Skip to main content

Advertisement

SpringerLink
Log in

Pancreatic Endocrine Insufficiency

  • Nutrition, Metabolism, and Surgery (Keith Miller, Section Editor)
  • Published:
Current Surgery Reports Aims and scope Submit manuscript

Abstract

Purpose of the Review

This review aims to consolidate the latest knowledge on type 3c diabetes mellitus (T3cDM) and its management and pancreatic endocrine insufficiency (PEI) as a sequela, primarily focusing on two etiologies: pancreatitis and pancreatectomy.

Recent Findings

PEI is a consequence of pancreatogenic diabetes, a distinct type of diabetes mellitus also known as T3cDM. T3cDM develops secondary to diseases of the exocrine pancreas and has a unique pattern of metabolic and hormonal characteristics. Several exocrine pancreatic disorders and procedures including acute, relapsing, and chronic pancreatitis, pancreatic cancer, and pancreatectomy have been identified as underlying causes for the development of T3cDM.

Summary

Diagnosis of T3cDM is challenging as it is often misclassified as type 1 or type 2 DM due to overlapping clinical presentations. Management of T3cDM and the PEI sequela is likewise difficult due to the occurrence of several confounding metabolic dysfunctions and poor nutritional status. Treatment of pancreatic exocrine insufficiency is critical when managing patients with T3cDM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35(Suppl 1):S64–71. https://doi.org/10.2337/dc12-s064. Official subclassification of T3cDM as pancreatogenic diabetes (association of T3cDM with the diseases of the exocrine pancreas)

  2. American DA. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81–90. https://doi.org/10.2337/dc14-S081.

    Article  Google Scholar 

  3. American Diabetes Association Professional Practice C. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S17–38. https://doi.org/10.2337/dc22-S002.

  4. Ewald N, Bretzel RG. Diabetes mellitus secondary to pancreatic diseases (Type 3c)–are we neglecting an important disease? Eur J Intern Med. 2013;24(3):203–6. https://doi.org/10.1016/j.ejim.2012.12.017.

    Article  PubMed  Google Scholar 

  5. Hart PA, Bradley D, Conwell DL, Dungan K, Krishna SG, Wyne K, et al. Diabetes following acute pancreatitis. Lancet Gastroenterol Hepatol. 2021;6(8):668–75. https://doi.org/10.1016/S2468-1253(21)00019-4.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes Metab Res Rev. 2012;28(4):338–42. https://doi.org/10.1002/dmrr.2260.

    Article  CAS  PubMed  Google Scholar 

  7. Valdez-Hernandez P, Perez-Diaz I, Soriano-Rios A, Gomez-Islas V, Garcia-Fong K, Hernandez-Calleros J, et al. Pancreatogenic diabetes, 2 onset forms and lack of metabolic syndrome components differentiate it from type 2 diabetes. Pancreas. 2021;50(10):1376–81. https://doi.org/10.1097/MPA.0000000000001930.

    Article  CAS  PubMed  Google Scholar 

  8. • Narayanan S, Bhutiani N, Adamson DT, Jones CM. Pancreatectomy, islet cell transplantation, and nutrition considerations. Nutr Clin Pract. 2021;36(2):385–97. https://doi.org/10.1002/ncp.10578. Key paper to highlight and consolidate information on perioperative nutritional aspects in patients undergoing total pancreatectomy and islet transplantation.

  9. Conlon KC, Duggan SN. Pancreatogenic type 3c diabetes: underestimated, underappreciated and poorly managed. Practical Gastroenterol. 2017;15

  10. •• Ewald N, Hardt PD. Diagnosis and treatment of diabetes mellitus in chronic pancreatitis. World J Gastroenterol. 2013;19(42):7276–81. https://doi.org/10.3748/wjg.v19.i42.7276. First paper to recommend diagnostic criteria for T3cDM

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gudipaty L, Rickels MR. Pancreatogenic (type 3c) diabetes. Pancreapedia 2015.

  12. Cui Y, Andersen DK. Pancreatogenic diabetes: special considerations for management. Pancreatology. 2011;11(3):279–94. https://doi.org/10.1159/000329188.

