Determining the Effect of Disrupted Lipid Metabolism on Increasing Cardiovascular Risk in Diabetes Patients with UHPLC–MS/MS

Lipidomic analysis using ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC–MS/MS) was performed to examine specific lipid species associated with subclinical carotid atherosclerosis (SCA) presence and burden in a population of individuals with type 1 (T1D) and type 2 (T2D) diabetes, as well as a control group of subjects without diabetes. Using contrast analysis, the research team uncovered risk-specific lipidic patterns associated with SCA, such as habitual smoking, hypertension, and dyslipidemia. A paper based on this work was published in Cardiovascular Diabetology (1).

Cardiovascular (CV) disease is the leading cause of death globally, with atherosclerosis being its primary underlying factor (2). Important risk factors for CV disease, T1D and T2D are associated with accelerated atherosclerosis and a higher incidence of CV complications (3). While the risk of CV death is twofold higher in subjects with T2D (4), and up to four times greater in subjects with T1D (5), the fundamental molecular mechanisms connecting diabetes with advanced atherosclerosis are not completely understood (3). Additionally, in a T2D population, the Framingham risk score has been revealed to underestimate the CV risk (6), while the United Kingdom Prospective Diabetes Study score indicates an overestimation of the risk of CV (7). Furthermore, SCA has a higher predictive power than that of classic CV risk factors and including it in CV risk equations improves the overall performance of risk prediction (8).

Crucial for cell function, lipids serve a great variety of functions (9). While disorders in the composition of cell lipids may be related to atherosclerosis, conventional lipid biomarkers (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]) may not reflect the complicated alteration of lipid metabolism in diabetes driving the risk of CV risk disease (1). Lipidomics offers a robust, unique platform for discovering new lipid biomarkers connected with CV disease (10). Lipid species and classes are associated with T1D (11,12) and T2D (11,13), coronary heart disease (14), acute or stable arterial disease, and other CV events (15). Therefore, the researchers believe that lipids could provide biomarkers useful in the diagnosis of SCA (1).

A total of 513 subjects (151 T1D, 155 T2D, and 207 non-diabetic control) were included in the study; the percentage of subjects with SCA was 48.3%, 49.7%, and 46.9%, respectively. A total of 27 unique lipid species were associated with SCA in subjects with T2D, in former or current smokers with T2D, and in individuals with T2D without dyslipidemia. Phosphatidylcholines and diacylglycerols were the main SCA-associated lipidic classes. Ten different species of phosphatidylcholines were up-regulated, while four phosphatidylcholines containing polyunsaturated fatty acids were down-regulated. One diacylglycerol was downregulated, while the other three were positively associated with SCA in individuals with T2D without dyslipidemia. The researchers discovered several features significantly associated with SCA in individuals with T1D, but only one sterol could be partially annotated (1).

The authors of the paper state that this is the first study to reveal specific lipids significantly associated with SCA in subjects with T1D, T2D, and without diabetes without known previous CV events, together with risk factors-specific lipid differences associated with SCA. Furthermore, they report the demonstration of greater SCA-related disruption in lipid metabolism in subjects with T2D compared to those with T1D or without diabetes, as well as more pronounced disruption in former or current smokers and individuals not undergoing lipid-lowering treatment. They believe that these findings demonstrate the power of lipidomics to discover new biomarkers for preventive medicine in cardiovascular research. Validating the annotated lipids found in this work in an independent cohort, however, is required to confirm them as potential SCA biomarkers (1).

Cardiologist checks heart rate of older male patient for coronary artery disease prevention. © fizkes - stock.adobe.com

References

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