Omics based methods may provide new markers associated to diabetic retinopathy (DR). We investigated a wide omics panel of metabolites and lipids related to DR in type 1 diabetes. Metabolomic analyses were performed using two-dimensional gas chromatography with time-of-flight mass spectrometry and lipidomic analyses utilizing an ultra-high-performance liquid chromatography quadruple time-of-flight mass spectrometry method in 648 individuals with type 1 diabetes. Subjects were sub-divided into: no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR. Endpoints were any progression of DR, onset of DR and progression from mild to severe DR tracked from standard ambulatory care and investigated using Cox models. The cohort consisted of 648 participants aged mean 54.4±12.8 years, 55.5% were male, and follow-up was 5.1-5.5 years. Cross-sectionally, 2,4-dihydroxybutyric acid (DHBA), 3,4-DHBA, ribonic acid, ribitol, and the triglycerides 50:1 and 50:2 significantly correlated (p<0.042) to DR stage. Longitudinally, higher 3,4-DHBA was a risk marker for progression of DR (n=133) after adjustment (p=0.033). We demonstrated multiple metabolites being positively correlated to higher grade of DR in type 1 diabetes, and several triglycerides being negatively correlated. Furthermore, higher 3,4-DHBA was an independent risk marker for progression of DR, however, confirmation is required.© 2020 by the American Diabetes Association.