Table 2.
Summary of molecular studies investigating type 1 diabetes (T1DM) and enteroviruses
| Study | Country | Cases/controls | Cases and details of diabetes | Age of cases (years unless specified) | Controls | Method of detection | EV type sequenced |
|---|---|---|---|---|---|---|---|
| Andreoletti, 199714 | France | 12/15 | Newly diagnosed with metabolic decompensation | Mean 28.2 (SD 10.4) | Healthy adults | EV RNA in peripheral blood (RT PCR) | CVB-3, CVB-4 |
| Previously diagnosed with metabolic decompensation | Mean 32.6 (SD 13.3) | ||||||
| Buesa-Gomez, 199460 | USA | 2/5 | Fatal acute onset | 14 months and 3 years | Children who died from non-diabetic causes | Coxsackie RNA in autopsy pancreatic samples (RT PCR) | — |
| Clements, 199541 | UK | 14/45 | Newly diagnosed | Mean 3.9, range 1.4-6.0 | Normal subjects matched for age, sex, sample date, and place | EV RNA in serum (RT PCR) | CVB-3, CVB-4 |
| Coutant, 200232 | France | 16/49 | Newly diagnosed (within 1 month of diagnosis) | Range <6 | Healthy children matched for age, sex, sample date, and place | EV RNA in serum (RT PCR) | — |
| Craig, 200358 | Australia | 206/160 | Newly diagnosed (within 2 weeks of diagnosis) | Median 8.2, range 0.7-15.7 | Children without diabetes from community | EV RNA in plasma or stool samples (RT PCR) | EV-71 |
| Dahlquist, 200436 | Sweden | 600/600 | Eventual diabetes, on Swedish childhood diabetes register | Neonate | People without diabetes from same biobank | EV RNA in newborn blood spots (RT PCR) | — |
| Dotta, 200746 | Italy | 6/26 | Recent onset | Range 14-50 | Normal multi-organ donors | EV vp1 immunostaining in autopsy pancreatic samples (Dako anti-vp1) | CVB-4 |
| Foulis, 199038 | UK | 147/43 | 88 recent onset (duration <1 year), 59 established (duration 1-19 years) | Range 1-37 | Normal autopsy pancreases from 11 neonates, 21 children, 11 adults | EV vp1 immunostaining in autopsy pancreatic samples | — |
| Foy, 199535 | UK | 17/42 | Newly diagnosed (on day of diagnosis) | Median 11, range 2-35 | Patients without diabetes, matched for age and sex | EV RNA in peripheral blood (RT PCR) | — |
| 38/42 | Duration 2 months-10 years | Median 11, range 3-16 | |||||
| Kawashima 200461 | Japan | 61/58 | Type 1 diabetes | Range 9 months - 40 years | Healthy people | EV RNA in serum (RT PCR) | CVB-2, CVB-3, CVB-4, CVB-5 |
| Lönnrot, 200031 | Finland | 11/34 | Eventual diabetes, from DiMe Study | Mean 8.4, range 2.6-17 | Children from same study cohort who did not develop T1DM or autoantibodies | EV RNA in serum (RT PCR) | — |
| 47/34 | Newly diagnosed | Mean 4.4 | |||||
| Maha, 200334 | Egypt | 40/30 | Recent onset (<1 year) | Mean 11.30 (SD 2.16) | Normal healthy children | EV RNA in serum (RT PCR via tissue culture) | CVB-4, CVB-6 |
| 30/30 | Duration >1 year | Mean 11.80 (SD 2.70) | |||||
| Moya-Suri, 200533 | Germany | 47/50 | Newly diagnosed (median 5 days from diagnosis) | Median 13, IQR 11-15 | Children from same study negative autoantibodies | EV RNA in serum (RT PCR) | CVB-4, CVB-2, CVB-6 |
| Nairn, 199912 | UK | 110/182 | Newly diagnosed (within 1 week from diagnosis) | Mean 7.1, range 3 months-16 years | Children without diabetes (matched for age, location, time of sampling) | EV RNA in serum (RT PCR) | PV1-3, CVA-21, CVA-24, EV-70 |
| Oikarinen, 200739 | Finland | 12/10 | Established (duration 0-51 years, median 13) | Median 30, range 18-53 | Patients without diabetes from same hospital department | vp1 immunostaining in small bowel mucosa (Dako anti-vp1) | — |
| Richardson, 200917 | UK | 72/119 | Recent onset (8.2 (SD 4.1) months from diagnosis) | Mean 12.65 (SD 1.1), range 1-42 | Normal autopsy pancreases from 11 neonates, 39 children and 69 adults | EV vp1 immunostaining in autopsy pancreatic samples (Dako anti-vp1) | — |
| Sarmiento, 200716 | Cuba | 34/68 | Newly diagnosed (0.78 (SD 2.4) days from diagnosis) | Mean 7.3 (SD 4.5), range 1-15 | Healthy subjects, verified ICA negative and no family history of diabetes | EV RNA in serum (RT PCR) | — |
| Schulte, 201043 | Nether-lands | 10/20 | Newly diagnosed (within 1 month of diagnosis) | Mean 9.7, range 5-14 | Children of same age range in hospital with non-endocrine disorders | EV RNA in peripheral blood mononuclear cells (RT PCR) | HEV-B |
| Toniolo, 201044 | Italy | 112/58 | Newly diagnosed | Mean 6.8, median 9.0, range 2-16 |
Healthy children | EV RNA in peripheral blood (RT PCR) | HEV-A, HEV-B, HEV-C, HEV-D |
| Yin, 200240 | Sweden | 24/24 | Newly diagnosed (within 1 week from diagnosis) | Mean 8.4, range 1.6-15.7 | Healthy children from nearby counties | EV RNA in PBMCs (RT PCR) | CVB-5, EV-5, CVB-4 |
| Ylipaasto, 200442 | Finland/ Germany | 65/40 | Duration: few weeks to 19 years | Range 18-52 | Non-diabetic pancreases (age-sex matched) | EV RNA in autopsy pancreatic samples (RNA probes and in situ hybridisation) | — |
EV RNA=enterovirus RNA; RT PCA=reverse transcription-polymerase chain reaction.