title: The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus.
abstract: Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD)--compared with single and low-titre autoantibody--is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups.
authors.affiliation: Department of Endocrinology/Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: van Deutekom
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
authors.forename: S
authors.initials: S
authors.lastname: Simsek
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D005968:Glutamate Decarboxylase