THU585 Non-alcoholic Fatty Liver Disease (NAFLD), A Silent But Emerging Problem In Type 1 Diabetes

Abstract

Abstract Disclosure: A. Taiwo: None. R. Merill: None. L. Wendt: None. D. Pape: None. H. Thakker: None. N. Pothireddy: None. B. Carlson: None. A. Sanchez: None. P. Ten Eyck: None. D. Jalal: None. A. Dokun: None. E. Taylor: None. W. Sivitz: None. Background: Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Risk factors include type 2 diabetes, insulin resistance and obesity. Although NAFLD has been widely studied in persons with type 2 diabetes, far less in known about the pathogenesis and severity of NAFLD in type 1 diabetes. Objective: The goal of this study was to understand the metabolic perturbations that contribute to the pathogenesis of NAFLD in type 1 diabetes. Study Design: We conducted a cross-sectional study of 30 participants with type1 diabetes recruited from our institutional diabetes clinic. To assess liver fat content and stiffness, a FibroScan was done. Based on the results, participants were stratified into a case group (evidence of NAFLD) or control group (no evidence of NAFLD). All participants had fasting plasma drawn to determine metabolites. Gas-Chromatography Mass Spectrometry was used for metabolomic analyses and Liquid Chromatography Mass Spectrometry for lipidomic and acylcarnitines analyses. Results: Sixteen of 30 participants were classified as cases and 14 as controls. Cases had higher BMI (P=0.001) and were taking higher daily insulin doses than controls (P=0.008). Metabolomic analyses revealed that cases had elevated levels of glutamate (P=0.001), alanine (P=<0.001), pyruvate (P=<0.001), phenylalanine (P = 0.005), lactate (P=0.019) and anthranilic acid (P=0.029). Lipidomics revealed that, cases had elevated ceramides (P= 0.02), diacylglycerol (P=0.0003) and triacylglycerol (P=0.0003). The acylcarnitine, isovalerylcarnitine (CAR.5.0) a metabolite of isoleucine catabolism, was elevated in the cases (P = 0.010). Pathway enrichment analysis revealed, phenylalanine and tyrosine metabolism, tryptophan metabolism, glucose-alanine cycle, glutamate metabolism and glutathione metabolism were significantly enriched in the cases. Conclusion: We observed evidence of elevated metabolite levels involved in gluconeogenesis, glucose-alanine metabolism, energy metabolism, insulin resistance, and dysfunctional fat synthesis in the cases compared to controls. Our cases had some features similar to Type 2 diabetes with NAFLD, with evidence of elevated levels of aromatic amino acids, ceramides, diacylglycerol and triacylglycerol. However unlike Type 2 diabetes, there was no elevation of branched-chain amino acids levels. Presentation: Thursday, June 15, 2023