    Article  PubMed  Google Scholar 

  13. Sliwinska-Mosson M, Bil-Lula I, Marek G. The cause and effect relationship of diabetes after acute pancreatitis. Biomedicines 2023;11(3):667

  14. Hart PA, Bellin MD, Andersen DK, Bradley D, Cruz-Monserrate Z, Forsmark CE, et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol Hepatol. 2016;1(3):226–37. https://doi.org/10.1016/S2468-1253(16)30106-6.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wynne K, Devereaux B, Dornhorst A. Diabetes of the exocrine pancreas. J Gastroenterol Hepatol. 2019;34(2):346–54. https://doi.org/10.1111/jgh.14451.

    Article  PubMed  Google Scholar 

  16. Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet. 2015;386(9988):85–96. https://doi.org/10.1016/S0140-6736(14)60649-8.

    Article  PubMed  Google Scholar 

  17. Zhi M, Zhu X, Lugea A, Waldron RT, Pandol SJ, Li L. Incidence of new onset diabetes mellitus secondary to acute pancreatitis: a systematic review and meta-analysis. Front Physiol. 2019;10:637. https://doi.org/10.3389/fphys.2019.00637.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cho J, Scragg R, Petrov MS. Risk of mortality and hospitalization after post-pancreatitis diabetes mellitus vs type 2 diabetes mellitus: a population-based matched cohort study. Am J Gastroenterol. 2019;114(5):804–12. https://doi.org/10.14309/ajg.0000000000000225.

    Article  PubMed  Google Scholar 

  19. •• Das SL, Singh PP, Phillips AR, Murphy R, Windsor JA, Petrov MS. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut. 2014;63(5):818–31. https://doi.org/10.1136/gutjnl-2013-305062. Critical work to link AP disease severity to occurrence of DM after AP episodes

    Article  PubMed  Google Scholar 

  20. Shen HN, Yang CC, Chang YH, Lu CL, Li CY. Risk of diabetes mellitus after first-attack acute pancreatitis: a national population-based study. Am J Gastroenterol. 2015;110(12):1698–706. https://doi.org/10.1038/ajg.2015.356.

    Article  PubMed  Google Scholar 

  21. Vipperla K, Papachristou GI, Slivka A, Whitcomb DC, Yadav D. Risk of new-onset diabetes is determined by severity of acute pancreatitis. Pancreas. 2016;45(1):e14–5. https://doi.org/10.1097/MPA.0000000000000536.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Uomo G, Gallucci F, Madrid E, Miraglia S, Manes G, Rabitti PG. Pancreatic functional impairment following acute necrotizing pancreatitis: long-term outcome of a non-surgically treated series. Dig Liver Dis. 2010;42(2):149–52. https://doi.org/10.1016/j.dld.2009.08.007.

    Article  CAS  PubMed  Google Scholar 

  23. Tu J, Zhang J, Ke L, Yang Y, Yang Q, Lu G, et al. Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study. BMC Gastroenterol. 2017;17(1):114. https://doi.org/10.1186/s12876-017-0663-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. • Liu C, Shi Q, Zhang X, Xue E, Li H, Wang W. Incidence and risk factors of fasting hyperglycaemia following first-attack acute pancreatitis before discharge: a retrospective study. BMC Gastroenterol. 2023;23(1):203. https://doi.org/10.1186/s12876-023-02775-7. New paper to evaluate possible risk factors of fasting hyperglycemia following first-attack AP; showed age ≥ 60 years and triglyceride level of ≥ 5.65 mmol/L were independent risk factors

  25. •• O'Brien SJ, Omer E. Chronic pancreatitis and nutrition therapy. Nutr Clin Pract. 2019;34(Suppl 1):S13–S26. https://doi.org/10.1002/ncp.10379. Critical and comprehensive review in managing nutritional dysfunction in CP patients

  26. Hart PA, Kudva YC, Yadav D, Andersen DK, Li Y, Toledo FGS, et al. A reduced pancreatic polypeptide response is associated with new-onset pancreatogenic diabetes versus type 2 diabetes. J Clin Endocrinol Metab. 2023;108(5):e120–8. https://doi.org/10.1210/clinem/dgac670.

