title: GADA and anti-ZnT8 complicate the outcome of phenotypic type 2 diabetes of adults.
abstract: BACKGROUND
  A proportion of phenotypic type 2 diabetes (T2D) patients produce pancreatic autoantibodies and a majority of T2D patients develop serious life-disabling complications over time despite the implementation of adequate clinical interventions. This study determined whether the presence of pancreatic autoantibodies (GADA, IA-2A, anti-ZnT8, or ICA) was associated with serious complications or concomitant diseases of adult patients diagnosed with T2D (N = 305).
  
  
  RESULTS
  In the study population, 22.3% (N = 68) of subjects were positive for at least 1 of the 4 of the markers associated with autoimmune diabetes (presence of pancreatic autoantibody - pAb), followed by GADA (14.1%, N = 43), ICA (8.9%, N = 27), anti-ZnT8 (5.6%, N = 17) and IA-2A (2.0%, N = 6). Logistic regression analysis adjusted for patient's age, gender and duration of T2D revealed that (i) pAb was associated with higher prevalence of adiposity (odds ratio of adjusted regression model (adOR) 2.51, P = 0.032); (ii) pAb, GADA and anti-ZnT8 were associated with autoimmune thyroid disease (adORs 3.07, P = 0.012; 6.29, P < 0.001 and 3.52, P = 0.052, respectively); (iii) pAb and GADA, in particular, were risk factors for neurological complications (adORs 2.10, P = 0.036; 2.76, P = 0.009, respectively) and polyneuropathy in particular (adORs 2.60, P = 0.012; 3.10, P = 0.007, respectively); and (iv) anti-ZnT8 was a risk factor for developing nephropathy (adOR 4.61, P = 0.022). In addition, adiposity was associated with 5.3-year earlier onset of disease (adjusted linear regression model, P = 0.006).
  
  
  CONCLUSIONS
  These results suggest that GADA and anti-ZnT8 are associated with progression of serious T2D complications, including polyneuropathy and nephropathy. In addition, adiposity represents a significant risk for autoimmunity development in T2D patients.
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Competence Centre on Health Technologies, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.
authors.forename: Kadri
authors.initials: K
authors.lastname: Haller-Kikkatalo
authors.forename: Katrin
authors.initials: K
authors.lastname: Pruul
authors.forename: Kalle
authors.initials: K
authors.lastname: Kisand
authors.forename: Virge
authors.initials: V
authors.lastname: Nemvalts
authors.forename: Koit
authors.initials: K
authors.lastname: Reimand
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
mesh_terms: D050154:Adiposity / Q000276:immunology; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D027682:Cation Transport Proteins / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D027682:Cation Transport Proteins; D007074:Immunoglobulin G; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D005968:Glutamate Decarboxylase
keywords: Anti-ZnT8; GADA; nephropathy; phenotypic type 2 diabetes of adults; polyneuropathy