Assessing and predicting functional and quality of life-related outcomes of islet and pancreatic transplantation in patients with type 1 diabetes mellitus

There is need for specific markers to predict pancreas and islet graft function
and damage on the short and long term after pancreas or islet transplantation;
no validated markers currently exist and therefore allograft rejection is
generally not recognized in time. In the long term graft function deteriorates;
we cannot currently predict at which time this happens and the exact cause is
not known. Research is hampered due to lack of data on predictors and aetiology.
Also, clinical pancreas or islet transplantation does not always lead to
insulin independence in patients with type 1 diabetes. Pancreas transplantation
has better long term results concerning insulin independence, but is associated
with more complications on the short term. Islet transplantation has fewer
complications but achieves insulin independence in fewer cases. Despite the
fact that insulin independence is often not achieved in most islet transplant
recipients, there is a large reduction of episodes of severe hypoglycaemia and
fewer diabetes-related complications as compared to before transplantation.
We hypothesize that there will be a clear correlation between marker elevation
and allograft failureFurthermore, we hypothesize that quality of life will improve after both
procedures, possibly more so on the short term for islet transplantation
recipients and more so in the long term for pancreas transplantation recipients

There are two objectives for this study: first, to find specific serum beta
cell damage markers that can serve as a clinical predictive tool for beta cell
allograft loss. Second, to compare quality of life and diabetes-related
outcomes in patients who receive a pancreas versus an islet transplantation at
the LUMC

Prospective observational cohort study
Before and after transplantation (+3, 12, 24, 60 months) allograft function
will be determined with a mixed meal test (MMT). Also urine samples will be
taken for kidney damage markers. Furthermore, three questionnaires will be
administered (for quality of life (SF36), Clarke's hypoglycemia scoring list
and the PAID (psychosocial aspects in diabetes). During follow-up serum markers
for islet damage (micro-RNA panel, C-peptide, PPP1R1A, complement profile) will
be measured in decreasing frequency and correlated to graft function.

The extent of the burden consists of one extra MMT before islet transplantation
for the islet transplant recipients, and a total of 5 extra MMT*s (before and
3, 12, 24 and 60 months after transplantation) for the pancreatic
transplantation recipients. Also, one extra instance of drawing blood is
required (directly after transplantation). The other instances of blood drawing
are timed at the outpatient clinic visits. The risk is considered to be
negligible.