Healthy lifestyle and related metabolomic signatures associated with decreased risk and delayed progression of type 2 diabetes mellitus transitions: a large prospective cohort study

Abstract

Background

To evaluate dynamic associations of a comprehensive healthy lifestyle and related metabolic signatures with the progression trajectory of type 2 diabetes mellitus (T2DM).

Methods

From the UK Biobank cohort, we identified 305,349 participants without diabetes or diabetes-related complications, 152,901 of whom had available metabolite data. A healthy lifestyle score (HLS) was constructed using eight factors. Elastic net regression models were used to identify lifestyle-related metabolomic signatures. Multistate models were used to evaluate the dynamic associations of HLS and related metabolomic signatures with the incidence and progression of T2DM. Accelerated failure time models assessed whether HLS and related metabolomic signatures were associated with relative time delays in T2DM progression.

Results

During a median follow-up of 13.84 years, 7998 participants developed incident T2DM. We identified 139 metabolites representing healthy lifestyles. HLS and related metabolomic signatures were inversely associated with the risk of T2DM transitions. The HRs per SD increase of lifestyle-related metabolites were 0.96, 0.89, 0.95, and 0.87 for transitions from non-T2DM to incident T2DM, to death, from incident T2DM to complications, and to death. HLS and related metabolomic signatures were both significantly associated with delays in transitions from non-T2DM to incident T2DM, to death, and from T2DM to complications, to death, with prolonged onset time ranging from 0.22 to 1.75 years for HLS and 0.24 to 0.74 years for metabolomic signatures, respectively.

Conclusions

The findings highlight the significance of adherence to a healthy lifestyle in preventing the onset and progression of T2DM from behaviors and metabolomics perspectives.