title: Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus in women.
abstract: Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes mellitus (IDDM) are less well characterized in adults than in children. We quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared frequencies and levels in 139 Finnish women from whom 390 serum samples had been archived during antecedent pregnancies for 10 years before and up to 1 year after diagnosis of diabetes. Also, we compared the autoantibody status in adults with IDDM with that of children with newly diagnosed IDDM. Of the 35 women seropositive for 1 or more autoantibodies, 77% developed IDDM, 11% non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), 9% gestational diabetes mellitus requiring insulin (GDM-ins) and 3% GDM controlled by diet. The frequency of antibodies during the 10-year presymptomatic period was 83% for anti-glutamic acid decarboxylase (GAD), 52% for anti-ICA512 and 41% for islet cell antibodies (ICA) for those who developed IDDM, 25%, 17%, and 0% for NIDDM, 12%, 4%, and 8% for GDM-ins and 1%, 0%, and 1% for GDM-diet. Anti-GAD was found most consistently in early samples; 13 of 15 with a single autoantibody at their first test had anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant, anti-ICA512 increased threefold, and ICA increased slightly before diagnosis. Levels of the autoantibodies varied between subjects, but were relatively stable in individual subjects. Comparison of tests on the women, and children after diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD but lower for anti-ICA512 and ICA in adults. Our observations show in women the long latency of seropositivity before overt IDDM, the predominance of anti-GAD among these three serological markers, and the presence of these markers in NIDDM presumably representing a NIDDM phase of autoimmune insulitis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Whittingham
authors.forename: S L
authors.initials: SL
authors.lastname: Byron
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: P Z
authors.initials: PZ
authors.lastname: Zimmet
authors.forename: M A
authors.initials: MA
authors.lastname: Myers
authors.forename: G
authors.initials: G
authors.lastname: Vidgren
authors.forename: M J
authors.initials: MJ
authors.lastname: Rowley
authors.forename: S J
authors.initials: SJ
authors.lastname: Feeney
authors.forename: P
authors.initials: P
authors.lastname: Koskela
authors.forename: E
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D011247:Pregnancy; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D011897:Random Allocation; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D008565:Membrane Proteins; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase