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  1. Article ; Online: Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant.

    van Tienhoven, René / Vu, Anh Nguyet / Kaddis, John S / Roep, Bart O

    PloS one

    2023  Volume 18, Issue 1, Page(s) e0280872

    Abstract: Type 1 diabetes patients carrying a 'protective' insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant ... ...

    Abstract Type 1 diabetes patients carrying a 'protective' insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term diabetic complications. Insulin gene polymorphisms were evaluated in 1,363 type 1 diabetes patients participating in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study that compared intensive versus conventional insulin therapy in relation with development of PDR and DKD with a follow-up of over two decades. PDR and DKD were absent in type 1 diabetes patients carrying the protective INS variant and receiving intensive insulin therapy (the current standard of clinical care) 1-5 years from their diagnosis (n = 67; mean post-diagnosis follow up of 20.4 ± 1.6 years), versus 11 of 258 patients (4.3%) lacking this variant (20.4 ± 1.8 years follow up). In the secondary intervention group of the intensive therapy arm (1-15 years of disease), PDR was significantly less frequent in carriers of the protective INS variant than those without it (4 of 83 [4.8%] vs. 31 of 260 [11.9%]; p = 0.032; 26.1 ± 3.9 and 26.3 ± 4.1 years follow-up, respectively), whereas DKD frequencies were no different between those with or without this variant (5 of 83 [6.0%] vs. 11 of 260 [4.2%]). Carrying a copy of this protective INS variant further reduces the risk of diabetic complications achieved by intensive insulin therapy and marks a disease endotype with superior glycemic control, increased and extended beta cell function, and prevention of DKD and PDR.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/genetics ; Insulin/therapeutic use ; Blood Glucose/metabolism ; Glycated Hemoglobin ; Diabetic Retinopathy/diagnosis ; Insulin, Regular, Human/therapeutic use
    Chemical Substances Insulin ; Blood Glucose ; Glycated Hemoglobin ; Insulin, Regular, Human
    Language English
    Publishing date 2023-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0280872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Author Correction: Generation of human islet cell type-specific identity genesets.

    van Gurp, Léon / Fodoulian, Leon / Oropeza, Daniel / Furuyama, Kenichiro / Bru-Tari, Eva / Vu, Anh Nguyet / Kaddis, John S / Rodríguez, Iván / Thorel, Fabrizio / Herrera, Pedro L

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2574

    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46525-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Improving the Prediction of Type 1 Diabetes Across Ancestries.

    Kaddis, John S / Perry, Daniel J / Vu, Anh Nguyet / Rich, Stephen S / Atkinson, Mark A / Schatz, Desmond A / Roep, Bart O / Brusko, Todd M

    Diabetes care

    2022  Volume 45, Issue 3, Page(s) e48–e50

    MeSH term(s) Diabetes Mellitus, Type 1/diagnosis ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans
    Language English
    Publishing date 2022-01-18
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
    DOI 10.2337/dc21-1254
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Methylglyoxal Adducts Are Prognostic Biomarkers for Diabetic Kidney Disease in Patients With Type 1 Diabetes.

    Lai, Seigmund Wai Tsuen / Hernandez-Castillo, Carlos / Gonzalez, Edwin De Jesus Lopez / Zoukari, Tala / Talley, Min / Paquin, Nadia / Chen, Zhuo / Roep, Bart O / Kaddis, John S / Natarajan, Rama / Termini, John / Shuck, Sarah C

    Diabetes

    2023  Volume 73, Issue 4, Page(s) 611–617

    MeSH term(s) Humans ; Diabetes Mellitus, Type 1/complications ; Diabetic Nephropathies/metabolism ; Pyruvaldehyde ; Follow-Up Studies ; Prognosis ; Glycated Hemoglobin ; Biomarkers/metabolism ; Glomerular Filtration Rate
    Chemical Substances Pyruvaldehyde (722KLD7415) ; Glycated Hemoglobin ; Biomarkers
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db23-0277
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Tolerogenic dendritic cells pulsed with islet antigen induce long-term reduction in T-cell autoreactivity in type 1 diabetes patients.

    Nikolic, Tatjana / Suwandi, Jessica S / Wesselius, Joris / Laban, Sandra / Joosten, Antoinette M / Sonneveld, Petra / Mul, Dick / Aanstoot, Henk-Jan / Kaddis, John S / Zwaginga, Jaap Jan / Roep, Bart O

    Frontiers in immunology

    2022  Volume 13, Page(s) 1054968

    Abstract: Introduction: Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production !## ...

    Abstract Introduction: Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production
    Methods: A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry.
    Results: The tolDC vaccine induced a profound and durable decline in pre-existing autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS
    Discussion: Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D.
    Language English
    Publishing date 2022-11-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1054968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A run on the biobank: what have we learned about type 1 diabetes from the nPOD tissue repository?

    Kaddis, John S / Pugliese, Alberto / Atkinson, Mark A

    Current opinion in endocrinology, diabetes, and obesity

    2015  Volume 22, Issue 4, Page(s) 290–295

    Abstract: Purpose of review: Since the inaugural year of its biobank in 2007, the Network for Pancreatic Organ Donors with Diabetes program has provided 70 370 human samples to 127 investigators worldwide for projects focused on the pathogenesis of type 1 ... ...

