medwireNews: The first randomized trial of islet transplantation supports its use in patients with severe, unstable type 1 diabetes.
The TRIMECO trial is published in The Lancet Diabetes & Endocrinology, in which Shareen Forbes (University of Edinburgh, UK) and co-authors of a linked commentary describe it as “a landmark achievement by a major European trial group, providing robust evidence to guide clinical decision making in this field.”
They believe the results “clearly” demonstrate the worth of islet transplantation in patients for whom intensive insulin treatment has failed. “It is now time to integrate islet transplantation into the stepped care of these patients,” they say.
For the study, Sandrine Lablanche (Grenoble Alpes University, France) and co-researchers recruited 47 patients aged an average of 51 years who were eligible for islet transplantation because they had at least two severe hypoglycemic events per year (77%), hypoglycemia unawareness (4%), or poor glycemic control following a kidney transplant (19%).
The patients had these difficulties despite a multidisciplinary approach to helping them gain control of their blood glucose.
Twenty-six patients were randomly assigned to immediate inclusion on the islet transplantation waiting list. During the first 6 months after receiving their first infusion of islet cells, 64% of these patients attained a modified β-score of 6 or higher, indicating a successful transplant.
The β-score accounts for fasting glucose, C-peptide, and antidiabetic medication use. Undetectable C-peptide requires a score of 0, however, so the researchers modified the score to allow its use in the study control group.
The 21 patients in this group were encouraged to adopt insulin pump therapy if they were not already on it (64% were) and remained on insulin therapy for 6 months, after which they were added to the islet transplantation waiting list. During this 6-month period, none of them attained a β-score of 6 or more. Their median score increased from 0 to 1.5, but that in the transplantation group rose from 0 to 6.
Average glycated hemoglobin levels after 6 months were 5.6% in the transplantation group versus 8.2% in the control group and 84% versus 0% of patients had a level below 7.0% without severe hypoglycemia. Those who underwent transplantation had a median of zero severe hypoglycemic events per year, compared with two in the control group.
In all, 44% of patients in the immediate transplantation group were able to stop using insulin within 6 months of first infusion. And 59% of all 46 patients who underwent islet transplantation during the study, whether immediate or delayed, achieved independence from insulin within 12 months of their first infusion. One patient in the waiting-list group died before first infusion, because of prolonged nocturnal hypoglycemia.
The most frequent adverse events included infections, gastrointestinal disorders, and cytopenia. In addition, 6% of transfusions in 13% of patients were complicated by bleeding, which the commentators say is “was surprising given that the included centres were highly experienced in islet transplantation, highlighting a need to optimise percutaneous hepatic procedures to prevent this avoidable complication.”
All patients had a reduction in estimated glomerular filtration rate during the 12 months after first infusion, from a median of 90.5 to 71.8 mL/min per 1.73 m2 in those who had not undergone kidney transplantation and from 63.0 to 57.0 mL/min in those who had. The researchers attribute this to “calcineurin inhibitor therapy and reduction of hyperfiltration driven by the improvement in glycaemic control.”
They conclude: “A careful analysis of renal function is required before islet transplantation, and candidates should be informed of the risks of islet transplantation before undergoing the procedure.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group
See also:
Promising alternative to hepatic islet transplantation reported