Type 1 diabetes mellitus occurs in genetically predisposed persons as a consequence of the immune-mediated destruction of pancreatic islet beta cells that secrete insulin.  The onset of clinically overt diabetes represents the end point of an insidious, progressive decline in the function of beta cells after the majority of beta cells have been damaged or destroyed. Risk can be predicted on the basis of immunologic markers and tests of beta-cell function. Polydipsia, polyphagia, and polyuria (the classic trio of symptoms associated with disease onset) along with overt hyperglycaemia remain diagnostic hallmarks in children and adolescents, and to a lesser extent in adults. An immediate need for exogenous insulin replacement is also a hallmark of type 1 diabetes, for which lifetime treatment is needed. Key questions remain regarding the epidemiology of type 1 diabetes, effectiveness of current therapies, understanding how the disorder develops, and preventing or curing the disease.
The incidence of type 1 diabetes has been increasing worldwide for several decades.  In Finland, Germany, and Norway, annual increases in incidence of 2.4%, 2.6%, and 3.3%, respectively, have been reported.  ,  ,  A plethora of environmental influences have been purported to affect the epidemiology of type 1 diabetes, with infant and adolescent diets, vitamin D and vitamin D pathway constituents, and viruses receiving the most focus. Interest is growing in models to describe the influence of environment on type 1 diabetes, including the hygiene hypothesis and gut microbiome; however, no specific agents with an unequivocal influence on pathogenesis have been identified.  ,  ,  ,  ,  ,  ,  Most research articles on the pathogenesis of type 1 diabetes begin by noting that the disorder results from an autoimmune destruction of insulin-secreting pancreatic β cells. The presence of a chronic inflammatory infiltrate that affects pancreatic islets at symptomatic onset of type 1 diabetes is the basis of this observation. 
There is relatively good evidence from human studies that natural killer (NK) T cell activity, APC function as well as generation of CD25+ regulatory lymphocytes are all reduced in human diabetic patients.  This finding, coupled with strong evidence from animal models that enhancing NK T cell activity  , systemic infections leading to immune activation or transfer of CD25+ cells  can prevent T1DM, makes generalized immune dysregulation a likely underlying cause for T1DM. Genetic factors and environmental influences might all be able to enhance or alleviate this systemic dysregulation. It is intriguing that most defects that have been found constitute a lack of certain immune functions including generation of molecules such as interferons by NK T cells that are known to be detrimental to islets. However, lack of NK T cell activity also results in less interleukin (IL)-4 production and, consequently, lower degrees of APC activation, that might result in lower levels of CD25+ or T helper 2-like regulatory cells than needed to maintain a healthy immune equilibrium. Therapeutically, this situation might be exploited, but one will have to act with caution, because any type of systemic correction will affect other immune functions, such as host defense.
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