Type 1 diabetes

Atkinson, Mark A.; Eisenbarth, George S.; Michels, Aaron

doi:10.1016/s0140-6736(13)60591-7

Cited by 2,100 publications

(1,665 citation statements)

References 154 publications

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“…A typical de novo T1D patient presents with hyperglycemia and polyuria, polydipsia and weight loss. Ketoacidosis is common and Ab status at the moment of T1D diagnosis should be verified [21,22,23,24,25,26,27,28,29,30]. …”

Section: Type 1 Diabetesmentioning

confidence: 99%

Celiac Disease and Endocrine Autoimmunity

Kahaly¹,

Schuppan²

2015

Dig Dis

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Background: Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Key Messages: Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. Conclusions: The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives.

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Section: Type 1 Diabetesmentioning

confidence: 99%

Celiac Disease and Endocrine Autoimmunity

Kahaly¹,

Schuppan²

2015

Dig Dis

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“…Type 1 diabetes (T1D) results from autoimmune-mediated destruction and dysfunction of insulin-producing pancreatic β cells (1). Prior to the onset of T1D, genetically susceptible individuals develop islet autoantibodies, often during the first few years of life.…”

Section: Introductionmentioning

confidence: 99%

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes

Mehdi¹,

Hamilton‐Williams²,

Cristino³

et al. 2018

JCI Insight

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“…In T1D, genetic mutations of human leucocyte antigen (HLA) are the most common variants,3 while also virus infections have been implicated in T1D development 3. The application of genome‐wide association studies (GWAS) has identified over 50 gene variants associated with T2D 2, 4.…”

Section: Introductionmentioning

confidence: 99%

Decreased levels of keratin 8 sensitize mice to streptozotocin‐induced diabetes

et al. 2018

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AimDiabetes is a result of an interplay between genetic, environmental and lifestyle factors. Keratin intermediate filaments are stress proteins in epithelial cells, and keratin mutations predispose to several human diseases. However, the involvement of keratins in diabetes is not well known. K8 and its partner K18 are the main β‐cell keratins, and knockout of K8 (K8−/−) in mice causes mislocalization of glucose transporter 2, mitochondrial defects, reduced insulin content and altered systemic glucose/insulin control. We hypothesize that K8/K18 offer protection during β‐cell stress and that decreased K8 levels contribute to diabetes susceptibility.MethodsK8‐heterozygous knockout (K8+/−) and wild‐type (K8+/+) mice were used to evaluate the influence of keratin levels on endocrine pancreatic function and diabetes development under basal conditions and after T1D streptozotocin (STZ)‐induced β‐cell stress and T2D high‐fat diet (HFD).ResultsMurine K8+/− endocrine islets express ~50% less K8/K18 compared with K8+/+. The decreased keratin levels have little impact on basal systemic glucose/insulin regulation, β‐cell health or insulin levels. Diabetes incidence and blood glucose levels are significantly higher in K8+/− mice after low‐dose/chronic STZ treatment, and STZ causes more β‐cell damage and polyuria in K8+/− compared with K8+/+. K8 appears upregulated 5 weeks after STZ treatment in K8+/+ islets but not in K8+/−. K8+/− mice showed no major susceptibility risk to HFD compared to K8+/+.ConclusionPartial K8 deficiency reduces β‐cell stress tolerance and aggravates diabetes development in response to STZ, while there is no major susceptibility to HFD.

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Type 1 diabetes

Cited by 2,100 publications

References 154 publications

Celiac Disease and Endocrine Autoimmunity

Celiac Disease and Endocrine Autoimmunity

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes

Decreased levels of keratin 8 sensitize mice to streptozotocin‐induced diabetes

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