TY - JOUR
T1 - Impact of long-term poor and good glycemic control on metabolomics alterations in type 1 diabetic people
AU - Dutta, Tumpa
AU - Kudva, Yogish C.
AU - Persson, Xuan Mai T.
AU - Schenck, Louis A.
AU - Charles Ford, G.
AU - Singh, Ravinder J.
AU - Carter, Rickey
AU - Sreekumaran Nair, K.
N1 - Funding Information:
We acknowledge the nursing and laboratory staff of the Clinical Research Unit and Mayo Clinic Metabolomics Resource Core. Address all correspondence and requests for reprints to: Sreekumaran Nair, MD, PhD, Division of Endocrinology and Metabolism, Mayo Clinic, 200 First Street SW, Joseph 5-194, Rochester, MN 55905. E-mail: nair.sree@mayo.edu. This work was supported by National Institutes of Health Grants R01 DK41973, U24 DK100469, and UL1 TR000135 as well as the David Murdock Dole Professorship. Disclosure Summary: The authors have nothing to disclose.
PY - 2016/3
Y1 - 2016/3
N2 - Context: 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. Objective: 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. Design:Wecompared plasma metabolites in T1D with poor (glycated hemoglobin≥8.5%, T1D[≥] and good (glycated hemoglobin<6.5%, T1D[+]) glycemic control with nondiabetic controls (ND). Setting: The study was conducted at the clinical research unit. Patients or Other Participants: T1D with poor (n=14), T1D(≥) and good, T1D(+) (n=15) glycemic controlandmatched(for age, sex,andbodymass index)NDparticipantswereincluded in the study. Intervention(s): There were no intervention. Main Outcome Measure(s): Comparison of qualitative and quantitative profiling of metabolome was performed. Results: 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, branchchain 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. Conclusions: 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.
AB - Context: 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. Objective: 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. Design:Wecompared plasma metabolites in T1D with poor (glycated hemoglobin≥8.5%, T1D[≥] and good (glycated hemoglobin<6.5%, T1D[+]) glycemic control with nondiabetic controls (ND). Setting: The study was conducted at the clinical research unit. Patients or Other Participants: T1D with poor (n=14), T1D(≥) and good, T1D(+) (n=15) glycemic controlandmatched(for age, sex,andbodymass index)NDparticipantswereincluded in the study. Intervention(s): There were no intervention. Main Outcome Measure(s): Comparison of qualitative and quantitative profiling of metabolome was performed. Results: 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, branchchain 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. Conclusions: 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.
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U2 - 10.1210/jc.2015-2640
DO - 10.1210/jc.2015-2640
M3 - Article
C2 - 26796761
AN - SCOPUS:84960887455
VL - 101
SP - 1023
EP - 1033
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -