1620-P: Metabolites Associated with Insulin Resistance in Women with and without Type 1 Diabetes

Abstract

Having type 1 diabetes (T1D) at least doubles insulin resistance (IR) compared to people without diabetes, but factors explaining this increased IR remain poorly understood. We analyzed untargeted plasma metabolomics in 30 premenopausal women aged 18-45 years (15 with and 15 without T1D) who underwent a hyperinsulinemic euglycemic clamp to measure insulin sensitivity. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was used to identify metabolites that discriminated T1D status and diabetes-specific GIR tertile. Women with T1D had a significantly lower glucose infusion rate (GIR) than women without diabetes (5.5 ± 3.2 mg/kg/min vs. 12.8 ± 5.4 mg/kg/min, p=0.0001), indicating lower insulin sensitivity. Using sPLS-DA, we identified two components that discriminated T1D status (AUC=0.84) and two components that discriminated the lowest vs. highest group-specific GIR tertile (AUC= 0.91). Metabolite pathways discriminating T1D status and lowest vs. highest GIR tertile are shown in the Table. Common pathways discriminating both T1D and GIR tertile are in bold in the Table. Plasma metabolites mainly in the amino acid and lipid metabolism pathways differed by T1D status, and both overlapping and novel metabolites distinguished IR in premenopausal women. These data provide insight into common factors influencing IR regardless of diabetes status, as well as metabolic pathways affected by T1D. Disclosure J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. I.E. Schauer: None. B.C. Bergman: Consultant; Spouse/Partner; Novo Nordisk Inc., Sanofi US. Research Support; Self; Eli Lilly and Company. Speaker’s Bureau; Spouse/Partner; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. K.J. Nadeau: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. A. Keshawarz: None. L. Pyle: None. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.)