Ceramides as risk markers for future cardiovascular events and all-cause mortality in long-standing type 1 diabetes

Background: Ceramides are lipid molecules involved in inflammation-related signaling. Recent studies have shown that higher amounts of specific circulating ceramides and ceramide ratios are associated with future development of cardiovascular (CV) disease (CVD). In persons with longstanding type 1 diabetes (T1D), we investigated if serum ceramide levels and ratios predicted CVD, kidney failure and all-cause mortality. Methods: We included 662 participants with T1D from 2009-2011. Health registry data was obtained at a 6-year follow-up. Baseline serum samples were analyzed using liquid chromatography-mass spectrometry. Six predefined ceramide levels were measured and ratios calculated. Adjusted Cox regression analyses were carried out to investigate ceramide levels in relation to future CV events (CVE), kidney failure and all-cause mortality. Results: Ceramide ratio cer(d18:1/18:0)/cer(d18:1/24:0) was significantly associated with risk of CVE (HR = 1.33, P = 0.01) and all-cause mortality (HR = 1,48, P = 0.01) before and after adjustments. All five investigated ceramide ratios were associated with kidney failure, before adjusting for the kidney markers estimated glomerular filtration rate and urinary albumin excretion rate. Conclusions: Specific ceramides and ratios associated with 6-year cardiovascular risk and all-cause mortality in a T1D cohort. The ratio of cer(d18:1/18:0)/cer(d18:1/24:0) was an especially robust indicator. This highlights the strength of ceramide association with vascular complications and presents a new potential tool for early risk assessment if validated in other cohorts. Trial Registration: ClinicalTrial.gov identifier: NCT01171248