Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes

Background Type 2 diabetes is a common disease around the world and its major complications are diabetic retinopathy (DR) and diabetic kidney disease (DKD). Persons with type 2 diabetes with complications, especially who have both DR and DKD, have poorer prognoses than those without complications. Therefore, prevention and early identification of the complications of type 2 diabetes are necessary to improve the prognosis of persons with type 2 diabetes. The aim of this study is to identify factors associated with the development of multiple complications of type 2 diabetes. Methods We profiled serum metabolites of persons with type 2 diabetes with both DR and DKD ( N = 141) and without complications ( N = 159) using a comprehensive non-targeted metabolomics approach with mass spectrometry. Based on the serum metabolite profiles, case–control comparisons and metabolite set enrichment analysis (MSEA) were performed. Results Here we show that five metabolites (cyclohexylamine, P = 4.5 × 10 −6 ; 1,2-distearoyl-glycero-3-phosphocholine, P = 7.3 × 10 −6 ; piperidine, P = 4.8 × 10 −4 ; N -acetylneuraminic acid, P = 5.1 × 10 −4 ; stearoyl ethanolamide, P = 6.8 × 10 −4 ) are significantly increased in those with the complications. MSEA identifies fatty acid biosynthesis as the type 2 diabetes complications-associated biological pathway ( P = 0.0020). Conclusions Our metabolome analysis identifies the serum metabolite features of the persons with type 2 diabetes with multiple complications, which could potentially be used as biomarkers. Plain language summary In the management of type 2 diabetes, prevention and early identification of diabetes complications are important. In particular, people with type 2 diabetes with diabetic retinopathy (DR), affecting the eye, and diabetic kidney disease (DKD), have poorer outcomes than those without complications and need early intervention. Here, we comprehensively profiled blood metabolites, or breakdown products of the biological processes occurring in the body, of people with type 2 diabetes with both DR and DKD and those without complications. We found that five metabolites were significantly increased in those with complications, and we identified a specific metabolic pathway associated with having complications. Our analysis identified the blood metabolite features of people with type 2 diabetes with multiple complications, which could potentially be used as markers in the future. Tomofuji et al. perform non-targ