Journal of Gastrointestinal Surgery

, Volume 23, Issue 5, pp 966–974 | Cite as

Circulating Leptin and Branched Chain Amino Acids—Correlation with Intraductal Papillary Mucinous Neoplasm Dysplastic Grade

  • Michele T. Yip-Schneider
  • Rachel Simpson
  • Rosalie A. Carr
  • Huangbing Wu
  • Hao Fan
  • Ziyue Liu
  • Murray Korc
  • Jianjun ZhangEmail author
  • C. Max SchmidtEmail author
Original Article



The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN.


Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology.


Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed.


Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.


Leptin BCAA IPMN Biomarker Pancreatic cyst 



Intraductal papillary mucinous neoplasm


Branched chain amino acids


Retinol-binding protein-4


Enzyme-linked immunosorbent assay


Pancreatic ductal adenocarcinoma



This study was supported by the National Institutes of Health Grant #1R21CA209366-01, Indiana Clinical and Translational Sciences Institute funded in part by Grant #UL1TR001108 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and National Center for Research Resources Construction Grant #RR020128.

Author Contributions

Yip-Schneider, Zhang, and Schmidt significantly contributed to the conception/design/data interpretation, drafting/revision of the work, as well as approve of the final version and agree to be accountable for all aspects of the work.

Liu and Korc significantly contributed to data interpretation and revision of the work as well as approve of the final version and agree to be accountable for all aspects of the work.

Simpson, Carr, Wu, and Hao significantly contributed to data acquisition/analysis, revision of the work, as well as approval of the final version and agree to be accountable for all aspects of the work.

Compliance with Ethical Standards

All patients and healthy controls provided informed consent in accordance with the Indiana University Institutional Review Board.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© The Society for Surgery of the Alimentary Tract 2018

Authors and Affiliations

  • Michele T. Yip-Schneider
    • 1
    • 2
    • 3
    • 4
  • Rachel Simpson
    • 1
    • 4
  • Rosalie A. Carr
    • 1
    • 4
  • Huangbing Wu
    • 1
    • 4
  • Hao Fan
    • 5
  • Ziyue Liu
    • 6
    • 7
  • Murray Korc
    • 3
    • 8
    • 9
  • Jianjun Zhang
    • 3
    • 5
    Email author
  • C. Max Schmidt
    • 1
    • 2
    • 3
    • 4
    • 8
    Email author
  1. 1.Department of SurgeryIndiana University School of MedicineIndianapolisUSA
  2. 2.Walther Oncology CenterIndianapolisUSA
  3. 3.Indiana University Simon Cancer CenterIndianapolisUSA
  4. 4.Indiana University Health Pancreatic Cyst and Cancer Early Detection CenterIndianapolisUSA
  5. 5.Department of EpidemiologyIndiana University Richard M. Fairbanks School of Public HealthIndianapolisUSA
  6. 6.Department of BiostatisticsIndiana University School of MedicineIndianapolisUSA
  7. 7.Department of BiostatisticsIndiana University Richard M. Fairbanks School of Public HealthIndianapolisUSA
  8. 8.Department of Biochemistry/Molecular BiologyIndiana University School of MedicineIndianapolisUSA
  9. 9.Department of MedicineIndiana University School of MedicineIndianapolisUSA

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