Autoimmune Type 1 diabetes is characterized by the loss of self-tolerance to
insulin-producing beta cells in the pancreas. Self-antigen specific tolerance
strategies that mobilize the body´s own safeguards (regulatory T cells that
suppress self-reactive T cells) are required for safe and specific prevention of
Type 1 diabetes.
Fopx3+ regulatory T (Treg) cells function as an
essential cellular constituent of the immune system in order to maintain
immunological self-tolerance. T cell receptor ligation is required for the
differentiation of Foxp3+ Treg cells, a process, which can be induced intra- or
extrathymically.
We established that extrathymic induction of Foxp3+Treg
cells can be best achieved in vivo by the delivery of strong-agonistic T cell
receptor ligands under subimmunogenic conditions, avoiding strong activation of
T cells and antigen-presenting cells. In contrast, weak agonistic ligands fail
to induce stable Foxp3+ Treg cells irrespective of the applied dose.
In
mouse models of Type 1 diabetes we found that the weak-agonistic properties of
the critical autoantigen insulin (insulin beta chain peptides) result in poor
differentiation of naïve insulin-specific T cells into Foxp3+ Treg cells. A
strong-agonistic variant of the insulin beta chain peptide (insulin mimetope)
was suited to efficiently generate insulin-specific Foxp3+ Treg cells in
vivo.
Based on findings in the mouse system, here we are interested in
investigating the role of self-antigen presentation and recognition for the
induction of human Foxp3+ Treg cells. In addition, we are studying critical
factors involved in the regulation of T cell activation in order to characterize
their impact on the generation and function of Foxp3+Treg cells in
vivo.
The studies aim at improving the understanding of Treg
differentiation at the cellular and molecular level with the goal to facilitate
the future development of Treg induction strategies in order to combat unwanted
immunity such as Type 1 diabetes.
Monday, 28 October 2013
Gestational diabetes mellitus
Gestational diabetes mellitus type 2 diabetes Pathogenesis and Prevention
Gestational diabetes, defined as glucose intolerance did begins or is first
Recognized during pregnancy, has a prevalence of 2-6% with at Increasing trend
across most racial / ethnic groups Studied. Women with gestational diabetes are
at Increased risk to develop type 2 diabetes postpartum. Results from our
prospective German Gestational-diabetes-study Showed did women who required
insulin treatment during pregnancy had a postpartum diabetes-risk of 61% by 3
years postpartum. One focus of our research group is to identify risk factors
and mechanisms did are related to postpartum diabetes-risk in a cohort of more
than 800 mothers with gestational diabetes (German Prospective
Gestational-diabetes-study and POGO study).
Further More we are Conducting two studies aiming to preventable postpartum onset of diabetes in women with gestational diabetes. PENGUIN mothers in the study are administered a DPP4 inhibitor postpartum and are advised to change lifestyle, the Muki-study investigates Whether a change in activity behavior may preventable postpartum diabetes in mothers with gestational diabetes.
Several studies did Indicated in utero exposure to gestational diabetes is a strong risk factor for overweight and type 2 diabtes in the offspring during childhood and adolescence. THEREFORE A second objective is to identify mechanisms underlying the overweight Increased risk in offspring of mothers with gestational diabetes. By Following Following more than 800 offspring of mothers with gestational diabetes (Prospective German Gestational-diabetes-study and POGO study), in depth analysis of genetic and environmental determinants of overweight and type 2 diabetes and mechanistic studies, in Particular microbiome analysis, are performed.
Type 1 diabetes prevention
Type 1 diabetes prevention
Diabetes prevention has stopped aims to prevent the development of islet autoimmunity in children with a familial or genetic risk (primary prevention) or the extent of beta cell destruction in antibody-positive children and adults (secondary prevention). Immune interventions have the goal to reduce the autoreactive immune response and to preserve the remaining beta cell mass (tertiary prevention after onset of type 1 diabetes).
The efficacy of therapeutic strategies for diabetes prevention is not yet definitively proven. Previously completed studies show promising results, but since dose-finding, age-dependent effect and safety of these therapies have not been researched, these therapies are not routinely available. So diabetes prevention takes place in controlled studies in which patients can participate with newly manifest diabetes or people with increased risk of diabetes.
Diabetes prevention has stopped aims to prevent the development of islet autoimmunity in children with a familial or genetic risk (primary prevention) or the extent of beta cell destruction in antibody-positive children and adults (secondary prevention). Immune interventions have the goal to reduce the autoreactive immune response and to preserve the remaining beta cell mass (tertiary prevention after onset of type 1 diabetes).
The efficacy of therapeutic strategies for diabetes prevention is not yet definitively proven. Previously completed studies show promising results, but since dose-finding, age-dependent effect and safety of these therapies have not been researched, these therapies are not routinely available. So diabetes prevention takes place in controlled studies in which patients can participate with newly manifest diabetes or people with increased risk of diabetes.
Diabetes risk screening
Diabetes risk screening
Type 1 diabetes is an autoimmune disease, during which the insulin-producing beta cells of the pancreas are destroyed by the body's own immune cells. Most of this process is gradual, so that the person concerned for a long time unaware of their condition. Only the complete absence of insulin production leads to serious symptoms, often with complications
Type 1 diabetes is an autoimmune disease, during which the insulin-producing beta cells of the pancreas are destroyed by the body's own immune cells. Most of this process is gradual, so that the person concerned for a long time unaware of their condition. Only the complete absence of insulin production leads to serious symptoms, often with complications
go hand in hand. First-degree relatives of people with type 1 diabetes have to suffer an average of 5 percent risk itself. In the general population the risk is, however, only 0.3 percent.
