been related to the long-term legacy effects of these interventions. Differences in metabolites related to the long-term effects of lifestyle intervention in people with impaired glucose tolerance (IGT) suggest evidence of the long-term legacy effects of these interventions. • 6 years of lifestyle intervention can affect differences in blood metabolites for up to 14 years. • LysoPC(18:0/0:0) and SM(d18:1/16:1(9Z)) show differences after lifestyle intervention or not. • LysoPC(18:0/0:0) and SM(d18:1/16:1(9Z)) might associated with a reduced risk of developing T2D. • LysoPC(18:0/0:0) and SM(d18:1/16:1(9Z)) maybe long-term legacy effects of intervention.