    Article  PubMed  Google Scholar 

  27. Sasikala M, Talukdar R, Subramanyam C, Nageshwar RD. The enigma of type 3c diabetes in chronic pancreatitis. Pancreas Open J. 2016;1(2):19–21.

    Article  Google Scholar 

  28. Hardt PD, Krauss A, Bretz L, Porsch-Ozcurumez M, Schnell-Kretschmer H, Maser E, et al. Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus. Acta Diabetol. 2000;37(3):105–10. https://doi.org/10.1007/s005920070011.

    Article  CAS  PubMed  Google Scholar 

  29. •• Makuc J. Management of pancreatogenic diabetes: challenges and solutions. Diabetes Metab Syndr Obes. 2016;9:311–5. https://doi.org/10.2147/DMSO.S99701. Comprehensive summary and evaluation of literature towards the management of T3cDM

  30. Downs EM, Eaton A, Witkowski P, Wijkstrom M, Walsh M, Trikudanathan G, et al. Nutritional risks in patients undergoing total pancreatectomy islet autotransplantation in the POST consortium. J Gastrointest Surg. 2023;27(9):1893–902. https://doi.org/10.1007/s11605-023-05770-1.

    Article  PubMed  Google Scholar 

  31. Witkowski P, Savari O, Matthews JB. Islet autotransplantation and total pancreatectomy. Adv Surg. 2014;48:223–33. https://doi.org/10.1016/j.yasu.2014.05.006.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tian X, Ma Y, Gao H, Zhuang Y, Yang Y. Surgical options for control of abdominal pain in chronic pancreatitis patients. J Pain Res. 2019;12:2331–6. https://doi.org/10.2147/JPR.S208212.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kleeff J, Whitcomb DC, Shimosegawa T, Esposito I, Lerch MM, Gress T, et al. Chronic pancreatitis. Nat Rev Dis Primers. 2017;3:17060. https://doi.org/10.1038/nrdp.2017.60.

    Article  PubMed  Google Scholar 

  34. Wu L, Nahm CB, Jamieson NB, Samra J, Clifton-Bligh R, Mittal A, et al. Risk factors for development of diabetes mellitus (Type 3c) after partial pancreatectomy: a systematic review. Clin Endocrinol (Oxf). 2020;92(5):396–406. https://doi.org/10.1111/cen.14168.

    Article  PubMed  Google Scholar 

  35. Jethwa P, Sodergren M, Lala A, Webber J, Buckels JA, Bramhall SR, et al. Diabetic control after total pancreatectomy. Dig Liver Dis. 2006;38(6):415–9. https://doi.org/10.1016/j.dld.2006.01.022.

    Article  CAS  PubMed  Google Scholar 

  36. Andersen DK. Management of endocrine failure in chronic pancreatitis. Pancreapedia. 2016. https://doi.org/10.3998/panc.2016.6.

  37. •• Sutherland DE, Radosevich DM, Bellin MD, Hering BJ, Beilman GJ, Dunn TB, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg. 2012;214(4):409–24; discussion 24–6. https://doi.org/10.1016/j.jamcollsurg.2011.12.040. Seminal paper on the outcomes of TPIAT

  38. • Rickels MR, Robertson RP. Pancreatic Islet transplantation in humans: recent progress and future directions. Endocr Rev. 2019;40(2):631–68. https://doi.org/10.1210/er.2018-00154. Important review on human islet transplantation

    Article  PubMed  Google Scholar 

  39. Johnston PC, Lin YK, Walsh RM, Bottino R, Stevens TK, Trucco M, et al. Factors associated with islet yield and insulin independence after total pancreatectomy and islet cell autotransplantation in patients with chronic pancreatitis utilizing off-site islet isolation: Cleveland Clinic experience. J Clin Endocrinol Metab. 2015;100(5):1765–70. https://doi.org/10.1210/jc.2014-4298.

    Article  CAS  PubMed  Google Scholar 

  40. Narayanan S, Loganathan G, Dhanasekaran M, Tucker W, Patel A, Subhashree V, et al. Intra-islet endothelial cell and beta-cell crosstalk: implication for islet cell transplantation. World J Transpl. 2017;7(2):117–28. https://doi.org/10.5500/wjt.v7.i2.117.

