Association between specific plasma ceramides and high-sensitivity C-reactive protein levels in postmenopausal women with type 2 diabetes

AIM: Emerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, only scanty information is currently available on the association between distinct plasma ceramides (those associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group at high risk of developing CVD and other chronic inflammation-related conditions. METHODS: Previously, six high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] were identified in 92 postmenopausal women with T2DM attending a diabetes outpatients service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. RESULTS: Plasma hs-CRP levels were positively associated with all measured ceramides on univariable linear regression analyses, but only plasma Cer(d18:1/16:0) (standard β coefficient: 0.27, P = 0.015), Cer(d18:1/22:0) (standard β coefficient: 0.25, P = 0.032) and Cer(d18:1/24:1) (standard β coefficient: 0.30, P = 0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs. CONCLUSION: In postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors.