Diabetes Care
Abstract
OBJECTIVEComprehensive assessment of serum lipidomic aberrations before type 2 diabetes (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR).
RESEARCH DESIGN AND METHODSIn the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score–matched control subjects (n= 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n= 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated.
RESULTSAt the level of false-discovery rate <0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)–plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non–PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices.
CONCLUSIONSThese findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals.
| 论文编号: | DOI:10.2337/dc19-0100 |
| 论文题目: | High-Coverage Targeted Lipidomics Reveals Novel Serum Lipid Predictors and Lipid Pathway Dysregulation Antecedent to Type 2 Diabetes Onset in Normoglycemic Chinese Adults |
| 英文论文题目: | High-Coverage Targeted Lipidomics Reveals Novel Serum Lipid Predictors and Lipid Pathway Dysregulation Antecedent to Type 2 Diabetes Onset in Normoglycemic Chinese Adults |
| 第一作者: | Jieli Lu, Sin Man Lam, Qin Wan, Lixin Shi, Yanan Huo, Lulu Chen, Xulei Tang, Bowen Li, Xueyan Wu, Kui Peng, Mian Li, Shuangyuan Wang, Yu Xu, Min Xu, Yufang Bi, Guang Ning, Guanghou Shui, Weiqing Wang |
| 英文第一作者: | Jieli Lu, Sin Man Lam, Qin Wan, Lixin Shi, Yanan Huo, Lulu Chen, Xulei Tang, Bowen Li, Xueyan Wu, Kui Peng, Mian Li, Shuangyuan Wang, Yu Xu, Min Xu, Yufang Bi, Guang Ning, Guanghou Shui, Weiqing Wang |
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| 发表年度: | 2019-08-28 |
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| 摘要: | OBJECTIVEComprehensive assessment of serum lipidomic aberrations before type 2 diabetes (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR). RESEARCH DESIGN AND METHODSIn the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score–matched control subjects (n= 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n= 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated. RESULTSAt the level of false-discovery rate <0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)–plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non–PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices. CONCLUSIONSThese findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals. |
| 英文摘要: | OBJECTIVEComprehensive assessment of serum lipidomic aberrations before type 2 diabetes (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR). RESEARCH DESIGN AND METHODSIn the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score–matched control subjects (n= 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n= 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated. RESULTSAt the level of false-discovery rate <0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)–plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non–PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices. CONCLUSIONSThese findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals. |
| 刊物名称: | Diabetes Care |
| 英文刊物名称: | Diabetes Care |
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| 其它备注: | Jieli Lu, Sin Man Lam, Qin Wan, Lixin Shi, Yanan Huo, Lulu Chen, Xulei Tang, Bowen Li, Xueyan Wu, Kui Peng, Mian Li, Shuangyuan Wang, Yu Xu, Min Xu, Yufang Bi, Guang Ning, Guanghou Shui, Weiqing Wang. High-Coverage Targeted Lipidomics Reveals Novel Serum Lipid Predictors and Lipid Pathway Dysregulation Antecedent to Type 2 Diabetes Onset in Normoglycemic Chinese Adults. Diabetes Care. DOI:10.2337/dc19-0100 |
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