Associations of NAFLD with circulating ceramides and impaired glycemia

Aim: Determine the association of circulating ceramides with NAFLD and glycemic impairment. Methods: Sample: 669 participants in the Mediators of Atherosclerosis in South Asians Living in America (MA-SALA) cohort aged 40-84 years without cardiovascular disease, cirrhosis, or significant alcohol intake. Clinical measures: Computed 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 analysis: Linear 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. Results: Average 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) (beta -4.29; 95% CI [-5.98, -2.59]) and (beta -3.40; 95% CI [-5.11, -1.70]), and LacCer(d18:1/ 16:0) with higher attenuation (beta 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. Conclusions: Three circulating ceramides were strongly associated with NAFLD and fasting glucose after 5 years, and partially mediated this association.

Automated summary

The study found that three circulating ceramides were strongly associated with NAFLD and fasting glucose after 5 years, and partially mediated this association.