Impact of Long-Term Poor and Good Glycemic Control on Metabolomics Alterations in Type 1 Diabetic People.

Abstract

Poor glycemic control in individuals with type 1 diabetes (T1D) is associated with both micro- and macrovascular complications, but good glycemic control does not fully prevent the risk of these complications. The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control. We compared plasma metabolites in T1D with poor (glycated hemoglobin ≥ 8.5%, T1D[-] and good (glycated hemoglobin < 6.5%, T1D[+]) glycemic control with nondiabetic controls (ND). The study was conducted at the clinical research unit. T1D with poor (n = 14), T1D(-) and good, T1D(+) (n = 15) glycemic control and matched (for age, sex, and body mass index) ND participants were included in the study. There were no intervention. Comparison of qualitative and quantitative profiling of metabolome was performed. In T1D(-), 347 known metabolites belonging to 38 metabolic pathways involved in cholesterol, vitamin D, tRNA, amino acids (AAs), bile acids, urea, tricarboxylic acid cycle, immune response, and eicosanoids were different from ND. In T1D(+),154 known metabolites belonging to 26 pathways including glycolysis, gluconeogenesis, bile acids, tRNA biosynthesis, AAs, branch-chain AAs, retinol, and vitamin D metabolism remained altered from ND. Targeted measurements of AA metabolites, trichloroacetic acid, and free fatty acids showed directional changes similar to the untargeted metabolomics approach. Comprehensive metabolomic profiling identified extensive metabolomic abnormalities in T1D with poor glycemic control. Chronic good glycemic control failed to normalize many of these perturbations, suggesting a potential role for these persistent abnormalities in many complications in T1D.