Nanette C Schloot1, Minh N Pham2,3, Mohammed I Hawa4, Paolo Pozzilli5, Werner A Scherbaum6, Matthias Schott7, Hubert Kolb8, Steven Hunter9, Guntram Schernthaner10, Charles Thivolet11, Jochen Seissler12, Richard David Leslie4. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany nanette.schloot@web.de. 2. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany. 3. Novo Nordisk Research Center, Seattle, WA. 4. Blizard Institute, Queen Mary University of London, London, U.K. 5. Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy. 6. University of Düsseldorf, Medical Faculty, Düsseldorf, Germany. 7. University of Düsseldorf, Medical Faculty, Division for Specific Endocrinology, Düsseldorf, Germany. 8. West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany. 9. Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Ireland. 10. Department of Medicine, Rudolfstiftung Hospital, Vienna, Austria. 11. Department of Endocrinology and Diabetes, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Benite, France; Université Claude-Bernard Lyon, Lyon, France. 12. Medizinische Klinik und Poliklinik IV, Diabetes Center, Ludwig-Maximillians-University, Munich, Germany.
Abstract
OBJECTIVE: We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). RESULTS: Type 1 diabetes patients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetes patients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). CONCLUSIONS: Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.
OBJECTIVE: We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). RESULTS:Type 1 diabetespatients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetespatients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). CONCLUSIONS:Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.
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