THU586 Lipid Species In Non-alcoholic Fatty Liver Disease (NAFLD) In Type 1 Diabetes
Authors: Taiwo Adeyinka , Thakker Himani , Maschek John , Cox James , Summers Scott , Jalal Diana , Sivitz William , Dokun Ayotunde , Chaurasia Bhagirath 
Published: October 2023

Disclosure: A. Taiwo: None. H. Thakker: None. J. Maschek: None. J. Cox: None. S. Summers: Owner/Co-Owner; Self; Centaurus Therapeutics. D. Jalal: None. W. Sivitz: None. A. Dokun: None. B. Chaurasia: None.

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis at an early stage, which can progress over the years to nonalcoholic steatohepatitis (NASH) and cirrhosis. Steatosis is composed of various lipid species which is derived from influx of monounsaturated and polyunsaturated fatty acids, saturated fats, into the liver caused by peripheral lipolysis in adipocytes and de novo lipogenesis. It is estimated that 20-30% patients with NAFLD will progress to NASH. Hepatic lipotoxicity and inflammation are two key factors that drive the progression of NAFLD to NASH. The presence of NASH increases the risk of cardiovascular events, cirrhosis, hepatocellular cancer and non-liver malignancies. Objective: To determine the association of lipid species with NAFLD in individuals with Type 1 diabetes. Study Design: Thirty individuals with Type 1 diabetes were recruited from our diabetes Clinic at University of Iowa Hospital & Clinics. Participants in this cross-sectional study were categorized into two groups based on the results of a FibroScan, an elastography technique that quantifies liver fat and stiffness. Classification as cases (n = 16) or controls (n = 14) was assigned based on the presence or absence of evidence for NAFLD respectively. The participants came in for a single visit where fasting plasma was drawn for lipidomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total thirty-three lipid species belonging to four different lipid classes: sphingolipids (dihydroceramides, ceramides, dihydrosphingomyelin, sphingomyelin, hexosylceramide), diacylglycerol, phosphatidylcholine and triacylglycerols were analyzed via targeted lipidomics. Results: The BMI was significantly higher in the cases than controls (P = 0.002) and the cases used significantly higher 24 hr insulin doses than controls (P = 0.004). The cases displayed significantly higher circulating levels of total ceramides (p=0.02), diacylglycerol (P= 0.0003) and triacylglycerols (P=0.0003). The two groups displayed similar levels of hexosylceramide, dihydrosphingomyelin, sphingomyelin and phosphatidylcholine. Similar to previous findings numerous sphingolipid species, diacylglycerol and triacylglycerols were found to be positively correlated with BMI. In addition, they were found to be positively correlated with 24hrs insulin dose. Importantly, total circulating dihydroceramide, ceramide, diacylglycerol and triacylglycerols levels were significantly corelated with steatosis score (P = &lt;0.05). None of the lipid species correlated with the fibrosis score. Conclusion: These results suggest that Type 1 diabetes individuals with NAFLD have a higher BMI and display elevated circulating levels of dihydroceramides, ceramides, diacylglycerol and triacylglycerols that are strongly associated with the development of fatty liver disease.

Presentation: Thursday, June 15, 2023