Plasma Lipidomic Profiling and Risk of Type 2 Diabetes in the PREDIMED Trial

Abstract

Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend £0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk. Type 2 diabetes (T2D), which results from insulin resistance and inadequate compensatory insulin secretion (1,2), currently has a global prevalence of 9%, which is projected to rise to 10.4% (642 million cases) by 2040 (3). Dyslipidemia, characterized by a high plasma triglyceride concentration, low HDL cholesterol concentration, and increased concentration of small dense LDL cholesterol particles, is usually present in T2D (4,5). Triglycerides encompass a large number of individual molecular species, whereas lipoproteins include many different lipid classes containing multiple molecular species (6). The role that these individual

Postprandial Metabolism is Impaired in Overweight Normoglycemic Young Adults without Family History of Diabetes

“…A large number of metabolomics studies have been conducted in patients with T2DM [24][25][26][27][28] . Metabolomics analysis has, however, not been widely used to identify altered metabolism in healthy people who are at risk for T2DM 6,29 .…”

“…Metabolomics analysis has, however, not been widely used to identify altered metabolism in healthy people who are at risk for T2DM 6,29 . A Chinese cohort study and PREDIMED trial had employed targeted metabolomics 24,27 . A recent report of the PREDIMED Trial study indicates a non-targeted metabolomics approach.…”

Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women

“…Besides the function of membrane phospholipid metabolites, their role as intracellular signal molecules is increasingly appreciated, including regulating cellular proliferation, inflammation, and tumor cell invasion (6,7). Increasing evidence suggests that abnormal LPC levels are associated with many diseases, including diabetes, cardiovascular diseases, and cancers (8)(9)(10). However, findings from those lipidomics studies were inconsistent.…”

Lipidomics Identified Lyso-phosphatidylcholine&nbsp;and Phosphatidylethanolamine&nbsp;as Novel&nbsp;Biomarkers for Diagnosis of Laryngeal Cancer

“…Lipidomics, focusing on comprehensive pro ling of lipids in complex biological matrice, is a powerful tool to identify disease-related lipid biomarkers, and to explore disordered lipid metabolism in the development of diseases. It has been widely applied in many studies, such as diabetes [4,5], lung cancer [6], liver cancer [7,8], and so on. Unfortunately, no laryngeal cancer-associate lipidomic study has yet been performed.…”