Metabolite Profiling of LADA Challenges the View of a Metabolically Distinct Subtype

Diabetes. 2017 Apr;66(4):806-814. doi: 10.2337/db16-0779. Epub 2016 Dec 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Autoantibodies / immunology
  • Blood Glucose / metabolism
  • C-Peptide / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Disease Progression
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Latent Autoimmune Diabetes in Adults / drug therapy
  • Latent Autoimmune Diabetes in Adults / immunology
  • Latent Autoimmune Diabetes in Adults / metabolism*
  • Male
  • Metabolome*
  • Middle Aged
  • Principal Component Analysis
  • Sweden
  • Young Adult

Substances

  • Autoantibodies
  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2