Patients with LADA – a form of autoimmune type 1 diabetes in adulthood - can be distinguished from patients with non-autoimmune type 2 diabetes by means of the antibody reaction affinity to the enzyme glutamic acid decarboxylase (GAD). Scientists from the Helmholtz Zentrum München have reported in the journal ‘Diabetes Care’ that high-affinity GAD antibodies are found in patients who produce only a little of their own insulin and who will require insulin therapy after only a relatively short time.

LADA (latent autoimmune diabetes in adults) is a form of type 1 diabetes in adulthood. Like the childhood form, the insulin-producing beta cells of the pancreas are destroyed by the body’s own immune system. The progression of the illness is relatively slowly, however, with clinical manifestations not appearing until after the age of 30 and the patients not yet requiring insulin therapy to control blood sugar levels at the beginning of the disease. It is therefore often difficult to differentiate between LADA and type 2 diabetes.

Scientists from the Institute of Diabetes Research at the Helmholtz Zentrum München, partners in the Deutsches Zentrum für Diabetesforschung (DZD - German Center for Diabetes Research), have now examined the extent to which the GAD antibody affinity, as a measure of the maturity of the immune response, improves the classification of diabetes in adulthood. They also wanted to determine if vaccination with GAD influences the antibody affinity.

High antibody affinity identifies type 1 diabetes

Together with national and international colleagues, the team headed by PD Dr. Peter Achenbach, Stephanie Krause and Prof. Dr. Anette-Gabriele Ziegler examined the GAD antibody affinity in 46 LADA patients who participated in a GAD vaccination study. The study participants were injected under the skin with different doses of GAD or a placebo preparation in order to induce immune system tolerance to the beta cells. Interestingly, the GAD antibody affinity differed considerably even before the treatment, so that it was possible to distinguish between patients with high and low affinity. The patients with high GAD antibody affinity displayed low insulin production, in keeping with advanced autoimmune destruction of the beta cells. This patient group frequently needed insulin therapy after just a relatively short time. Patients with low affinity, on the other hand, displayed a considerably higher level of insulin production, which remained constant over a time frame of 30 months. The GAD antibody affinity was not influenced by the vaccination with GAD.

“Our findings show that the GAD antibody affinity is a valuable new diagnostic marker in LADA patients. As with childhood type 1 diabetes, we can forecast the progression of the disease and adapt the therapeutic measures accordingly,” lead investigator Achenbach explains. “The antibody affinity should now also be taken into consideration in clinical studies involving LADA patients.”

In addition to the Helmholtz Zentrum München, the Center for Regenerative Therapies at TU Dresden, another partner of the DZD - German Center for Diabetes Research, and the Skane University Hospital, Sweden, also participated in the work.

You can read more about type 1 diabetes research at the Helmholtz Zentrum München

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Further information
You can find additional information about diabetes studies at the Helmholtz Zentrum München/ Technische Universität München at: http://www.diabetes-studien.de

Original publication:
Krause, S. et al. (2014): GAD Autoantibody Affinity in Adult Patients with Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial, Diabetes Care, doi: 10.2337/dc13-1719

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The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medicine, i.e. a customized approach to the diagnosis, treatment and prevention of widespread diseases such as diabetes mellitus and lung disease. To that end, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich. It has about 2,200 staff members and is a member of the Helmholtz Association, Germany’s largest scientific organization, a community of 18 scientific-technical and medical-biological research centers with some 34,000 staff members. The Helmholtz Zentrum München is a partner in the German Center for Diabetes Research.

The German Center for Diabetes Research e.V. brings together experts in the field of diabetes research and combines basic research, epidemiology and clinical applications. The members of the association are the German Diabetes Center (DDZ) in Düsseldorf, the German Institute of Human Nutrition (DifE) in Potsdam-Rehbrücke, the Helmholtz Zentrum München – the German Research Center for Environmental Health, the Paul Langerhans Institutes of the Carl Gustav Carus University Hospital in Dresden and the Eberhard Karl University of Tübingen as well as the Gottfried Wilhelm Leibniz Research Association and the Helmholtz Association of German Research Centers. The aim of the DZD is to find answers to unsolved questions in diabetes research by adopting a novel, integrative approach and to make a significant contribution towards improving the prevention, diagnosis and treatment of diabetes mellitus.

The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes and the long-term effects of gestational diabetes. A major project is the development of an insulin vaccination against type 1 diabetes. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world’s first prospective birth cohort study, identified risk genes and antibody profiles. These permit predictions to be made about the pathogenesis and onset of type 1 diabetes and will lead to changes in the classification and the time of diagnosis. The IDF is part of the Helmholtz Diabetes Center (HDC).

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Helmholtz Zentrum München -
Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
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Germany
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