Long-Term Islet Graft Functional Assessment in More than 500 Patients Undergoing Total Pancreatectomy with...

Total pancreatectomy and intraportal islet cell autotransplantation (TPIAT) is increasingly being offered to patients with refractory chronic pancreatitis. Understanding factors that affect islet function over time is critical.

We evaluated factors associated with islet function during 12 years post-TPIAT using mixed meal tolerance testing. Insulin independence and HbA1c were assessed at each time. We compared area under the curve (AUC) C-peptide, AUC glucose, insulin-independent, and hemoglobin A1c patterns over time by patient characteristics using generalized linear mixed models.

A total of 555 patients (median age 32 [interquartile range 17 to 45] years, 25% pediatric; 70% women, 41% overweight or obese) undergoing TPIAT were studied. A median islet equivalents per kg (IEQ/kg) transplanted was 3,696 (interquartile range 2,449 to 5,494) with 26% receiving low (less than 2,500 IEQ/kg), 43% moderate (2,500 to 5,000 IEQ/kg), and 31% high islet mass (more than 5,000 IEQ/kg). AUC C-peptide immediately post-TPIAT was lowest in those with low islet mass and remained low over time. AUC C-peptide showed a modest increase in islet function more than 3 to 4 years in moderate or high islet mass, followed by decline (p < 0.0001 for difference in post-TPIAT trajectory by group). Children have better long-term islet function, particularly beyond 5 years post-TPIAT, although the difference did not reach statistical significance (p = 0.0608); and overweight individuals have declining islet function long term, whereas those with normal or low BMI have gains in the first 3 to 5 years (p < 0.0001). Mean hemoglobin A1c was sustained at <7% for 8 years in high islet mass.

In patients with high islet mass transplanted, islet function improves in the first several years after islet autotransplantation. Islet function is sustained longer in children than in adults. Overweight or obese body habitus may be detrimental to long-term islet function, highlighting the importance of maintaining a healthy body weight for TPIAT recipients.