Total pancreatectomy and intraportal islet cell auto transplantation (TPIAT) is increasingly being offered to patients with refractory chronic pancreatitis. Understanding factors that impact islet function over time is critical. We evaluated factors associated with islet function over 12 years post TPIAT using mixed meal tolerance testing (MMTT). Insulin independence and HbA1c were assessed at each time. We compared AUC C-peptide, AUC glucose, insulin independent and HbA1c patterns over time by patient characteristics using generalized linear mixed models. 555 patients (median age 32 (IQR 17,45) years, 25% pediatric; 70% female, 41% overweight/obese) undergoing TPIAT were studied. Median islet equivalents/kg (IEQ/kg) transplanted was 3,696 (IQR 2,449, 5,494) with 26% receiving low (<2500 IEQ/kg), 43% moderate (2500-5000 IEQ/kg), and 31% high islet mass (>5000 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 over 3-4 years in moderate/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 while those with normal/low BMI have gains in the first 3-5 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 IAT. Islet function is sustained longer in children than in adults. Overweight/obese body habitus may be detrimental to long-term islet function, highlighting the importance of maintaining a healthy body weight for TPIAT recipients.
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