Simultaneous onset of Type 1 diabetes mellitus in identical infant twins with enterovirus infection

Abstract

This report describes classical Type 1 insulin deficient diabetes mellitus (DM) arising in twins aged 14 months, both of whom had evidence of enterovirus infection. The diagnosis of Type 1 DM was made in the second twin within 12 days of the first. Enterovirus infection was detected in each twin at diagnosis by polymerase chain reaction (PCR). Both twins were negative for enterovirus by PCR 5 months following diagnosis, although both were then positive for islet cell antibodies. Sequencing of the amplicons produced by PCR suggested that the viruses from each twin were not the same but that they were both variants related to echovirus 6.

Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

“…As NOD mice age, naturally occurring, pathogenic autoimmune insulitis develops rapidly (4) with widespread islet inflammation (insulitis) present by week 12 to 15 of age, when T1D also begins to occur. T1D rapidly ensues following inoculation of old (Ͼ12 weeks of age) NOD mice with virulent CVB (14), a model that recapitulates observations of sudden T1D onset in humans reported to occur during or shortly after an infection (37,52). Initiation of rapid T1D onset in older mice also appears to correlate directly with the viral replication phenotype: CVB strains that replicate more rapidly to higher titers in NOD mouse pancreatic tissue initiate rapid T1D onset, whereas viruses which replicate to lower titers do not trigger T1D at rates different from mock-infected animals (14).…”

“…A predisposing, multigenic component has been described but accounts for fewer than 50% of cases (7,35,45); environmental factors (e.g., viral infections) have therefore been proposed to explain the remaining cases of T1D (3,6,32,57,58) that cannot be ascribed solely to host-driven pathogenic autoimmunity. Human enterovirus (HEV) infections have long been suspected as environmental triggers of human T1D (12,22,27); infections by common HEVs, such as the group B coxsackieviruses (CVB 1 to 6) and diverse echoviruses, have been implicated as triggers of T1D onset at the time of or shortly after infection (8,9,13,19,28,37,39,40,42,52,60). Nonetheless, it remains unclear whether HEV initiates T1D in humans (18,21,24,26); evidence supporting an etiologic connection between HEV infection and T1D onset is not as well-established as the links between, for example, specific HEV infections and poliomyelitis, aseptic meningitis, or myocarditis (43).…”

Enterovirus variants in the serum of children at the onset of Type 1 diabetes mellitus

“…This included a pair of twins ( Fig. 2: d twin 1 and d twin 2) who presented with Type 1 DM within 2 weeks of each other [21], in whom the sequences were related but not closely enough to conclude a common source of infection. There was a further pair of unrelated children (Fig.…”

The role of viruses in human diabetes

“…The viruses involved were of coxsackie B type. Using PCR methodology, two 14 month old identical twins infected with echovirus 6 variants acquired diabetes within 12 days of one another [43]. Such cases indicate that infection is likely to have been from a common source within the family.…”