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A Proactive Intervention Study in Metabolic Syndrome High-Risk Populations Using Phenome-Based Actionable P4 Medicine Strategy

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Abstract

The integration of predictive, preventive, personalized, and participatory (P4) healthcare advocates proactive intervention, including dietary supplements and lifestyle interventions for chronic disease. Personal profiles include deep phenotypic data and genetic information, which are associated with chronic diseases, can guide proactive intervention. However, little is known about how to design an appropriate intervention mode to precisely intervene with personalized phenome-based data. Here, we report the results of a 3-month study on 350 individuals with metabolic syndrome high-risk that we named the Pioneer 350 Wellness project (P350). We examined: (1) longitudinal (two times) phenotypes covering blood lipids, blood glucose, homocysteine (HCY), and vitamin D3 (VD3), and (2) polymorphism of genes related to folic acid metabolism. Based on personalized data and questionnaires including demographics, diet and exercise habits information, coaches identified 'actionable possibilities', which combined exercise, diet, and dietary supplements. After a 3-month proactive intervention, two-thirds of the phenotypic markers were significantly improved in the P350 cohort. Specifically, we found that dietary supplements and lifestyle interventions have different effects on phenotypic improvement. For example, dietary supplements can result in a rapid recovery of abnormal HCY and VD3 levels, while lifestyle interventions are more suitable for those with high body mass index (BMI), but almost do not help the recovery of HCY. Furthermore, although people who implemented only one of the exercise or diet interventions also benefited, the effect was not as good as the combined exercise and diet interventions. In a subgroup of 226 people, we examined the association between the polymorphism of genes related to folic acid metabolism and the benefits of folate supplementation to restore a normal HCY level. We found people with folic acid metabolism deficiency genes are more likely to benefit from folate supplementation to restore a normal HCY level. Overall, these results suggest: (1) phenome-based data can guide the formulation of more precise and comprehensive interventions, and (2) genetic polymorphism impacts clinical responses to interventions. Notably, we provide a proactive intervention example that is operable in daily life, allowing people with different phenome-based data to design the appropriate intervention protocol including dietary supplements and lifestyle interventions.

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Data Availability

The datasets of the current study are available from the corresponding author upon reasonable request.

Abbreviations

PLA:

People's liberation army

P4:

Predictive, preventive, personalized, and participatory

P350:

Pioneer 350 wellness project

HCY:

Homocysteine

VD3 :

Vitamin D3

BMI:

Body mass index

P100:

Pioneer 100 wellness project

PD3:

Personal, dense, dynamic data

FPG:

Fasting plasma glucose

HbA1C:

Glycosylated hemoglobin, type A1C

TC:

Total cholesterol

TG:

Triglyceride

LDL-C:

Low-density lipoprotein cholesterol

HDL-C:

High-density leptin cholesterol

COVID-19:

Coronavirus disease 2019

DBP:

Diastolic blood pressure

SBP:

Systolic blood pressure

MTHFR:

5,10-Methylenetetrahydrofolate reductase

MTRR:

Methionine synthase reductase

SL:

Supplements and lifestyle intervention group

S:

Supplements intervention group

L:

Lifestyle intervention group

GWASs:

Genome-wide association studies

D&E:

Participants in the SL group who performed both diet and exercise interventions

D|E:

Participants in the SL group who received either diet or exercise intervention

STRONGER:

Participants with “normal” and “slightly weak” folate utilization capacity

WEAKER:

Participants with “relatively weak” and “weak” folate utilization capacity

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

References

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Acknowledgements

Special thanks to “China Health Promotion Foundation”, “TSI Group Co., Ltd.” for their strong support of this study. Additionally, we acknowledge the funding support provided by Bei**g Municipal Science and Technology Commission (No. Z18110700160000, No. Z181100001618014), which significantly contributed to the success of this study.

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Authors and Affiliations

Authors

Contributions

ZHu, XMao, QHuang, QZheng, WLv, LHood, FWang and FWu conceived and supervised the project. ZHu, XMao, DFu and CLu enrolled the participants. QHuang designed the analytical approach and performed data analysis. QHuang, ZHu, QZeng, QFang and CZeng edited the manuscript critically. All authors contributed to have approved the final manuscript.

Corresponding authors

Correspondence to Zhiyuan Hu, Qiang Zeng, Qiaojun Fang or Leroy Hood.

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Conflict of interest

There is no conflict of interest regarding the publication of this paper. Leroy Hood and Zhiyuan Hu are the Editorial Board Members of Phenomics, and they were not involved in reviewing this paper.

Ethical Approval

This study was approved by the ethics of Chinese PLA General Hospital (S2019-190-02).

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

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Supplementary file2 (XLSX 12 KB)

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Huang, Q., Hu, Z., Zheng, Q. et al. A Proactive Intervention Study in Metabolic Syndrome High-Risk Populations Using Phenome-Based Actionable P4 Medicine Strategy. Phenomics 4, 91–108 (2024). https://doi.org/10.1007/s43657-023-00115-z

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  • DOI: https://doi.org/10.1007/s43657-023-00115-z

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