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Associations of plasma glycerophospholipid profile with modifiable lifestyles and incident diabetes in middle-aged and older Chinese

Abstract

Aims/hypothesis

Glycerophospholipid (GPL) perturbance was linked to the pathogenesis of diabetes in animal studies but prospective studies in humans are rare, particularly in Asians. We aimed to investigate the associations between plasma GPLs and incident diabetes and to explore effects of lifestyle on the associations in a Chinese population.

Methods

The study included 1877 community-dwelling Chinese individuals aged 50–70 years (751 men and 1126 women), free of diabetes at baseline and followed for 6 years. A total of 160 GPL species were quantified in plasma at baseline by using high-throughput targeted lipidomics. Log-Poisson regression was used to assess the associations between GPLs and incidence of diabetes.

Results

Over the 6 years of follow-up, 499 participants (26.6%) developed diabetes. After multivariable adjustment, eight GPLs were positively associated with incident diabetes (RRper SD 1.13–1.25; all false-discovery rate [FDR]-corrected p < 0.05), including five novel GLPs, namely phosphatidylcholines (PCs; 16:0/18:1, 18:0/16:1, 18:1/20:3), lysophosphatidylcholine (LPC; 20:3) and phosphatidylethanolamine (PE; 16:0/16:1), and three reported GPLs (PCs 16:0/16:1, 16:0/20:3 and 18:0/20:3). In network analysis, a PC-containing module was positively associated with incident diabetes (RRper SD 1.16 [95% CI 1.06, 1.26]; FDR-corrected p < 0.05). Notably, three of the diabetes-associated PCs (16:0/16:1, 16:0/18:1 and 18:0/16:1) and PE (16:0/16:1) were associated not only with fatty acids in the de novo lipogenesis (DNL) pathway, especially 16:1n-7 (Spearman correlation coefficients = 0.35–0.62, p < 0.001), but also with an unhealthy dietary pattern high in refined grains and low in fish, dairy and soy products (|factor loadings| ≥0.2). When stratified by physical activity levels, the associations of the eight GPLs and the PC module with incident diabetes were stronger in participants with lower physical activity (RRper SD 1.24–1.49, FDR-corrected p < 0.05) than in those with the median and higher physical activity levels (RRper SD 1.03–1.12, FDR-corrected p ≥ 0.05; FDR-corrected pinteraction < 0.05).

Conclusions/interpretation

Eight GPLs, especially PCs associated with the DNL pathway, were positively associated with incident diabetes in a cohort of Chinese men and women. The associations were most prominent in participants with a low level of physical activity.

Graphical abstract

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Fig. 1
Fig. 2

Data availability

The data are available on request from the authors.

Abbreviations

DAG:

Directed acyclic graph

DNL:

De novo lipogenesis

EPIC:

European Prospective Investigation into Cancer and Nutrition

ER:

Endoplasmic reticulum

FDR:

False-discovery rate

GPL:

Glycerophospholipid

HDL-c:

HDL-cholesterol

LC-ESI-MS/MS:

Liquid chromatography electrospray ionisation mass spectrometry

LDL-c:

LDL-cholesterol

LPC:

Lysophosphatidylcholine

MDC-CC:

Malmö Diet and Cancer Cohort

ME:

Module eigenvalue

MET:

Metabolic equivalent

NHAPC:

Nutrition and Health of Aging Population in China

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PE(O):

Alkylphosphatidylethanolamine

PE(P):

Alkenylphosphatidylethanolamine

PLS:

Partial least squares regression

RRR:

Reduced rank regression

TCH:

Total cholesterol

TG:

Triacylglycerol

WC:

Waist circumference

WGCNA:

Weighted gene co-expression network analysis

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Acknowledgements

We sincerely thank F. Wang, Y. Ma, S. Huo, Q. Xiong, H. Yun, Z. Niu, D. Wang, Y. Luo, B. Song, Y. Wu and X. Yang in our research group for their kind assistance during various stages of this study. We further appreciate S. Zhou, X. Pang and all the staff in the local Center for Disease Control and hospitals for their contributions to the fieldwork. We especially acknowledge all the participants involved in this study.

Authors’ relationships and activities

The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Funding

This study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB38000000), the Major Project of the Ministry of Science and Technology of China (2017YFC0909701, 2016YFC1304903), the National Natural Science Foundation of China (81700700, 81970684, 81561128018), the Chinese Academy of Sciences (ZDBS-SSW-DQC-02, KSCX2-EW-R-10, KJZD-EW-L14-2-2) and the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01).

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XL, LS and RZ made substantial contributions to conception and design, acquisition of data, interpretation of data, and revised the manuscript critically for important intellectual content. SSC was central to performing data analyses and drafting the manuscript. GZ, QQW, HY, ZHN and HZ contributed to acquisition of data and revised the manuscript critically for important intellectual content. All authors gave final approval of the version to be published. XL is the guarantor of this work, had full access to all study data, and assumes responsibility for data integrity and analytical accuracy.

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Correspondence to Rong Zeng, Liang Sun or Xu Lin.

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Rong Zeng, Liang Sun and Xu Lin jointly directed this work.

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Chen, S., Zong, G., Wu, Q. et al. Associations of plasma glycerophospholipid profile with modifiable lifestyles and incident diabetes in middle-aged and older Chinese. Diabetologia (2021). https://doi.org/10.1007/s00125-021-05611-3

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Keywords

  • Asian
  • Biomarker
  • Carbohydrate
  • Diabetes
  • Diet
  • Glycerophospholipid
  • Physical activity
  • Prospective study