    Article  Google Scholar 

  41. Dominguez-Munoz JE, Phillips M. Nutritional therapy in chronic pancreatitis. Gastroenterol Clin North Am. 2018;47(1):95–106. https://doi.org/10.1016/j.gtc.2017.09.004.

    Article  PubMed  Google Scholar 

  42. •• Chinnakotla S, Bellin MD, Schwarzenberg SJ, Radosevich DM, Cook M, Dunn TB, et al. Total pancreatectomy and islet autotransplantation in children for chronic pancreatitis: indication, surgical techniques, postoperative management, and long-term outcomes. Ann Surg. 2014;260(1):56–64. https://doi.org/10.1097/SLA.0000000000000569. Seminal paper on outcomes of pediatric TPIAT

    Article  PubMed  Google Scholar 

  43. • Swauger SE, Hornung LN, Elder DA, Balamurugan AN, Vitale DS, Lin TK, et al. Predictors of glycemic outcomes at 1 year following pediatric total pancreatectomy with islet autotransplantation. Diabetes Care. 2022;45(2):295–302. https://doi.org/10.2337/dc21-1222. Novel article on glucose management in the immediate and early (1year) phase post TPIAT in children

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tellez SE, Hornung LN, Courter JD, Abu-El-Haija M, Nathan JD, Lawson SA, et al. Improved Glycemic outcomes with early initiation of insulin pump therapy in pediatric postoperative total pancreatectomy with islet autotransplantation. J Clin Med. 2021. https://doi.org/10.3390/jcm10112242.

  45. • Tellez S, Hornung L, Abu-El-Haija M, Elder D. Metabolic outcomes in pediatric patients one-year post-total pancreatectomy with islet autotransplantation after early pump initiation. J Clin Med. 2023. https://doi.org/10.3390/jcm12093319. Novel article on glucose management in the immediate and early (1year) phase post TPIAT in children

  46. Tellez SE, Hornung LN, Vitale DS, Lawson SA, Abu-El-Haija MA, Elder DA. Endocrine management and clinical outcomes in a cohort of pediatric patients undergoing total pancreatectomy with Islet autotransplantation. Diabetes Technol Ther. 2023;25(11):800–7. https://doi.org/10.1089/dia.2023.0243.

    Article  PubMed  Google Scholar 

Download references

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Department of Pediatric Surgery, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA

    Siddharth Narayanan & Colton D. Wayne

  2. Center for Perinatal Research, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Siddharth Narayanan & Colton D. Wayne

  3. Department of Surgery, Baylor University Medical Center, 3600 Gaston Ave, Dallas, TX, 75246, USA

    Colton D. Wayne

  4. Wisconsin Institute for Discovery, University of Wisconsin-Madison, 330 N Orchard St, Madison, WI, 53715, USA

    Jayaraman Tharmalingam

  5. Division of Transplantation, University of Louisville, 550 South Jackson Street, Louisville, KY, 40202, USA

    Yaser Al-Salmay

  6. Hiram C. Polk Jr. MD Department of Surgery, Division of Transplantation, University of Louisville, 550 South Jackson Street, Louisville, KY, 40202, USA

    Christopher M. Jones

Authors
  1. Siddharth Narayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Colton D. Wayne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jayaraman Tharmalingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yaser Al-Salmay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SN analyzed the literature, collected the data, and wrote the initial draft of the manuscript. CW and JT helped in collecting the data and edited the manuscript. YAS and CMJ provided framework for the study, reviewed, and edited the manuscript. All authors read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Christopher M. Jones.

Ethics declarations

Conflict of interest

All authors have nothing to disclose.

Human and Animal Rights and Informed Consent

No animal or human subjects by the authors were used in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Narayanan, S., Wayne, C.D., Tharmalingam, J. et al. Pancreatic Endocrine Insufficiency. Curr Surg Rep 12, 52–57 (2024). https://doi.org/10.1007/s40137-024-00389-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40137-024-00389-w

Keywords

Search

Navigation