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  • 1
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    Online Resource
    Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
    American Diabetes Association ; 2019
    In:  Diabetes Care Vol. 42, No. 2 ( 2019-02-01), p. 192-199
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 2 ( 2019-02-01), p. 192-199
    Abstract: There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A] , and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P & lt; 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-0288
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 2
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    The Effect of Ethnicity in the Rate of Beta-Cell Functional Loss in the First 3 Years After Type 1 Diabetes Diagnosis
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 12 ( 2020-12-01), p. e4393-e4406
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 12 ( 2020-12-01), p. e4393-e4406
    Abstract: We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis. Research Methods and Design We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14). Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa348
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 3
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    A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk
    American Diabetes Association ; 2018
    In:  Diabetes Care Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1887-1894
    Abstract: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS & gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-0087
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1490520-6
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  • 4
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    Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes
    American Diabetes Association ; 2018
    In:  Diabetes Care Vol. 41, No. 9 ( 2018-09-01), p. 1917-1925
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 9 ( 2018-09-01), p. 1917-1925
    Abstract: A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration & lt;100 days). RESEARCH DESIGN AND METHODS A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value & lt; 0.025. RESULTS The 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Future studies should be considered to determine whether low-dose ATG alone or in combination with other agents may prevent or delay the onset of the disease.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-0494
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1490520-6
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  • 5
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    Th2 priming induced by intranasal exposure to soluble protein antigens
    Elsevier BV ; 2002
    In:  Journal of Allergy and Clinical Immunology Vol. 109, No. 1 ( 2002-01), p. S263-S263
    Details
    In: Journal of Allergy and Clinical Immunology, Elsevier BV, Vol. 109, No. 1 ( 2002-01), p. S263-S263
    Type of Medium: Online Resource
    ISSN: 0091-6749
    URL: Article
    DOI: 10.1016/S0091-6749(02)81937-6
    RVK:
    XA 52000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
    detail.hit.zdb_id: 2006613-2
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  • 6
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    Online Resource
    Lipopolysaccharide-enhanced, Toll-like Receptor 4–dependent T Helper Cell Type 2 Responses to Inhaled Antigen
    Rockefeller University Press ; 2002
    In:  The Journal of Experimental Medicine Vol. 196, No. 12 ( 2002-12-16), p. 1645-1651
    Details
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 196, No. 12 ( 2002-12-16), p. 1645-1651
    Abstract: Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
    URL: Article
    DOI: 10.1084/jem.20021340
    RVK:
    XA 10000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2002
    detail.hit.zdb_id: 1477240-1
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  • 7
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    MyD88-dependent induction of allergic Th2 responses to intranasal antigen
    American Society for Clinical Investigation ; 2005
    In:  Journal of Clinical Investigation Vol. 115, No. 2 ( 2005-2-1), p. 459-467
    Details
    In: Journal of Clinical Investigation, American Society for Clinical Investigation, Vol. 115, No. 2 ( 2005-2-1), p. 459-467
    Type of Medium: Online Resource
    ISSN: 0021-9738
    URL: Article
    DOI: 10.1172/JCI200522462
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2005
    detail.hit.zdb_id: 2018375-6
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  • 8
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    Potentials of hydroactive lightweight façades for urban climate resilience
    Wiley ; 2022
    In:  Civil Engineering Design Vol. 4, No. 1-3 ( 2022-06), p. 14-24
    Details
    In: Civil Engineering Design, Wiley, Vol. 4, No. 1-3 ( 2022-06), p. 14-24
    Abstract: Extreme heat and heavy rainfall events with severe inundations have a significant impact on urban architecture, resulting in considerable personal injuries and material damage. Nowadays, the proportion of façade surface in urban areas with tall buildings is substantially larger than the proportion of horizontal roof or ground surface areas. A high leverage effect on climate resilience and sustainability of buildings and cities can therefore be attributed to the building envelopes. Whereas the majority of existing façades are designed to provide only minor qualities at a district or urban level, research at the Institute for Lightweight Structures and Conceptual Design (ILEK) at the University of Stuttgart focuses on development of a new type of hydroactive lightweight façades incorporating climate change mitigation and adaptation strategies. A textile‐ and film‐based façade element called HydroSKIN is capable of providing a retention surface on the envelope of the building. With a minimal amount of embedded mass, energy, and CO 2 emissions, the façade add‐on element is suitable for both new and existing buildings. HydroSKIN combines rainwater harvesting (RWH) and run‐off water reduction by retaining the precipitation water that strikes the façade with a time‐delayed evaporative cooling (EC) of the building and its environment.
