A Lipid Signature with Perturbed Triacylglycerol Co-Regulation, Identified from Targeted Lipidomics, Predicts Risk for Type 2 Diabetes and Mediates the Risk from Adiposity in Two Prospective Cohorts of Chinese Adults.

Abstract

BACKGROUND:

The roles of individual and co-regulated lipid molecular species in the development of type 2 diabetes (T2D) and mediation from metabolic risk factors remain unknown.

METHODS:

We conducted profiling of 166 plasma lipid species in 2 nested case-control studies within 2 independent cohorts of Chinese adults, the Dongfeng-Tongji and the Jiangsu non-communicable disease cohorts. After 4.61 (0.15) and 7.57 (1.13) years' follow-up, 1039 and 520 eligible participants developed T2D in these 2 cohorts, respectively, and controls were 1:1 matched to cases by age and sex.

RESULTS:

We found 27 lipid species, including 10 novel ones, consistently associated with T2D risk in the 2 cohorts. Differential correlation network analysis revealed significant correlations of triacylglycerol (TAG) 50:3, containing at least one oleyl chain, with 6 TAGs, at least 3 of which contain the palmitoyl chain, all downregulated within cases relative to controls among the 27 lipids in both cohorts, while the networks also both identified the oleyl chain-containing TAG 50:3 as the central hub. We further found that 13 of the 27 lipids consistently mediated the association between adiposity indicators (body mass index, waist circumference, and waist-to-height ratio) and diabetes risk in both cohorts (all P < 0.05; proportion mediated: 20.00%, 17.70%, and 17.71%, and 32.50%, 28.73%, and 33.86%, respectively).

CONCLUSIONS:

Our findings suggested notable perturbed co-regulation, inferred from differential correlation networks, between oleyl chain- and palmitoyl chain-containing TAGs before diabetes onset, with the oleyl chain-containing TAG 50:3 at the center, and provided novel etiological insight regarding lipid dysregulation in the progression from adiposity to overt T2D.

• Authors: Gaokun Qiu, Hao Wang, Qi Yan, Hongxia Ma, Rundong Niu, Yanshou Lei, Yang Xiao, Lue Zhou, Handong Yang, Chengwei Xu, Xiaomin Zhang, Meian He, Huiru Tang, Zhibin Hu, An Pan, Hongbing Shen, Tangchun Wu
• Journal: Clinical chemistry (Clin Chem) Vol. 68 Issue 8 Pg. 1094-1107 (07 27 2022) ISSN: 1530-8561 [Electronic] England
• PMID: 35708664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Triglycerides

Topics

• Adiposity
• Adult
• China
• Diabetes Mellitus, Type 2
• Humans
• Lipidomics
• Obesity
• Prospective Studies
• Risk Factors
• Triglycerides