Background: Pancreatic fat may adversely affect β-cell mass and function, possibly via local release of non-esterified fatty acids, and proinflammatory and vasoactive factors released by adipose tissue. However, the effects of intrapancreatic fat in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation (TPIAT) have not been studied. This study investigated whether pancreatic fatty infiltration has a negative effect on metabolic outcomes following TPIAT. Methods: The association between pancreatic fatty infiltration and diabetes outcomes was studied in 79 patients with low or high pancreatic fat content (LPF [n = 53] and HPF [n = 26], respectively) undergoing TPIAT. Pancreatic fatty infiltration was stratified using gross examinations during isolation and validated with histomorphometry of archived histology samples. Results: Fat area percentage in histology samples differed significantly between the LPF and HPF groups (2.1% ± 4.3% vs 10.6% ± 8.9%, respectively; P = 0.0009). Insulin dependence was more common in the HPF group, whereas more patients in the LPF group were insulin independent or on partial insulin supplementation at 1 year (P = 0.022). Furthermore, 1- and 2-h glucose concentrations during mixed-meal tolerance tests were significantly higher in the HPF group (P = 0.032 and 0.027, respectively) and β-scores (a composite measure of islet function and metabolic control) were significantly greater in the LPF than HPF group (6.1 ± 1.7 vs 4.6 ± 2.0; P = 0.034). Conclusions: Patients with HPF were more likely to be insulin dependent, with higher postprandial glucose excursion, suggesting that intrapancreatic fat may lead to β-cell dysfunction with detrimental effects on diabetes outcomes after TPIAT.
Bibliographical noteFunding Information:
The authors are incredibly grateful to the islet manufacturing and clinical care teams, who are instrumental to the success of the TPIAT program at the University of Minnesota. Special thanks go to Tom Gilmore, Zach Swanson, Jacob Ricks, Louise Berry, and Marie Cook. Muhammed Kizilgul was supported by a grant from The Scientific and Technical Research Council of Turkey (TUBITAK).
© 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd
- intrapancreatic fat
- total pancreatectomy with islet autotransplantation
- β-cell function