1349-P: Bariatric Surgery Causes an Early Improvement in the Lipidomic Profile and a Decrease in Plasma Ceramides and Diacylglycerols in Patients with Type 2 Diabetes and NAFLD

Abstract

Bariatric surgery (BarS) is known to improve insulin resistance (IR) , atherogenic dyslipidemia and steatohepatitis in patients (pts) with type 2 diabetes (T2D) . Total ceramides (Cer) and diacylglycerols (DAGs) have been implicated in the development of IR and nonalcoholic fatty liver disease (NAFLD) , but the impact of BarS on their plasma concentration remains unclear. The aim of this study was to assess early changes in the plasma lipidome, before and 3-6 months post BarS. To this end, we recruited 17 pts with NAFLD who underwent BarS (age 47±3, BMI 46±2 kg/m2, 76% with T2D) , and 6 controls without T2D (baseline data only, age 47±6, BMI 31.2±2.1 kg/m2) . Global lipidomic profiling was performed on orbitrap mass spectrometer with UHPLC. Data was analysed using LipidMatch software. Plasma levels of total lipids (TL) (34%; p=0.01) , Cer (20%; p=0.31) , DAGs (50%; p=0.03) and total triglycerides (TG) (79%; p=0.01) were higher in pts with NAFLD compared to controls. Bariatric surgery reduced plasma TL (-26%) , Cer (-31%) , DAGs (-34%) and TG (-43%) levels (all p<0.01) . In pts with vs. without T2D, plasma TL were higher (28%; p=0.01) . There was a reduction in TL (-29%; p<0.01) , Cer (-22%; 0.27) , DAGs (-41%; p=0.02) and TG (-52%; p<0.01) post BarS and a similar pattern was observed across the lipidomic profile (cholesterol esters, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol) . Reduction in weight after BarS correlated with lower DAGs (r=0.81; p=0.03) and TG (r=0.66; p=0.07) . Reduction in Cer correlated with improved HOMA-IR (r= 0.71; p=0.04) and Adipo-IR (r= 0.63; p=0.09) . In conclusion, pts with NAFLD and T2D have a significantly worse lipidomic profile compared to pts without T2D. The unfavorable lipidomic profile was normalized after BarS, in particular Cer and DAG levels, known to be linked to IR. Assessment of the lipidomic profile may provide further insights into insulin sensitivity changes after BarS. Disclosure S.Kalavalapalli: None. A.Zarrinpar: None. K.Cusi: Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Fractyl Health, Inc., Genentech, Inc., Hanmi Pharm. Co., Ltd., Intercept Pharmaceuticals, Inc., Novo Nordisk. D.Barb: None. R.E.Dillard: None. E.Godinez: None. J.Friedman: n/a. N.Fanous: None. C.O.Warren: None. F.Bril: None. R.Lomonaco: None.