Centre of reference

As a national diabetes centre and as a EU “Centre of Reference” Diabeter is closely involved in scientific research. It also initiates scientific research. Our research topic is closing the loop.

“Closing the loop” is often interpreted as the development of an artificial pancreas: a system that automatically regulates the glucose measurement and insulin administration. This is an important step in the right direction, but we have to do more than that. Improving the treatment now, the effect this has on diabetes and eventually finding the cure are what we really talk about when we talk about closing the loop. Diabeter wants to do all of this and this is what our research is about.

Research on better adjustment of the insulin pump, a better combination with the continuous glucose sensor, research on what makes high-tech successful and how we can get it to as many patients as possible, plus the role of psychosocial factors in reaching the goal of successful diabetes treatment: it’s all part of the deal for us.

Cure for type 1 diabetes and prevention

Research on early use of treatments that restore the immune system, both shortly after the occurrence of type I diabetes and later on is one of our goals. It helps to shed a light on the individual aspects of the disease and the fault in the immune system, to help find the best combination of ways to interfere in the immune system. With the ultimate goal to prevent and cure type I diabetes.

Early detection, prevention and better treatment of the effects of diabetes

Research on the early detection of damage and damage processes to organs that can be damaged by diabetes and combining this knowledge with hereditary and social factors is another research effort. The knowledge it brings can be applied to measure damage to the nerves, retina, kidneys et cetera, to measure the effects on blood vessels and early signs of aging through diabetes.

New technological developments

New developments in the technology of insulin pumps and glucose sensors help to bring a “closed loop”-system nearer to the market. New technology gives us the possibility to take care to a higher level. At Diabeter we participate in research that brings this technology one step closer.

State of affairs 2014

In curing diabetes two steps are necessary: repairing the mistake in the immune system (that destroyed the insulin cells) and making new cells that produce insulin. As far as the first step goes, we are at the start of a new phase. After we have had to invest for many years in understanding the mistake in the immune system that causes diabetes, we are now in the process of the first experimental trials in people (over 12 years of age) to reverse the process. Before this, we mainly did animal tests that looked promising, but a man is not a mouse. We have now finally started an important future development, even if only “experimental”.

We are still in the process of finding out much about the activity and safety before treatment in this way can become the new standard. But still this research is a step towards the ultimate cure that lies somewhere on the horizon (ten to fifteen years, until then we will have to make due with technological developments that make diabetes treatment better and easier with for instance pumps and continuous sensors). This kind of research is very much an international effort. It is the only way to bring together enough people to get the right answers to our questions within an agreeable time-frame. At Diabeter we do a lot of this kind of research, in collaboration with groups in Leiden (prof Bart Roep), San Francisco and Brussels/Leuven, supported by national (Diabetesfonds, JDRF) and international funds (JDRF and EU).

With this kind of research we hope to be of value not only to people who have just developed type I diabetes. The ultimate goal is to come up with a cure for everyone with the disease. Research is now mostly done in patients who have recently been diagnosed. The reason for this is that their pancreas still produces insulin, which makes it easier to measure the effect of our experimental treatment. If it works the patients’ insulin production has to remain intact to a certain extent (measured by so-called C-peptide, a part of insulin that is not present in insulin “from a bottle”).

Our participation in three research projects has now ended as they are in the follow-up phase. One is a vaccine study with a protein that is also a part of the insulin producing beta cell (GZD65: Diamyd study). The second is a study in which a “slowing-down” antibody is administered (Anti-CD3:  DEFEND-2 trial to start (www.defendagainstdiabetes.com). The third is the Protege study (www.macrogenics.com). These studies are based on the finding that having the mistake in the immune system is not so much of a problem, but that the real problem is the inability of the body to recover such a mistake, thus allowing the “wrong” defence cells to do their work in destroying the insulin cells. We don’t have to know what exactly the cause is, but we are able now to make so-called “correcting” (regulating T-cells, T-regs) cells through vaccination of administering antibodies. They more or less correct the mistake by recovering the balance between “aggressive” and “slowing-down” antibody.

The first results from this study are not overly positive. If we compare the group of patients that have been treated with the patients who received a placebo the difference is not very big. But there is a number of children who respond very good to the treatment and who barely need insulin two years later, much less than expected and in comparison to the control group. All these studies seem to show success factors. Together with Bart Roep we are now finding out what those factors are and which ones give the best results.

Other studies we are involved in (but in which patients cannot be included yet) concern research on vaccines that can be inhaled through the nose with fragments of insulin (Pre-point study: http://www.diabetes-point.org/uk.html) and recovery of defence with vitamin D like matter (part of the NAiMIT study http://naimit.eu/).
(More information about studies: http://clinicaltrials.gov/ct2/results?term=type+1+diabetes)

Concerning the making of new insulin cells, the second step in curation, we know that our earliest thoughts on this subject – that the body is unable to make new cells once the old ones are broken – is (luckily) incorrect. Making new ones is possible, but it is a slow process and once these cells are developed they can still be destroyed by the defence mechanism as long as the failure in this system exists. It is possible yet to produce extra insulin cells from someone’s stem cells and with medication, but not in high enough quantities and fast enough for recovery. This research is important because transplantation is no option. Insulin cells from a donor will also be attacked by the body’s defence mechanism (which means a high dose of medicine to slow this down). Besides, the number of insulin cells needed from donors will not be sufficient.

Until curation becomes available – which will take some doing yet – we will have to rely on new pump and sensor technology to make treatment better. This is important right from the start of someone’s diabetes. Good measurement in this “honeymoon”-phase gives the body’s immune factory a rest so that it will last longer and is less influenced by the mistake in the defence mechanism. It is important in this phase to learn how to deal with diabetes, to not let it become the “boss”, but to learn how to act like a pancreas. By adjusting the pump correctly and “acting as” the pancreas we can reach a better regulation – even in small children – than we were able to do a few years back. Use of a continuous glucose sensor (that continuously measures glucose value, not in the blood but in the fat tissue under the skin) can improve this further. We’re not there yet, but the future has started.