Islet cell transplants may not yet be the holy grail of insulin independence, but they are making substantial gains in resolving severe hypoglycaemia and improving glycaemic variability, an expert says.
Endocrinologist Associate Professor Jane Holmes-Walker was talking to the limbic following the publication of a study comparing the efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycaemia and glycaemic variability in type 1 diabetes (T1D) subjects with severe hypoglycaemia.
The study, published in the journal Transplantation found that after changing from MDI to CSII before transplantation, 10 subjects significantly reduced median HYPO score and hypoglycaemia events, and while HbA1c, mean glucose and median percent time hypoglycaemic on CGM were unchanged with CSII, SD glucose and CONGA4 reduced significantly.
At 12 months post islet transplantation there were significant reductions in all baseline parameters versus CSII.
“In subjects with severe hypoglycaemia suitable for islet transplantation, CSII decreased hypoglycaemia frequency and glycaemic variability compared with MDI whereas islet transplantation resolved hypoglycaemia and further improved glycaemic variability regardless of insulin independence,” the authors concluded.
The first islet cell transplant was undertaken in Australia in 2002, and co-author of the research, Professor Jane Holmes-Walker said the procedure had come a long way since then.
Professor Holmes-Walker, a staff Specialist at Westmead Hospital’s Department of Diabetes and Endocrinology, which is also home to the National Islet Cell Transplant Program described the latest study as “significant”.
She told the limbic the research had shown that islet cell transplantation successfully reduced frequency and severity of hypoglycaemic episodes even with partial graft function and did not depend on achieving insulin independence.
It was also a valuable way to treat severe hypoglycaemia that is asymptomatic, and in patients with impaired hypoglycaemic awareness.
“It seems to be the Holy Grail to be off insulin, but severe hypoglycaemia is what kills and shortens life,” she said. “It’s about improving quality and quantity of life.
The study revealed there was mounting evidence for the effect of glycaemic variability on development of diabetes complications in addition to the effect of elevated HbA1c .
“Therefore, islet transplantation may reduce complications through both improved glycaemic control and reduction in glycaemic variability,” the authors wrote.
Professor Holmes-Walker said six patients per year were receiving islet transplants through the Westmead-based program.
She said there were varying degrees of success when it came to insulin independence – some patients have reached seven years of insulin independence – and a consistent pattern of positive results in addressing hypoglycaemia.
And it also appears that body weight plays a role in determining whether or not a patient will be able to maintain insulin independence.
“Those over 70kg realistically will still need some insulin,” she said.
Related story: Donor shortage changes ICT holy grail
Importantly, she said patients were reporting significant improvements in their quality of life because their hypoglycaemia was under control and glycaemic variability improved.
“I have patients who have never contemplated a trip other than by car to take holidays,” she said. “Once you’ve got stable sugars and no hypoglycaemia you are definitely looking at improved quality of life.
One major issue limiting the widespread appropriateness of islet cell transplant is the need for long-term immunosuppression, and Professor Holmes-Walker said patients must be able to comply with the tablet regime.
Another hurdle is access to the islet cells, which are harvested from a deceased donor and transplanted, within 48 hours. Professor Holmes-Walker said the problem was not having enough donors, but enough of a variety of potential recipients to match them up with.
She said researchers were already looking at developing new immunosuppressants, as well as generating new sources of islets, including the use of stem cells.
Meanwhile, she is happy to see both patients and the endocrinology community showing more interest in the program, and this has translated into her seeing more than double the number of patients this year compared to last.
Patient self-referral is still common, although she is seeing more referral from endocrinologists.
“It’s taken quite a while to get it out to the endocrinology community,” she said. “They’re a bit suspicious of the benefits and what its role is bit there is more data and more awareness and that’s encouraging.”