347-OR: Plasma Lipidome in People with Insulin-Sensitive and Insulin-Resistant Obesity

Insulin-resistant glucose metabolism is common in obesity. However, some people with obesity are insulin-sensitive. It is not clear whether obesity and insulin sensitivity have independent effects on the plasma lipidome. We evaluated plasma complex lipids (including phospholipids, glycerolipids, sphingolipids, acylcarnitines, and cholesteryl esters) by using UPLC-MS/MS and assessed insulin sensitivity as the glucose disposal rate (GDR) per kg fat-free mass divided by plasma insulin concentration during a hyperinsulinemic-euglycemic clamp procedure in 14 adults with insulin-sensitive obesity [ISO, GDR 99.0 ± 8.1 (mg/kg FFM/min)/(µU/mL), 14 adults with insulin-resistant obesity [IRO, GDR (31.8 ± 1.7 mg/kg FFM/min)/(µU/mL)], and 14 adults who were insulin sensitive and lean [ISL, GDR (101.3 ± 5.5 mg/kg FFM/min)/(µU/mL)]. The ISO and IRO groups were matched on age, sex, and body mass index. A total of 780 lipid species in 15 classes were identified. No plasma lipids were significantly different between the ISL and ISO groups, but 52 lipids were significantly different between the ISO and MUO groups (≥1.25 fold-change and false discovery rate <0.05). For all lipid classes, total concentration (sum of species) was not different between the ISL and ISO groups, whereas phosphatidylethanolamine, phosphatidylglycerol, triglyceride, and diacylglycerol (DAG) concentrations were greater and alkyl-phosphatidylcholine (PC) concentration was lower in the IRO than the ISO group (all P < 0.05). The ten lipid species most strongly correlated with insulin resistance included six DAGs, three sphingomyelins, and one ceramide species (r = -0.55 to -0.66, all P <0.0005). The ten lipids most correlated with insulin sensitivity included five lyso-PC, three alkyl-PC, and two plasmenyl-PC species (r = 0.58 to 0.70, all P <0.0001). These results indicate that insulin resistance, rather than obesity per se, is associated with alterations in the plasma lipidome.