Table 2.
New therapeutic interventions for Type 1 diabetes in humans
| Aim of intervention | Type of intervention | Pros/advantages | Cons/disadvantages | |
|---|---|---|---|---|
| Prevention of B-cell loss | Immune-based therapy | Antigen specific | ||
| Insulin, HSP60, GAD65 (and their peptides) | Safe Induction imunoregulatory mechanisms Moderate clinical benefit (preservation of C-peptide over a limited time period) in intervention trials | No/partial success in prevention trials so far | ||
| Non-antigen specific | ||||
| Immunosuppresants | Induce depletion/inactivation of pathogenic cells | Limited/no effect; short- and long-term side effects | ||
| Nicotinamide | Safe Protection against B-cell death | No efficacy for diabetes prevention | ||
| Anti-CD3 mAb | Induction of tolerance by apoptosis/ anergy of activated T cells and expansion of Tregs No chronic immunosuppression | Side effects (moderate cytokine release syndrome; transient reactivation of EBV; potential anti-idiotypic antibodies) | ||
| Prevention of loss of insulin production > 1 year in intervention trials | Reoccurrence of B-cell failure | |||
| Regeneration/restoration of B-cell mass | Transplantation | Pancreas/islet cells | Feasible Improved glycaemic control Preferable in simultaneous renal graft (when immunosuppression is already necessary) | Modest success of the procedure; continuous immunosuppression is needed Islet isolation procedure—technically challenging; costly; lack of sufficient pancreata (multiple donors per recipient) Whole pancreas—more invasive surgery |
| Pharmacologic agents (e.g. GLP-1 receptor agonists, DPP-4 inhibitors) | Approved for Type 2 diabetes therapy Eliminate need for surgical procedures Presumably stimulates B-cell regeneration | Definite effect of B-cell regeneration not yet fully evaluated Long-term safety needs further evaluation | ||
| Stem cells/genetic therapy | Good potential source of surrogate insulin producing cells | Still in preclinical research phase | ||
DPP-4, dipeptidyl peptidase 4; EBV, Epstein–Barr virus; GLP-1, glucagon-like peptide 1; mAb, monoclonal antibody; Tregs, regulatory T cells; HSP, heat shock protein; GAD, glutamic acid decaboxylase.