Jieli Lu1, Sin Man Lam2, Qin Wan3, Lixin Shi4, Yanan Huo5, Lulu Chen6, Xulei Tang7, Bowen Li2, Xueyan Wu1, Kui Peng1, Mian Li1, Shuangyuan Wang1, Yu Xu1, Min Xu1, Yufang Bi1, Guang Ning1, Guanghou Shui8, Weiqing Wang9. 1. Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commision of the People's Republic of China, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China. 2. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. 3. Affiliated Hospital of Southwest Medical University, Luzhou, China. 4. Affiliated Hospital of Guiyang Medical College, Guiyang, China. 5. Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China. 6. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 7. The First Hospital of Lanzhou University, Lanzhou, China. 8. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China wqingw61@163.com ghshui@genetics.ac.cn. 9. Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commision of the People's Republic of China, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China wqingw61@163.com ghshui@genetics.ac.cn.
Abstract
OBJECTIVE: Comprehensive assessment of serum lipidomic aberrations before type 2 diabetes mellitus (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 METHODS: In 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. RESULTS: At 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. CONCLUSIONS: These 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.
OBJECTIVE: Comprehensive assessment of serum lipidomic aberrations before type 2 diabetes mellitus (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 METHODS: In 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. RESULTS: At 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. CONCLUSIONS: These 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.
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