Time dynamics of autoantibodies are coupled to phenotypes  and add to the heterogeneity of autoimmune diabetes  in adults: the HUNT study, Norway.
OBJECTIVE
The aetiology of latent autoimmune diabetes in adults (LADA), assessed by autoimmune markers, is insufficiently clarified. We cross-sectionally investigated the prevalence and prospectively the prediabetic and postdiabetic presence of antibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 and zinc transporter 8 in LADA and in type 1 diabetes.


METHODS
We included 208 'classic' type 1, 161 LADA and 302 type 2 diabetic cases from the second (HUNT2: 1995–1997) and third (HUNT3: 2006–2008) Nord-Trøndelag health surveys. Prospective data were available for 59 type 1, 44 LADA and 302 type 2 diabetic cases followed from HUNT2 to HUNT3. From HUNT3, 24 type 1 diabetic and 31 LADA incident cases were available.


RESULTS
Cross-sectionally, 90% of LADA cases were positive for only one antibody (10% multiple-antibodypositive). Prospectively, 59% of GADA-positive LADA patients in HUNT2 were no longer positive in HUNT3. LADA patients who became negative possessed less frequently risk HLA haplotypes and were phenotypically more akin to those with type 2 diabetes than to those who stayed positive. Still, those losing positivity differed from those with type 2 diabetes by lower C-peptide levels (p = 0.009). Of incident LADA cases in HUNT3, 64% were already antibody-positive in HUNT2, i.e. before diabetes diagnosis. These incident LADA cases were phenotypically more akin to type 1 diabetes than were those who did not display positivity in HUNT2.


CONCLUSIONS
The pattern of antibodies, the postdiabetic loss or persistence as well as the prediabetic absence or presence of antibodies influence LADA phenotypes. Time-dependent presence or absence of antibodies adds new modalities to the heterogeneity of LADA.
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, NTNU, HUNT Research Centre, Forskningsveien 2, 7600 Levanger, Norway. elin.pettersen@ntnu.no
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D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D002096:C-Peptide / Q000097:blood / Q000276:immunology; D027682:Cation Transport Proteins / Q000276:immunology; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology; D015995:Prevalence; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012306:Risk; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D002096:C-Peptide; D027682:Cation Transport Proteins; D006680:HLA Antigens; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase