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ENDO: Less Insulin Dependence After TPIAT

<ѻý class="mpt-content-deck">— Islet function preserved with total pancreatectomy with islet auto-transplant (TPIAT)
MedpageToday

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BOSTON -- Patients with severe medically refractory chronic pancreatitis experienced preserved islet function after total pancreatectomy with islet auto-transplant (TPIAT), leading to a lower rate of insulin-dependent diabetes, researchers reported here.

Among 30 patients and 6 months after treatment, an average HbA1c level of 6.8% was achieved, and 71% of patients had levels that were at target, reported , of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues.

Action Points

  • This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The authors also reported at the Endocrine Society annual meeting that patients after initially undergoing off-site islet isolation, during which the pancreas is taken out of the body (procedure done at Massachusetts General Hospital in Boston) before transitioning to on-site autologous islet transplantation.

After 12 months, the average HbA1c levels had risen to 7.5% with 62% of patients on target and 52% of patients requiring no insulin at all, they said. Also, patients reported less pain than presurgery conditions and a better quality of life after returning to work.

"We always tell surgeons, 'Don't throw away those islets!' because we need them," Chaidarun explained. "This can be done at smaller institutions, too, and it's a good option for some patients with intractable chronic pancreatitis."

She added that the mass of the islets in the on-site procedure correlated with favorable outcomes., and since most of the patients still had islet graft function with normal c-peptide levels after the procedure, they started treatment for patients who needed further diabetic control with drugs like metformin and dipeptidyl peptidase-4 inhibitors and not insulin.

The average islet equivalent yields was 4,683 IEq/Kg (range 843-10,214). Ten percent of patients had low yields of <2,500, 57% had moderate yields of 2,500-5,000, and 33% had high yields of >5,000 IEq/Kg, found the authors.

The first off-site procedure -- where the pancreas is completely resected, and the islets are taken and then transplanted back into the patient, usually through the portal vein -- took place in 1977. But the costs of total pancreatectomy with islet auto-transplantation , and the procedure has been neither widespread nor well-studied in the U.S.

"Surgery for chronic pancreatitis has become more and more common, often depriving patients from beta cells with the need to treat them with insulin replacement as we do in individuals with type 1 diabetes," , at the Albert Einstein College of Medicine in New York City, told ѻý.

"The idea of islet auto-transplantation is brilliant and should be done more often," added Zonszein, who was not involved in the study.

The average A1c was 5.7+1.1% with a range of 4.6-8.4%, according to Chaidarun and colleagues. All of the patients had normal stimulated c-peptide levels (3.2+2.1 ng/ml with the normal range being 1.1-4.4 ng/ml); this suggested that most preserved their endogenous insulin production, they wrote.

Presurgery, 11% of the patients already had diabetes requiring treatment with metformin or insulin, 15% had pre-diabetes, and 74% had normal HbA1c levels of less than 5.6%. The mean age of the patients in the study was 43 and 52% were female. The mean weight was 165 lbs (mean body mass index of 26 kg/m2). Patients had pancreatitis for an average of 5 years and most were idiopathic or inherited the disease.

The patients all had diabetes education and underwent lab tests before enrolling, since many effectively went from type 1 diabetes patients to type 2. Chaidarun also shared preliminary data from one patient with a 3-year follow-up since the procedure. That individual was insulin-free within 2 months, does not take diabetes medication, and frequently tests blood glucose levels.

The authors also found that tight glycemic control during the perioperative phase may protect islets and yield better results in the long term.

They concluded that TPIAT should be seen as a viable treatment option for patients with intractable chronic pancreatitis, especially because patients experienced less pain, were able to return to work, and reported a better quality of life.

"Islet auto-transplantation either on-site or off-site islet isolation can be used to avert the burden of complicated and costly diabetic care for carefully selected patients requiring total or sub-total pancreatectomy," they wrote.

"The researchers' experience should motivate large institutions to start such programs in patients undergoing total or sub-total pancreatectomy," Zonszein stated.

Disclosures

Chaidarun disclosed relevant relationships with Novo Nordisk and Dompé.

Primary Source

The Endocrine Society

Chaidarun S, et al "Diabetes management and outcomes of islet auto-transplant after total pancreatectomy: dartmouth experience, using off-site and intra-operative islet isolation" ENDO 2016; OR12-2.