title: Specific Metabolic Profiles and Their Relationship to Insulin Resistance in Recent-Onset Type 1 and Type 2 Diabetes.
abstract: Insulin resistance reflects the inadequate insulin-mediated use of metabolites and predicts type 2 diabetes (T2D) but is also frequently seen in long-standing type 1 diabetes (T1D) and represents a major cardiovascular risk factor.
  
  
  
  We hypothesized that plasma metabolome profiles allow the identification of unique and common early biomarkers of insulin resistance in both diabetes types.
  
  
  
  Two hundred ninety-five plasma metabolites were analyzed by mass spectrometry from patients of the prospective observational German Diabetes Study with T2D (n = 244) or T1D (n = 127) and known diabetes duration of less than 1 year and glucose-tolerant persons (CON; n = 129). Abundance of metabolites was tested for association with insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamps and related metabolic phenotypes.
  
  
  
  Sixty-two metabolites with phenotype-specific patterns were identified using age, sex, and body mass index as covariates.
  
  
  
  Compared with CON, the metabolome of T2D and T1D showed similar alterations in various phosphatidylcholine species and amino acids. Only T2D exhibited differences in free fatty acids compared with CON. Pairwise comparison of metabolites revealed alterations of 28 and 49 metabolites in T1D and T2D, respectively, when compared with CON. Eleven metabolites allowed differentiation between both diabetes types and alanine, α-amino-adipic acid, isoleucin, and stearic acid showed an inverse association with insulin sensitivity in both T2D and T1D combined.
  
  
  
  Metabolome analyses from recent-onset T2D and T1D patients enables identification of defined diabetes type-specific differences and detection of biomarkers of insulin sensitivity. These analyses may help to identify novel clinical subphenotypes diabetes.
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Birgit
authors.initials: B
authors.lastname: Knebel
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strassburger
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Jorg
authors.initials: J
authors.lastname: Kotzka
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Marsel
authors.initials: M
authors.lastname: Scheer
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Karsten
authors.initials: K
authors.lastname: Müssig
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehr
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Helmut
authors.initials: H
authors.lastname: Finner
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Birgit
authors.initials: B
authors.lastname: Klüppelholz
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Giani
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Hadi
authors.initials: H
authors.lastname: Al-Hasani
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry (B.Kn., J.K., S.L., H.-A.H.), Institute for Biometrics and Epidemiology (K.S., M.S., H.F., B.Kl., G.G.), Institute for Clinical Diabetology (J.S., B.N., K.M., M.R.), German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology (J.S., B.N., K.M., M.R.), Medical Faculty, Heinrich Heine University 40225 Duesseldorf, Germany; German Center for Diabetes Research (B.Kn., K.S., J.S., J.K., M.S., B.N., K.M., S.L., H.F., B.Kl., G.G., H.-A.H., M.R.), 85764 Muenchen-Neuherberg, Germany; and Metabolic Unit (G.P.), Institute of Neuroscience, Research Program on Aging of the Italian Research Council, 35127 Padua, Italy.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000596:Amino Acids; D005230:Fatty Acids, Nonesterified