UCSF

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 (MASALA) 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) (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.

Conclusions

Three circulating ceramides were strongly associated with NAFLD and fasting glucose after 5 years, and partially mediated this association.