Inter-individual differences in the response to an exercise training intervention in patients with metabolic syndrome
Authors: Von Korn P , Kia S , Lechner K , Dinges S , Duvinage A , Scherr J , Landmesser U , Halle M , Kraenkel N 
Published: November 2020

Abstract

Background
Regular physical exercise and standardized exercise training (ET) programmes positively affect a number of metabolic and cardiovascular risk factors. Yet, response to ET varies between patients and between individual risk parameters. We investigated inter-individual responses regarding blood pressure, heart rate, lipids and glucose metabolism, as well as physical fitness to a 16-weeks supervised exercise training protocol in patients with metabolic syndrome (MetS).

Methods
29 MetS patients (20M/9F, age 52–70 y, BMI 24.9–38.2 kg/m2) exercised for 16 weeks in a supervised setting with varying volume and intensity. At baseline and at completion of the programme, blood pressure, heart rate, plasma lipids, glucose and insulin levels, as well as physical fitness were assessed, as were quantitative and morphological leukocyte parameters, cytokines and 86 metabolically relevant plasma proteins. Associations between individual risk parameters, leukocyte profile and plasma proteins were explored by recursive partitioning and network analysis. T-distributed stochastic neighbor embedding and hierarchical clustering were used for clustering based on cardiometabolic target parameters at 16 weeks.

Results
In the whole cohort, VO2peak increased and plasma counts of total leukocytes, neutrophils, monocytes (classical and intermediate), NK cells and effector and regulatory CD4+ lymphocytes, as well as circulating endothelial microvesicles were reduced at the end of the ET programme versus baseline. Plasma levels of carboxylesterase 1 decreased and soluble interleukin-7 receptor increased. Based on patient's cardio-metabolic parameters, three clusters were identified: cluster 1 had lower values of triglycerides, total and LDL cholesterol, cluster 2 had higher levels of triglycerides and cluster 3 had a greater heart rate recovery and lower insulin levels, but higher total and LDL cholesterol levels at follow-up. In cluster 1, absolute and relative NK cell counts were decreased and no morphological activation was observed. In cluster 2, reduced relative counts of NK-T cells were decreased, but their size was increased. In cluster 3, size of most effector leukocyte subtypes (CD8+, CD4+ Teff, NK-T, neutrophils) was increased at follow-up versus baseline. Network analysis suggested four distinct networks of (1) triglycerides, (2) VO2peak, (3) diastolic BP and (4) a cluster containing total and LDL cholesterol, insulin and HR recovery, each associated with partly distinct sets of plasma proteins and leukocyte parameters.

Conclusion
Despite improved physical fitness in all patients participating in the 16 weeks ET programme, inter-individual differences regarding cardio-metabolic target parameters and leukocyte activation was evident. Identification of specific leukocyte responses and of plasma protein “fingerprints” might help to optimize patient-specific prevention programmes, integrating medication and lifestyle optimization.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): DZHK, DSHF