**11. Beta cell regeneration**

The traditional generally accepted view is that when a patient gets Type 1 diabetes there is no longer any capacity of the beta cells to regenerate. However, there are almost no studies on beta cell regeneration in humans. In recent years some studies suggest that the old paradigm may be wrong and that beta cells in fact can regenerate. GLP-1 might stimulate beta cell re‐ generation.and GLP-1 agonist (Exenatide) in combination with monoclonal antibodies inter‐ fering with IL-2 ( Daclizumab) was given to patients with longstanding Type 1 diabetes with

some residual insulin secretion, to see whether the treatment could increase C-peptide, but in this study the result was negative [84].

to go to sites of inflammation. However, there is a great gap between studies in animals and and in vitro mechanistic studies, to clinical studies in humans. Recently at the Congress of American Diabetes Association and at the Immunology Diabetes Society the results of two trials blocking the effect of IL-1 in Type 1 diabetes failed. Thus, the use of IL-1r-antagonist showed no effect on preservation of C-peptide or any related clinical parameter[91], and the same was unfortunately the case in another Phase II trial using a IL-1 antagonist, Anakinra [92]. Furthermore blocking IL-1 caused adverse events. Thus, as single therapy using anti-inflam‐ matory drugs is not good enough, but should be tested in combination with other therapies.

Immune Intervention in Type I Diabetes Mellitus

http://dx.doi.org/10.5772/52801

505

No single therapy has shown to be an effective immune intervention in manifest Type 1 dia‐ betes for preservation of residual insulin secretion. As well as successful treatment of child‐ hood leukemia and cancers needed combination of several drugs, it will most probably be necessary to use combination therapies also for Type 1 diabetes. Auto-antigen treatment will probably be part of such future clinical treatment and/or prevention of Type 1 diabetes. Even though GAD-alum so far has not shown any stable efficacy, and Diapep 277 has shown slight efficacy only in adults with good C-peptide preservation, future studies will tell us how to use auto-antigen therapy more effectively, and then in combination with other therapiesIt may be so that treatment with GAD may be useful in patients with immune recognition of GAD, and treatment with proinsulin or insulin/insulin chains may be useful in patients whose immune system recognizes these auto-antigens. Furthermore, the effect might be improved by combi‐ nation therapies with eg Vitamin D, anti-inflammatory drugs, perhaps also in combinations with monoclonal antibodies. New ways of administration may be important and/or DNAvaccines may be found to be another effective way of creating tolerance against auto-antigens,. In spite of recent failures of some immune interventions in clinical trials knowledge is growing

Diamyd Medical was sponsor for the Phase II/III GAD-alum trials and has also given financial support for the investigator-initiated mechanistic studies of this type of therapy. Honorarium for lectures has been received from NovoNordisk, Lilly and SanofiAventis. The author is also

In addition to the author the Linköping Diabetes Immune Intervention study group consists of Ass.professor Rosaura Casas, PhD, Stina Axelsson PhD, Mikael Cheramy PhD,and PhD

**14. Future perspectives of immune intervention**

and there may soon be a breakthrough.

member of Advisory Board of LifeScan.

students Mikael Pihl and Linda Åkerman.

**15. Disclosure**

**Acknowledgements**

Administration of INGAP (islet neogeneis associated protein)in anaimals has caused increased beta cell mass and reversal of hyperglycemia, and hopefully INGAP has regenerating capacity in humans. Daily introductionf of INGAP or placebo has been tried in a double-blind random‐ ized trial in both Type 1 and Type 2 diabetic patients [85], and it showed increased argininstimulated C-peptide during the treatment period, but the effect was very short. Already after 30 days the effect was lost, which does not indicate any influence on beta cell mass as such an effect should have been much longer
