Ceramides recently have attracted interest as a marker of cardiovascular event risk. However, only little is known about their role in the development of type 2 diabetes (T2DM). We analyzed the ceramide ratio Cer d18:18/Cer d 18:24:0 (CerRatio) in 894 consecutive Caucasian patients who were referred to angiography for the evaluation of established or suspected stable coronary artery disease (CAD). T2DM was diagnosed according to ADA criteria. The incidence of T2DM was recorded over a follow-up time of up to 16 years (median: 13 [8-14] years). At baseline, the CerRatio was significantly higher in T2DM (n=239) than in nondiabetic patients (4.6e-2 vs. 3.9e-2, p<0.001). During follow-up, diabetes was newly diagnosed in 71 patients, i.e. in 11% of the initially nondiabetic subjects. The CerRatio strongly predicted the incidence of T2DM both univariately (standardized OR 1.47 [1.11-1.96]; p=0.008) and in a multivariately adjusted model (figure) comprising age, sex, BMI, the presence of significant CAD at angiography, and hemoglobin A1c (HbA1c; OR=1.45 [1.07-1.98]; p=0.018). Though the CerRatio was significantly correlated with BMI (r=0.138, p<0.001) and HbA1c (r=0.137, p<0.001), applying a mediation analysis revealed that BMI and HbA1c had only marginal indirect effects (5, 7% and 3.6%, respectively) on the association of the CerRatio with T2DM incidence. We conclude that ceramides strongly and independently predict the development of diabetes.


A. Leiherer: None. A. Muendlein: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. P. Fraunberger: None. H. Drexel: None. C.H. Saely: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.