Associations of NAFLD with circulating ceramides and impaired glycemia

Abstract

AimDetermine the association of circulating ceramides with NAFLD and glycemic impairment. MethodsSample: 669 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort aged 40–84 years without cardiovascular disease, cirrhosis, or significant alcohol intake. Clinical measuresComputed tomography scans at baseline for hepatic attenuation. Fasting serum specimens at baseline and after 5 years. Lipidomics: LC-MS-based analysis of 19 known ceramide signals. Statistical analysisLinear and logistic regression models of log-transformed ceramides, hepatic attenuation and glucose adjusted for age, sex, calories, study site, BMI, exercise, diet quality, alcohol, saturated fat, lipid-lowering medications and fasting glucose. ResultsAverage age was 55 years, 44% were women, mean BMI was 25.9 kg/m2, and 8% had NAFLD. In adjusted models, Cer(d16:1/20:0) and Cer(d18:1/18:0) were associated with lower mean hepatic attenuation (increased liver fat) (β −4.29; 95% CI [-5.98, −2.59]) and (β −3.40; 95% CI [-5.11, −1.70]), and LacCer(d18:1/16:0) with higher attenuation (β 4.44; 95% CI [2.15, 6.73]). All three ceramides partially mediated the relationship between hepatic attenuation and fasting glucose by 16%, 11% and 5%, respectively, after 5-years. ConclusionsThree circulating ceramides were strongly associated with NAFLD and fasting glucose after 5 years, and partially mediated this association.