Type 1 diabetes as an autoimmune disease: the evidence

Paschou, Stavroula Α.; Petsiou, Asimina; Chatzigianni, Katerina; Tsatsoulis, Agathocles; Papadopoulos, George K.

doi:10.1007/s00125-014-3229-5

Cited by 24 publications

(17 citation statements)

References 15 publications

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“…In addition, the HLA allele DQB1*0602 provides protection against T1DM development. This allele is present in approximately 20% of the general US population but only in 1% of the children who have developed T1DM ( 1 , 11 , 12 , 13 ).…”

Section: Genetic Factorsmentioning

confidence: 99%

“…In recent years, it has been demonstrated that the subpopulation of T regulatory lymphocytes (Tregs, formerly known as suppressive lymphocytes) plays an important role in the immune response network, especially for peripheral tolerance. It has been found that patients with T1DM present quantitative and qualitative deficits in Tregs, which may explain the increased (without limits) immune response, which eventually leads to the autoimmune response ( 1 , 23 , 58 , 59 ).…”

Section: Immunologic Factorsmentioning

confidence: 99%

“…Other theories suggest that apoptosis is induced directly by contact of autoreactive T lymphocytes with β cells via the perforating system or Fas/Fas ligand interaction. Even in this case, cytokines’ secretion disorder is required ( 1 , 2 , 8 , 60 , 61 , 62 ). The subpopulation of Tregs is of great interest and their quantitative and qualitative deficits in patients with the disease are very important ( 58 , 59 ).…”

Section: Immunologic Factorsmentioning

confidence: 99%

“…T1DM results from the autoimmune destruction of β cells of the endocrine pancreas. A small percentage of affected patients (<10%) are classified as type 1B, with no evidence of autoimmunity and the pathogenesis in these cases is considered idiopathic ( 1 , 2 ). The aim of this comprehensive review is to present updated information on the pathogenesis of T1DM.…”

Section: Introductionmentioning

confidence: 99%

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On type 1 diabetes mellitus pathogenesis

Paschou

Papadopoulou-Marketou

Chrousos

et al. 2018

Endocrine Connections

197

122

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Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident.

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Section: Genetic Factorsmentioning

confidence: 99%

Section: Immunologic Factorsmentioning

confidence: 99%

Section: Immunologic Factorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

On type 1 diabetes mellitus pathogenesis

Paschou

Papadopoulou-Marketou

Chrousos

et al. 2018

Endocrine Connections

197

122

View full text Add to dashboard Cite

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“…Type 1 diabetes (T1D) is a metabolic disorder characterized by chronic hyperglycemia and alterations in carbohydrate, lipid and protein metabolism. It develops because of an autoimmune response against pancreatic β-cells which leads to failed insulin production 1 . According to estimates, the incidence of type 1 diabetes is increasing by around 3–4% every year, particularly among children 2 , 3 .…”

Section: Introductionmentioning

confidence: 99%

Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase products

Ramalho

Filgueiras

Silva-Jr

et al. 2018

Sci Rep

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Type 1 diabetes is associated with systemic low grade inflammation (LGI). We have previously shown that LGI in diabetic mice depends on systemic circulation of leukotriene (LTB4) which potentiates the toll-like/IL1β receptors response in macrophages. Impaired wound healing is an important co-morbidity in diabetes, and macrophages play a key role in this process. Here, we investigated the role of leukotrienes on monocytes and macrophages phenotype and in the impaired wound healing in diabetic mice. Type 1 diabetes was induced with streptozotocin in 129SvE wild-type (WT) and leukotrienes-deficient 5LO−/− (5-lipoxygenase knockout) mice. In diabetics, the systemic levels of LTB4, TNF-α, IL-6, IL-10, IL-12 and IFNγ were increased as well as the frequency of pro-inflammatory monocytes (CD11b+Ly6ChighLy6G−) compared to healthy mice. In diabetic 5LO−/− mice, these parameters were similar to those in healthy mice. Resident peritoneal macrophages from diabetic WT mice showed a classically activated M1-like phenotype (high Nos2, Stat and Il12 expression, and nitrite levels). Macrophages from diabetic 5LO−/− mice presented alternatively activated M2-macrophages markers (high Arg1 and Chi3l3 expression and arginase activity) and when stimulated with IL4, enhanced phosphorylated-STAT6. Cutaneous wound healing in diabetic WT mice was impaired, which correlated with the decreased frequency of M2-macrophages (CD45+F4/80+CD206+) in the lesions. In diabetic 5LO−/− mice, the frequency of M2-macrophages in the wound was similar to that in healthy mice, suggesting that the impaired healing of diabetic mice depends on 5LO products. The inhibition of leukotrienes or antagonism of its receptors could be a therapeutic alternative for diabetic patients with impaired healing.

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