Institute of Diabetes Research

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Institute for Diabetes Research, Helmholtz Zentrum München
Forschergruppe Diabetes der Technischen Universität München (TUM)

Director: Univ.-Prof. Dr. med. Anette-Gabriele Ziegler
Deputy Director: Dr. med. Peter Achenbach

 

The main research area of the Institute of Diabetes Research is the pathogenesis and prevention of diabetes. The institute focuses on type 1 as well as on gestational diabetes with the aim to identify mechanisms underlying disease initiation and progression, to explore gene-environment interactions leading to diabetes development, to define markers for early diagnosis of type 1 and type 2 diabetes and to develop intervention strategies. In addition, pre-clinical models are used to examine mechanisms leading to the initiation of islet autoimmunity and to conduct prevention studies.

Pathogenesis – Type 1 Diabetes

The objective is to determine the natural history of autoimmune diabetes and identify the genetic and environmentaldeterminants of autoimmunity.

  • Prospective intensive follow-up from birth of up to 4000 at risk children (family history and/or genetic susceptibility).
  • Bavarian diabetes incidence cohort of children and adolescents aged 0-20 years
  • Puberty cohort: Prospective follow-up of 1500 at risk children from age 8 to 18 years
  • Mechanistic studies of humoral (antibodies) and cell-mediated (autoreactive T cells) immunity.
  • Models of type 1 diabetes prediction (genetic and immune markers) to identify subjects that can be targeted for intervention.
  • In depth analysis of childhood nutrition and it’s contribution to disease
  • Animal models to examine environmental determinants of autoimmune diabetes

National and international studies:

  • Type 1 diabetes genetic consortium (NIH)
  • TEDDY The Environmental Determinants of Diabetes in the Young Study (NIH)
  • TrialNet (NIH)
  • BABYDIAB (JDRF)
  • TEENDIAB (BMBF)
  • DiMelli (BMBF)

Prevention – Type 1 Diabetes

The objective is to perform intervention aimed at 1. preventing the initiation of autoimmunity, 2. preventing progression to disease, and 3. restoring beta cell function after disease onset.

Target populations

  • Genetically at risk newborns and children up to 4 years
  • Autoimmune prediabetic relatives of patients with T1DM
  • New or recent onset patients with type 1 diabetes (children and adults)

Interventions

  • Nutritional modification
  • Autoantigen based therapies (mucosal insulin, insulin altered peptide ligand, HSP peptide)
  • Immune modulation (1,25 Vitamin D3)
  • Antibody-based immunotherapy (anti-CD3, ATG)
  • Immunosuppression (MMF/Daclizumab)

Intervention is performed as phase II/III studies that are investigator based national studies, multicenter consortia (TrialNet - NIH), or pharmaceutical sponsored trials. The prevention programme includes mechanistic studies of immune function post intervention and preclinical studies in the NOD mouse model of autoimmune diabetes.

Pathogenesis and Prevention – Type 2 Diabetes/Gestational Diabetes mellitus

The objective is to identify risk factors and mechanisms leading to the development of type 2 diabetes postpartum in women with Gestational diabetes and to perform intervention studies aiming to prevent the development of type 2 diabetes postpartum. A second objective is to identify mechanisms underlying the increased overweight risk in offspring of mothers with GDM.

  • Prospective follow-up of up to 800 women with GDM and their offspring
  • In depth analysis of genetic and environmental determinants of overweight and type 2 diabetes
  • Mechanistic studies, in particular microbiome analysis
  • Intervention with an DPP4 inhibitor and lifestyle changes (diet and activity) to prevent type 2 diabetes postpartum in mothers with GDM