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Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis.
Williams, MacKenzie D; Bacher, Rhonda; Perry, Daniel J; Grace, C Ramsey; McGrail, Kieran M; Posgai, Amanda L; Muir, Andrew; Chamala, Srikar; Haller, Michael J; Schatz, Desmond A; Brusko, Todd M; Atkinson, Mark A; Wasserfall, Clive H.
Afiliación
  • Williams MD; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Bacher R; Department of Biostatistics, College of Public Health and Health Professions, and College of Medicine, University of Florida, Gainesville, FL.
  • Perry DJ; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Grace CR; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • McGrail KM; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Posgai AL; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Muir A; Department of Pediatrics, Emory University, Atlanta, GA.
  • Chamala S; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Haller MJ; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Schatz DA; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Brusko TM; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Atkinson MA; Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
  • Wasserfall CH; Department of Pathology, Immunology and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL.
Diabetes ; 70(4): 932-943, 2021 04.
Article en En | MEDLINE | ID: mdl-33419759
We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual ß-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (median duration 4.5 years [range 0-60]). Indeed, a combined model with incorporation of disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A, and GADA provided superior capacity to predict C-peptide detection (quasi-likelihood information criterion [QIC] = 334.6) compared with the capacity of disease duration, age at onset, and GRS as the sole parameters (QIC = 359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials where investigators are seeking to preserve or restore endogenous ß-cell function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Diabetes Mellitus Tipo 1 / Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores Tipo de estudio: Diagnostic_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Diabetes Mellitus Tipo 1 / Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores Tipo de estudio: Diagnostic_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos