Longitudinal Branched-Chain Amino Acids, Lifestyle Intervention, and Type 2 Diabetes in the Finnish Diabetes Prevention Study

Jemina Kivelä, Jelena Meinilä, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström, Jemina Kivelä, Jelena Meinilä, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström

Abstract

Context: Circulating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D).

Objective: We examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention.

Methods: We computed trajectory clusters by k-means clustering of serum fasting BCAAs analyzed annually by mass spectrometry during a 4-year intervention. We investigated whether baseline BCAAs, BCAA trajectories, and BCAA change trajectories predicted T2D and whether BCAAs predicted T2D differently in the intervention (n = 198) and control group (n = 196).

Results: Elevated baseline BCAAs predicted the incidence of T2D in the control group (hazard ratio [HR] 1.05 per 10 μmol/L, P = 0.01), but not in the intervention group. BCAA concentration decreased during the first year in the whole cohort (mean -14.9 μmol/L, P < 0.001), with no significant difference between the groups. We identified 5 BCAA trajectory clusters and 5 trajectory clusters for the change in BCAAs. Trajectories with high mean BCAA levels were associated with an increased HR for T2D compared with the trajectory with low BCAA levels (trajectory with highest vs lowest BCAA, HR 4.0; P = 0.01). A trajectory with increasing BCAA levels had a higher HR for T2D compared with decreasing trajectory in the intervention group only (HR 25.4, P < 0.001).

Conclusion: Lifestyle intervention modified the association of the baseline BCAA concentration and BCAA trajectories with the incidence of T2D. Our study adds to the accumulating evidence on the mechanisms behind the effect of lifestyle changes on the risk of T2D.

Trial registration: ClinicalTrials.gov NCT00518167.

Keywords: amino acids; branched-chain; cluster analysis; diabetes mellitus; lifestyle intervention; metabolome; type 2.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Flowchart of participants. Abbreviations: DPS, Diabetes Prevention Study; BMI, body mass index; BCAA, branched-chain amino acids; T2D, type 2 diabetes.
Figure 2.
Figure 2.
Joint effect of intervention and baseline branched-chain amino acids (BCAA) concentration on type 2 diabetes incidence. Participants in the control group with a low baseline BCAA comprise the reference group in Cox regression model adjusted for age, sex, education, smoking, body mass index (BMI), leisure-time physical activity, saturated fat intake, fiber intake, and blood triglycerides. The y-axis is on logarithmic scale.
Figure 3.
Figure 3.
Branched-chain amino acid (BCAA) change from baseline to year 4 in the intervention and control groups. Error bars indicate 95% CI.
Figure 4.
Figure 4.
Trajectory clusters of BCAA levels from baseline to 4 years. Cluster size: A = 118, B = 106, C = 69, D = 48, E = 23.
Figure 5.
Figure 5.
Trajectory clusters of branched-chain amino acid (BCAA) change. Cluster size: cA n = 130, cB n = 97, cC n = 93, cD n = 23, cE n = 21.

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