Table 2. Overview of Ag-based approaches as an intervention or prevention therapy for T1D in humans.
| Ag | Study name | Treatment | Subjects | Clinical or immunological outcome | Reference |
|---|---|---|---|---|---|
| insulin |
DPT-1 parenteral arm |
0.25 U/kg/d sc + 4 d continuous infusion/y |
• T1D relatives • ICA+ • 5-y risk > 50% |
No effect | 97 |
| Insulin | Diabetes subcutaneous prevention trial in high risk relatives | 2 × 0.05 U/kg/d Sc |
• 5–39 y • IA-2 Ab+ • No protective haplotype |
No effect | 98 |
| Insulin |
DPT-1 oral arm |
7.5 mg po |
• T1D relatives • ICA+ • 5-y risk 26–50% |
IAA ≥80 nU/ml delay onset | 99 |
| Insulin | EPPSCIT (European prediabetes prevention-sc insulin trial) | 0.2 U/d sc |
• T1D relatives • ICA+ |
No effect | 100 |
| Insulin | ORALE | 2.5 or 7.5 mg/d po |
• 7–40 y • auto-Ab+ • <2 w diagnosed |
No effect | 101 |
| Insulin | IMDIAB VII | 5 mg/d po |
<4 w diagnosed | No effect | 102 |
| Insulin | Oral insulin | 1 or 10 mg/d po |
• ICA+ • <4 w diagnosed |
>20 y (+ normal baseline C-peptide) slower C-peptide loss no clinical benefit |
103 |
| Insulin |
DIPP (T1D prediction and prevention study) |
1 U/kg/d intranasal |
≥2 auto-Abs | No effect | 104 |
| insulin |
INIT (intranasal insulin trial) |
40 U/d first 10 d, then 80 U/w 12 mo intranasal |
• <12 mo diagnosed • 30–75 y • GADA+ • fasting C-peptide ≥ 0.2 nM |
Tolerance induction but no clinical effect | 105 |
| GAD-Alum | Subcutaneous GAD65 | 4, 20, 100 or 500 μg w 1 and w 4 sc |
• LADA patients, • 30–70 y |
20 µg; ↑ fasted and stimulated C-response | 106 |
| GAD-Alum | Swedish Diamyd | 20 μg d 1 and d 30 sc |
• 10–18 y • <18 mo diagnosed • GADA+ • fasting C-peptide >0.1 nM |
<6 min diagnosed: ↑ fasted and stimulated C-response (30 min) | 107 |
| GAD-Alum | TrialNet GAD study | 2 or 3 × 20 µg at d 1, 4 w and 12 w sc |
• 3–45 y • <100 d diagnosed • GADA+ • stimulated C-peptide >0.2 nM |
No effect | 108 |
| GAD-Alum | EU Diamyd | 2 or 4 × 20 μg at d 0, d 30, d 90 and d 270 sc |
• 10–20 y • <3 min diagnosed • GADA+ • fasting C-peptide >0.1 nM |
No effect | 109 |
| DiaPep277 (HSP60) |
Trial 420 | 1 mg at entry, 1, 6 and 12 m sc |
• Men • 16–58 y • <6 mo diagnosed • basal C-peptide >0.1 nM |
Stable C-peptide response | 136 |
See Table 4. GAD65, glutamic acid decarboxylase 65; HSP60, heat shock protein 60; sc, subcutaneous; y, years; ICA, islet cell antibody; mo, months; d, day; GADA, GAD-associated antibodies; LADA, latent autoimmune diabetes in adults; w, weeks; po, per os.