    Abstract Purpose of review: Since the inaugural year of its biobank in 2007, the Network for Pancreatic Organ Donors with Diabetes program has provided 70 370 human samples to 127 investigators worldwide for projects focused on the pathogenesis of type 1 diabetes (T1D). The purpose of this review was to highlight major advances in our understanding of T1D using works that contain original data from experiments utilizing biospecimens provided by the Network for Pancreatic Organ Donors with Diabetes program. A total of 15 studies, published between 1 June 2013 and 31 December 2014, were selected using various search and filter strategies.
    Recent findings: The type and frequency of B and/or T-cell immune markers in both the endocrine and exocrine compartments vary in T1D. Enterovirus signals have been identified as having new proteins in the extracellular matrix around infiltrated islets. Novel genes within human islet cell types have been shown to play a role in immunity, infiltration, inflammation, disease progression, cell mass and function. Various cytokines and a complement degradation product have also been detected in the blood or surrounding pancreatic ducts/vasculature.
    Summary: These findings, from T1D donors across the disease spectrum, emphasize the notion that pathogenic heterogeneity is a hallmark of the disorder.
    MeSH term(s) Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Humans ; Pancreas/immunology ; Pancreas/pathology ; Tissue Banks
    Language English
    Publishing date 2015-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2272017-0
    ISSN 1752-2978 ; 1752-296X
    ISSN (online) 1752-2978
    ISSN 1752-296X
    DOI 10.1097/MED.0000000000000171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Generation of human islet cell type-specific identity genesets.

    van Gurp, Léon / Fodoulian, Leon / Oropeza, Daniel / Furuyama, Kenichiro / Bru-Tari, Eva / Vu, Anh Nguyet / Kaddis, John S / Rodríguez, Iván / Thorel, Fabrizio / Herrera, Pedro L

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2020

    Abstract: Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we ... ...

    Abstract Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits.
    MeSH term(s) Cell Differentiation/genetics ; Humans ; Insulin/genetics ; Insulin-Secreting Cells ; Islets of Langerhans ; Pluripotent Stem Cells
    Chemical Substances Insulin
    Language English
    Publishing date 2022-04-19
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29588-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: From type 1 diabetes biology to therapy: The Human Islet Research Network.

    Kaddis, John S / Rouse, Layla / Parent, Audrey V / Saunders, Diane C / Shalev, Anath / Stabler, Cherie L / Stoffers, Doris A / Wagner, Bridget K / Niland, Joyce C

    Molecular metabolism

    2021  Volume 54, Page(s) 101283

    MeSH term(s) Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/therapy ; Humans ; Insulin-Secreting Cells/immunology
    Language English
    Publishing date 2021-07-03
    Publishing country Germany
    Document type Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2021.101283
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  9. Article ; Online: Chronic marijuana usage by human pancreas donors is associated with impaired islet function.

    Qi, Meirigeng / Kaddis, John S / Chen, Kuan-Tsen / Rawson, Jeffrey / Omori, Keiko / Chen, Zhen Bouman / Dhawan, Sangeeta / Isenberg, Jeffrey S / Kandeel, Fouad / Roep, Bart O / Al-Abdullah, Ismail H

    PloS one

    2021  Volume 16, Issue 10, Page(s) e0258434

    Abstract: We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non- ...

    Abstract We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non-users. The islets from marijuana-users displayed reduced insulin secretion as compared to islets from non-users upon stimulation with high glucose (AUC, 3.41 ± 0.62 versus 5.14 ±0.47, p<0.05) and high glucose plus KCl (AUC, 4.48 ± 0.41 versus 7.69 ± 0.58, p<0.001). When human islets from chronic marijuana-users were transplanted into diabetic mice, the mean reversal rate of diabetes was 35% versus 77% in animals receiving islets from non-users (p<0.01). Immunofluorescent staining for cannabinoid receptor type 1 (CB1R) was shown to be colocalized with insulin and enhanced significantly in beta cells from marijuana-users vs. non-users (CB1R intensity/islet area, 14.95 ± 2.71 vs. 3.23 ± 0.87, p<0.001). In contrast, CB1R expression was not co-localized with glucagon or somatostatin. Furthermore, isolated islets from chronic marijuana-users appeared hypertrophic. In conclusion, excessive marijuana use affects islet endocrine phenotype and function in vitro and in vivo. Given the increasing use of marijuana, our results underline the importance of including lifestyle when evaluating human islets for transplantation or research.
    MeSH term(s) Animals ; Cannabis ; Diabetes Mellitus, Experimental ; Mice
    Language English
    Publishing date 2021-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0258434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pancreatic duct hyperplasia/dysplasia in type 1 diabetes and pancreatic weight in individuals with and without diabetes. Reply to Kobayashi T, Aida K, Fukui T et al [letter] and Saisho Y [letter].

    Campbell-Thompson, Martha L / Schatz, Desmond A / Kaddis, John S / Atkinson, Mark A

    Diabetologia

    2016  Volume 59, Issue 4, Page(s) 870–872

    MeSH term(s) Diabetes Mellitus, Type 1 ; Humans ; Hyperplasia ; Pancreas ; Pancreatic Diseases ; Pancreatic Ducts ; Pancreatic Neoplasms ; Pancreatitis
    Language English
    Publishing date 2016-04
    Publishing country Germany
    Document type Comment ; Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1694-9
    ISSN 1432-0428 ; 0012-186X
    ISSN (online) 1432-0428
    ISSN 0012-186X
    DOI 10.1007/s00125-016-3889-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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