Associations of NAFLD with circulating ceramides and impaired glycemia. (April 2022)

• Record Type: Journal Article
• Authors: Gadgil, Meghana D.; Sarkar, Monika; Sands, Caroline; Lewis, Matthew R.; Herrington, David M.; Kanaya, Alka M.
• Is Part Of: Diabetes research and clinical practice. Volume 186(2022)
• Publication Date: 2022-04
• Subjects: Ceramides -- NAFLD -- South Asian -- Type 2 diabetes; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2022.109829
• Languages: English
• ISSNs: 0168-8227

Abstract

Abstract: 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.