Introduction
Hallmarks of type 1 diabetes pathogenesis
The nature of early disease may be cyclical and relapsing–remitting
The distribution of the disease is not homogeneous
How can the histopathological hallmarks of diabetes be explained by viral infection?
Reference | Virus | Main message |
---|---|---|
Rasmussen et al, 2011 [90] | Respiratory viruses | Respiratory infections more common in children who later progress to type 1 diabetes. |
Beyerlein et al, 2013 [91] | Respiratory viruses, not classified | Increased hazard ratio of islet autoantibody seroconversion is associated with respiratory infections during the first 6 months of life. |
Gale, 2008 [92] | Rubella | Congenital rubella may predispose to subsequent autoimmunity but existing studies are weak. |
Viskari et al, 2003 [93] | Rubella | No evidence of increased frequency of markers for humoral beta cell autoimmunity in patients with congenital rubella syndrome. |
Green et al, 2004 [94] | CVB | Review of 26 case–control studies: no convincing evidence for or against an association between CVB infection and type 1 diabetes. |
Stene et al, 2010 [65] | EV | Progression from islet autoimmunity to type 1 diabetes may increase after an EV infection characterised by the presence of viral RNA in blood. |
Tapia et al, 2011 [95] | EV | No support for faecal shedding of enteroviral RNA as major predictor of advanced islet autoimmunity. |
Yeung et al, 2011 [96] | EV | Clinically significant association between EV infection, detected with molecular methods, and autoimmunity/type 1 diabetes. |
Salur et al, 2011 [97] | EV | Nested case–control study where all case children have progressed to type 1 diabetes. EV RNA-positive samples were more frequent among the cases than among the controls. |
Oikarinen et al, 2012 [98] | EV | Large proportion of type 1 diabetes patients have prolonged/persistent EV infection associated with an inflammation process in gut mucosa. |
Mercalli et al, 2012 [99] | EV | Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 controls and 27 individuals with coeliac disease analysed for the presence of EV RNA by in situ hybridisation and RT-PCR. Prolonged/persistent EV infections in gut mucosa are not common in patients with type 1 diabetes. |
Viskari et al, 2000 [100] | EV | The rapid decrease in EV infection frequency in Finland may explain the increasing incidence of type 1 diabetes. |
Roivainen et al, 2002 [101] | EV | Patterns and consequences of EV infections investigated in cultured adult human isolated islets. The capacity of EV to kill human beta cells or impair their function is not solely defined by the serotype, but also by as yet unidentified characteristics of the virus strain involved. |
Viskari et al, 2004 [102] | EV | EV antibodies less frequent in countries with high diabetes incidence compared with countries with low diabetes incidence. |
Viskari et al, 2005 [103] | EV | Maternal EV antibodies analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden. A low frequency of EV infection in the background population increases the susceptibility of young children to the diabetogenic effect of EV. |
Richardson et al, 2009 [104] | EV | EV capsid protein VP1 is commonly found in the islets of recent-onset type 1 diabetic patients, but only rarely in normal paediatric controls. |
Gamble et al, 1973 [105] | CVB4 | Antibody to CVB4 virus more often found in diabetic patients than in controls, particularly in the 10–19 year age group. |
Gamble et al, 1969 [106] | EV | In patients with recent-onset diabetes, no evidence was found of any excess of antibodies to mumps virus or certain common respiratory viruses. However, those diabetics patients who developed insulin dependence within 3 months of onset were found to have higher antibody titres to CVB4. |
Dotta et al, 2007 [107] | EV | Pancreatic tissue from six type 1 diabetic and 26 control organ donors analysed via immunohistochemistry, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture and immunological studies. CVB4 found in specimens from three of the six diabetic patients. |
Laitinen et al, 2013 [62] | CVB1, B3, B6 | 183 children who persistently tested positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. CVB1 was associated with an increased risk of beta cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk. |
Oikarinen et al, 2014 [61] | CVB1 | 249 children with newly diagnosed type 1 diabetes and 249 control children matched according to sampling time, sex, age and country recruited in Finland, Sweden, England, France and Greece between 2001 and 2005 (mean age 9 years; 55% male). Antibodies against CVB1 were more frequent among diabetic children than among control children. |
Cabrera-Rode et al, 2003 [108] | Echovirus 16 | The occurrence of a large-scale echovirus 16 epidemic was associated with the appearance of humoral autoimmune markers of type 1 diabetes. Echovirus 16 infection might be capable of inducing a process of autoimmune beta cell damage. |