Population Health Unit, Finnish Institute of Health and Welfare, 00271 Helsinki, Finland.
Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
J Clin Endocrinol Metab. 2022 Sep 28;107(10):2844-2853. doi: 10.1210/clinem/dgac463.
Circulating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D).
We examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention.
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).
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).
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.
循环支链氨基酸（BCAAs）与 2 型糖尿病（T2D）的风险相关。
我们研究了预防 T2D 的生活方式干预在多大程度上与这种关联相互作用，以及在干预过程中 BCAAs 浓度如何变化。
我们通过质谱法每年分析一次的血清空腹 BCAAs 的 k-均值聚类计算轨迹聚类。我们调查了基线 BCAAs、BCAA 轨迹和 BCAAs 变化轨迹是否预测 T2D，以及 BCAAs 在干预组（n=198）和对照组（n=196）中是否以不同的方式预测 T2D。
基线 BCAAs 升高预测了对照组 T2D 的发病率（危险比[HR]每 10 μmol/L 增加 1.05，P=0.01），但在干预组中则不然。整个队列的 BCAAs 浓度在第一年下降（平均-14.9 μmol/L，P<0.001），两组之间没有显著差异。我们确定了 5 个 BCAAs 轨迹聚类和 5 个 BCAAs 变化轨迹聚类。与低 BCAAs 水平轨迹相比，具有高平均 BCAAs 水平的轨迹与 T2D 的 HR 增加相关（最高与最低 BCAAs 轨迹相比，HR 4.0；P=0.01）。仅在干预组中，BCAAs 水平升高的轨迹与降低的轨迹相比，T2D 的 HR 更高（HR 25.4，P<0.001）。
生活方式干预改变了基线 BCAAs 浓度和 BCAAs 轨迹与 T2D 发病率的关联。我们的研究增加了关于生活方式改变对 T2D 风险影响背后机制的累积证据。
