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

Abstract

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.

Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy

“…They compared the abundance of 364 serum metabolites between patients with T2D and with both DR and DKD (N = 141) and those without one of DR or DKD (N = 159). Interestingly, they evidenced N-acetylneuraminic acid, which is a major form of sialic acid in humans, as a relevant biomarker in T2D patients with both retinal and renal complications [47], which is consistent with our results.…”

Common metabolite for microangiopathy in Japanese and European populations

“…Tomofuji et al 2 . revealed the serum metabolite signatures of persons with type 2 diabetes mellitus with both diabetic retinopathy (DR) and diabetic kidney diseases (DKD) using a comprehensive untargeted metabolomics approach combining capillary electrophoresis time‐of‐flight mass spectrometry (CU‐TOFMS) and liquid chromatography TOFMS 2 .…”

“…Tomofuji et al . 2 revealed the serum metabolite signatures of persons with type 2 diabetes mellitus with both diabetic retinopathy (DR) and diabetic kidney diseases (DKD) using a comprehensive untargeted metabolomics approach combining capillary electrophoresis time‐of‐flight mass spectrometry (CU‐TOFMS) and liquid chromatography TOFMS 2 . They compared the abundance of 364 metabolites between persons with type 2 diabetes mellitus with both DR and DKD ( N = 141) and those without either DR or DKD ( N = 159).…”

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

“…Low circulating plasma levels of tyrosine and alanine were identified as markers for microvascular risk in T2D individuals, while decreased leucine, histidine, and valine correlated with higher mortality risk [ 230 ]. Fatty acid biosynthesis was associated with T2D complications, and specific metabolites were found to be elevated in patients with both retinal and renal complications of T2D [ 231 ].…”