Effect of intrapancreatic fat on diabetes outcomes after total pancreatectomy with islet autotransplantation

Muhammed Kizilgul, Joshua J. Wilhelm, Gregory J. Beilman, Srinath Chinnakotla, Ty B. Dunn, Timothy L. Pruett, Muhamad Abdulla, David Heller, Martin L. Freeman, Sarah J. Schwarzenberg, Bernhard J. Hering, Melena D. Bellin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)286-295
Number of pages10
JournalJournal of Diabetes
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2018

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Pancreatectomy
Autologous Transplantation
Fats
Insulin
Histology
Glucose
Chronic Pancreatitis
Meals
Adipose Tissue
Fatty Acids

Keywords

  • diabetes
  • intrapancreatic fat
  • total pancreatectomy with islet autotransplantation
  • β-cell function

PubMed: MeSH publication types

  • Journal Article

Cite this

Effect of intrapancreatic fat on diabetes outcomes after total pancreatectomy with islet autotransplantation. / Kizilgul, Muhammed; Wilhelm, Joshua J.; Beilman, Gregory J.; Chinnakotla, Srinath; Dunn, Ty B.; Pruett, Timothy L.; Abdulla, Muhamad; Heller, David; Freeman, Martin L.; Schwarzenberg, Sarah J.; Hering, Bernhard J.; Bellin, Melena D.

In: Journal of Diabetes, Vol. 10, No. 4, 01.04.2018, p. 286-295.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Beilman, Gregory J.

AU - Chinnakotla, Srinath

AU - Dunn, Ty B.

AU - Pruett, Timothy L.

AU - Abdulla, Muhamad

AU - Heller, David

AU - Freeman, Martin L.

AU - Schwarzenberg, Sarah J.

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AU - Bellin, Melena D.

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AB - 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.

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