Circulating Palmitoyl Sphingomyelin Is Associated With Cardiovascular Disease in Individuals With Type 2 Diabetes: Findings From the China Da Qing Diabetes Study

OBJECTIVE To investigate the association of potential cardiovascular disease (CVD) biomarkers in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We enrolled 120 participants (aged 61.5–69.5 years) with type 2 diabetes and 60 (aged 62.5–73.5 years) with normal glucose tolerance in the discovery group from the original Da Qing Diabetes Study. Their diabetes status was confirmed in 1986; then, the participants were followed over 23 years to collect CVD outcome data. Untargeted and targeted metabolomics analyses based on ultra-high-performance liquid chromatography–tandem mass spectrometry were used to identify potential markers. Multivariable regression analysis was used to evaluate the association between metabolites and CVD outcomes. An independent group of 335 patients (aged 67.0–77.0 years) with diabetes was used for biomarker validation. RESULTS In the discovery group, untargeted metabolomics analysis found 16 lipids and fatty acids metabolites associated with CVD risk in patients with diabetes, with palmitoyl sphingomyelin (PSM) having the strongest association. Plasma PSM concentrations were significantly higher in cases of diabetes with CVD than without (41.68 ± 10.47 vs. 9.69 ± 1.47 μg/mL; P < 0.0001). The odds ratio (OR) of CVD for 1 µg/mL PSM change was 1.19 (95% CI 1.13–1.25) after adjustment of clinical confounders. The validation study confirmed that PSM was significantly associated with increased CVD risk in diabetes (OR 1.22 [95% CI 1.16–1.30]). CONCLUSIONS Changes in lipid and fatty acid content were significantly associated with CVD risk in the Chinese population with diabetes. PSM is a potential biomarker of increased CVD risk in diabetes.