title: Metabolite Profiling of LADA Challenges the View of a Metabolically Distinct Subtype.
abstract: Latent autoimmune diabetes in adults (LADA) usually refers to GAD65 autoantibodies (GADAb)-positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA from type 1 or type 2 diabetes. In this study, we examined whether metabolite profiling could help to distinguish LADA (n= 50) from type 1 diabetes (n= 50) and type 2 diabetes (n= 50). Of 123 identified metabolites, 99 differed between the diabetes types. However, no unique metabolite profile could be identified for any of the types. Instead, the metabolome varied along a C-peptide-driven continuum from type 1 diabetes via LADA to type 2 diabetes. LADA was more similar to type 2 diabetes than to type 1 diabetes. In a principal component analysis, LADA patients overlapping with type 1 diabetes progressed faster to insulin therapy than those overlapping with type 2 diabetes. In conclusion, we could not find any unique metabolite profile distinguishing LADA from type 1 and type 2 diabetes. Rather, LADA was metabolically an intermediate of type 1 and type 2 diabetes, with those patients closer to the former showing a faster progression to insulin therapy than those closer to the latter.
authors.affiliation: Unit of Molecular Metabolism, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Majdoub
authors.affiliation: Unit of Molecular Metabolism, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.|H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Arslan
authors.initials: A
authors.lastname: Ali
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Storm
authors.affiliation: Translational Diabetes Research, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Rosengren
authors.affiliation: Unit of Molecular Metabolism, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.|Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Helsinki, Finland.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Unit of Molecular Metabolism, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden peter.spegel@chem.lu.se.|Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Spégel
mesh_terms: D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D000071698:Latent Autoimmune Diabetes in Adults / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D025341:Principal Component Analysis; D013548:Sweden; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human; C401141:glutamate decarboxylase 2