Leaking gut in type 1 diabetes.
OBJECTIVE
Several studies have indicated that children with type 1 diabetes show altered intestinal immune system and, in particular, increased small intestinal permeability. This review discusses the recent research linking the gut and type 1 diabetes, which may reveal novel pathogenic pathways and new possibilities for disease prevention.


RESULTS
Recent studies indicate that not only patients with manifest type 1 diabetes show increased small intestinal permeability and high serum levels of zonulin, that is protein controlling epithelial tight junctions, but prediabetic, normoglycemic individuals with beta-cell autoimmunity show signs of leaking gut. Also studies in BioBreeding-rat model of autoimmune diabetes suggest that high permeability of the intestine precedes autoimmune diabetes. The enteropathy characterized by increased intestinal permeability and inflammation seems to be the basis for the development of beta-cell destruction, as for example zonulin agonist, which decreases the gut permeability, prevents the development of diabetes.


CONCLUSIONS
The leaking gut syndrome with subclinical inflammation is associated with beta-cell autoimmunity and type 1 diabetes. Furthermore, treatment of the leakiness has been reported to modulate development of autoimmune diabetes in animal models suggesting that intestinal environment plays a key role in the destruction of insulin-producing beta-cells in the pancreas.
Vaarala
Outi
O
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland. outi.vaarala@ktl.fi
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000209:etiology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D010539:Permeability; D013577:Syndrome