To actively do "type 1 diabetes" something against the disease before the diagnosis, research, the Institute for Diabetes Research, Helmholtz Center Munich, headed by Univ.-Prof. Dr. Anette-Gabriele Ziegler, on new ways to better predictability of type 1 diabetes. To this end, the scientists use a four-car antibody test, which helps to estimate the probability of disease more accurately.
The Diabetes Research Institute provides first-degree relatives (children, siblings or parents) of type 1 diabetes from 1 to 30 Age of free to leave determine their individual risk of diabetes.
Each participant will receive a letter about the findings islet autoantibodies status and individual counseling. Depending on the state, it is advisable to check again to make the findings between 6 months and 5 years. If two or more antibodies can be detected, is for those affected if appropriate, the opportunity to participate in a prevention study by the Institute to actively prevent the possible onset of type 1 diabetes.
Lower risk of diabetes with good vitamin D supply
Scientists at the Helmholtz Zentrum München have discovered together with
partners from the German Diabetes Center and the University of Ulm Dusseldorf
that people with a good supply of vitamin D have a lower risk of type 2 diabetes
mellitus. The study was based on the evaluation of old data and determined study
provide important clues to the mechanism of formation and prevention of disease.
The human body can produce sufficient amount of vitamin D itself only when the people stay long enough in the open. The UVB radiation present in daylight splits the precursor of vitamin D, 7-dehydrocholesterol in the skin, it creates previtamin D3. The more vitamin D synthesis is then carried out in the liver and kidney. Lack of appropriate sunlight - such as in the winter due to the geographical latitude - danger of a shortage. The problem is exacerbated by the modern lifestyle, which often does not require longer stays outdoors more.
Researchers at the Helmholtz Zentrum München have studied together with partners participants in the MONICA / KORA study for their vitamin D status. As part of the MONICA / KORA studies are at the Helmholtz Zentrum München since 1984, data collected from the Augsburg population. MONICA stands for Monitoring of Trends and Determinants in Cardiovascular Diseases and was under KORA - continued Health Research in the Augsburg Region Cooperative.
The researchers found that people with a good vitamin D supply have a lower risk of developing type 2 diabetes mellitus disease. For people with insufficient levels of vitamin D in the blood, by contrast, there is an increased risk of diabetes. This effect could be in part to the anti-reducing effect of vitamin D-recirculate. The result of the performed among others in collaboration with Christian Herder, German Diabetes Center Dusseldorf and Wolfgang Koenig of the University of Ulm Helmholtz Zentrum München study could have direct implications for the prevention of endemic disease. Researchers at the Helmholtz Zentrum München have access to the data from the MONICA / KORA Augsburg study the unique opportunity to explore the relationships between lifestyle factors and type 2 diabetes in more detail.
The vitamin D supply is relatively easy to improve by a sufficient outdoor exposure (in Germany from spring to autumn), and by the absorption of vitamin D-containing supplements. Therefore, it is particularly relevant to clarify in future studies whether the association between vitamin D status and incidence of type 2 diabetes, the Helmholtz researchers have observed in the population-based MONICA / KORA study, is causal. If subsequent studies confirm this, could reduce the risk of diabetes targeted improving the vitamin D status of the population.
The human body can produce sufficient amount of vitamin D itself only when the people stay long enough in the open. The UVB radiation present in daylight splits the precursor of vitamin D, 7-dehydrocholesterol in the skin, it creates previtamin D3. The more vitamin D synthesis is then carried out in the liver and kidney. Lack of appropriate sunlight - such as in the winter due to the geographical latitude - danger of a shortage. The problem is exacerbated by the modern lifestyle, which often does not require longer stays outdoors more.
Researchers at the Helmholtz Zentrum München have studied together with partners participants in the MONICA / KORA study for their vitamin D status. As part of the MONICA / KORA studies are at the Helmholtz Zentrum München since 1984, data collected from the Augsburg population. MONICA stands for Monitoring of Trends and Determinants in Cardiovascular Diseases and was under KORA - continued Health Research in the Augsburg Region Cooperative.
The researchers found that people with a good vitamin D supply have a lower risk of developing type 2 diabetes mellitus disease. For people with insufficient levels of vitamin D in the blood, by contrast, there is an increased risk of diabetes. This effect could be in part to the anti-reducing effect of vitamin D-recirculate. The result of the performed among others in collaboration with Christian Herder, German Diabetes Center Dusseldorf and Wolfgang Koenig of the University of Ulm Helmholtz Zentrum München study could have direct implications for the prevention of endemic disease. Researchers at the Helmholtz Zentrum München have access to the data from the MONICA / KORA Augsburg study the unique opportunity to explore the relationships between lifestyle factors and type 2 diabetes in more detail.
The vitamin D supply is relatively easy to improve by a sufficient outdoor exposure (in Germany from spring to autumn), and by the absorption of vitamin D-containing supplements. Therefore, it is particularly relevant to clarify in future studies whether the association between vitamin D status and incidence of type 2 diabetes, the Helmholtz researchers have observed in the population-based MONICA / KORA study, is causal. If subsequent studies confirm this, could reduce the risk of diabetes targeted improving the vitamin D status of the population.
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