    Type of Medium: Online Resource
    ISSN: 2625-073X , 2625-073X
    URL: Issue
    URL: Article
    DOI: 10.1002/cend.v4.1-3
    DOI: 10.1002/cend.202200003
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2933000-2
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  • 9
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    Ökobilanzierung adaptiver Hüllen und Strukturen
    Wiley ; 2023
    In:  Bauphysik Vol. 45, No. 2 ( 2023-04), p. 107-121
    Details
    In: Bauphysik, Wiley, Vol. 45, No. 2 ( 2023-04), p. 107-121
    Abstract: Life cycle assessment of adaptive skins and structures The assessment of environmental impacts is crucial in the development of sustainable and environmentally friendly technologies and concepts. The development of adaptive buildings is no exception and also places far‐reaching demands on all disciplines involved. The full integration of life cycle assessment into the planning and design process makes it possible to use environmental impacts as optimization parameters in the complex, dynamic calculation tools. The results of SFB 1244 to date confirm that adaptive load‐bearing structures and façades have great potential for saving resources and environmental impacts. The holistic approach, both in terms of the life cycle and the interdisciplinary dependencies, ensures that the relevant effects and influences are taken into account in the assessment. However, this confronts the life cycle assessment method with new challenges in dealing with a large number of variants and the extensive interactions between design and influences on parameters in the use phase, such as energy consumption or service life.
    Type of Medium: Online Resource
    ISSN: 0171-5445 , 1437-0980
    URL: Issue
    URL: Article
    DOI: 10.1002/bapi.v45.2
    DOI: 10.1002/bapi.202300102
    RVK:
    ZG 1100
    RVK:
    ZI 0001
    Language: German
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2151235-8
    detail.hit.zdb_id: 244802-6
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  • 10
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    IL-4-Dependent Th2 Collateral Priming to Inhaled Antigens Independent of Toll-Like Receptor 4 and Myeloid Differentiation Factor 88
    The American Association of Immunologists ; 2004
    In:  The Journal of Immunology Vol. 172, No. 7 ( 2004-04-01), p. 4527-4534
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 172, No. 7 ( 2004-04-01), p. 4527-4534
    Abstract: Allergic asthma is an inflammatory lung disease thought to be initiated and directed by type 2 helper T cells responding to environmental Ags. The mechanisms by which allergens induce Th2-adaptive immune responses are not well understood, although it is now clear that innate immune signals are required to promote DC activation and Th2 sensitization to inhaled proteins. However, the effect of ongoing Th2 inflammation, as seen in chronic asthma, on naive lymphocyte activation has not been explored. It has been noted that patients with atopic disorders demonstrate an increased risk of developing sensitivities to new allergens. This suggests that signals from an adaptive immune response may facilitate sensitization to new Ags. We used a Th2-adoptive transfer murine model of asthma to identify a novel mechanism, termed “collateral priming,” in which naive CD4+ T cells are activated by adaptive rather than innate immune signals. Th2 priming to newly encountered Ags was dependent on the production of IL-4 by the transferred Th2 population but was independent of Toll-like receptor 4 signaling and the myeloid differentiation factor 88 Toll-like receptor signaling pathway. These results identify a novel mechanism of T cell priming in which an Ag-specific adaptive immune response initiates distinct Ag-specific T cell responses in the absence of classical innate immune system triggering signals.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.172.7.4527
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2004
    detail.hit.zdb_id: 1475085-5
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