Medical Policy: 07.03.01 
Original Effective Date: October 2004 
Reviewed: November 2015 
Revised: December 2014 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.


One of the major functions of the pancreas is the production of two hormones, insulin and glucagon. The production of these hormones take place in endocrine cell clusters located on the pancreas called the islet of Langerhans. The islet of Langerhans make up approximately 1 percent to 2 percent of the total pancreas.    


There are approximately one million islets in a healthy adult. Most islet cells are concentrated towards the tail end of the pancreas. Islets are composed of two types of cells:

  • Alpha Cells: which produce glucagon, a hormone that raises the level of glucose (sugar) in the blood.
  • Beta Cells: which produce insulin, a hormone that reduces the level of glucose (sugar) in the blood by helping the body use glucose for energy.

Islet cell transplant tissue comes either from the patient (autologous transplant) or from a cadaveric donor (allogeneic transplant).  Currently, only individuals with either chronic pancreatitis or type 1 diabetes mellitus have been subject to clinical investigations.


Chronic Pancreatitis
Chronic pancreatitis is inflammation of the pancreas that does not heal or improve, it gets worse over time and leads to permanent damage. Chronic pancreatitis eventually impairs an individual’s ability to digest food and make pancreatic hormones. Individuals with chronic pancreatitis can experience intractable pain that can only be relieved with a total or near total pancreatectomy. However, the pain relief must be balanced against the certainty that the individual will be rendered an insulin-dependent diabetic.


Autologous islet cell transplantation has been investigated as a technique to prevent this serious morbidity of surgically induced diabetes due to the removal of the individual’s pancreas. The transplant is generally performed during the pancreatectomy procedure,  islet cells are isolated from the resected pancreas using enzymes, and a suspension of the cells is injected into the portal vein of the patient’s liver. Once implanted, the beta cells in these islets begin to make and release insulin. Because the body recognizes these islet cells as its own, there is no rejection of these cells by the patient’s body.


Although the published literature regarding autologous islet cell transplant is limited, the procedure appears to significantly decrease the occurrence of surgically induced diabetes after total or near total pancreatectomy in patients with chronic pancreatitis. Also, this procedure is not associated with serious complications or morbidity. The evidence is insufficient to demonstrate the efficacy of autologous islet cell transplantation performed for any other indication.


Type 1 Diabetes Mellitus
Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Islet cell autoantibodies (ICAs) are theorized to cause the individual to reject their own islet cells, leading to insulin deficiency. Individuals with type 1 diabetes do not have viable beta cells and therefore, cannot receive an autologous islet cell transplant.


Allogeneic islet cell transplant has been proposed as a treatment for patients with type 1 diabetes to restore normoglycemia (normal glucose levels) and to reduce or eliminate the long-term complications of diabetes such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. Islet cell transplantation potentially offers an alternative to whole-organ pancreas transplantation.


Allogeneic islet cell transplant is a procedure in which islets are obtained from deceased organ donor and are purified, processed and transferred into the transplant patient. A limitation of allogeneic islet cell transplantation is that 2 or more donor organs are usually required for successful transplantation. A pancreas that is rejected for whole-organ transplant is typically used for islet transplantation. Transplant patients typically receive two infusions with an average of 400,000 to 500,000 islets per infusion. Once implanted in the liver, the beta cells in these islets begin to make and release insulin. The patient will be started on immuosuppressive therapy to prevent allograft rejection. 


The techniques for allogeneic islet cell transplants are evolving, and the impact on the net health outcome is still uncertain. Longer follow up is needed to evaluate the long-term safety of allogeneic islet cell transplantation and its impact on complications of diabetes mellitus.  


Regulatory Status
Allogeneic islet cells are subject to regulation by the U.S. Food and Drug Administration (FDA), which classifies allogeneic islet cells transplantation as somatic cell therapy; therefore, allogeneic islet cells require pre-market approval. Additionally, allogeneic islet transplantation must be conducted under FDA investigational new drug (IND) regulations.

Prior Approval:


Not applicable


See also Medical Policy 07.03.09 Pancreas Transplants (including simultaneous pancreas-kidney), pancreas alone, and pancreas after kidney)
See also Medical Policy 01.01.26 Artificial Pancreas Device System


Autologous Pancreas Islet Cell Transplantation
Autologous pancreas islet cell transplantation may be considered medically necessary as an adjunct to a total or near-total pancreatectomy in patients with chronic pancreatitis.


Autologous pancreas islet cell transplantation is considered investigational when the above criteria is not met and for all other indications because the safety and/or effectiveness of this procedure for all other indications can not be established based on available peer reviewed literature. 


Allogeneic Pancreas Islet Cell Transplantation
Allogeneic pancreas islet cell transplantation is considered investigational for all indications including the treatment of type 1 diabetes.


The techniques for allogeneic islet cell transplants are evolving; the impact on net health outcomes is still uncertain. Longer follow up with larger numbers of patients is needed before conclusions can be drawn about the safety of allogeneic islet transplantation and its impact on complications of diabetes mellitus, thus the procedure is considered investigational

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 48160 Pancreatectomy, total or subtotal, with autologous transplantation of pancreas or pancreatic islet cells.
  • 48999 Unlisted procedure, pancreas (when specified as pancreatic islet cell transplantation)
  • G0341 Percutaneous islet cell transplant, includes portal vein catheterization and infu
  • G0342 Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion
  • G0343 Laparotomy for islet cell transplant, includes portal vein catheterization and infusion
  • S2102 Islet cell tissue transplant from pancreas; allogeneic  

Selected References:

  • Piper MA, Seidenfeld J, Aronson N. Islet Transplantation in Type 1 Diabetes Mellitus. Evidence Report/Technology Assessment No. 98 (Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center). AHRQ Publication No. 04-E017-2. Rockville, MD: Agency for Healthcare Research and Quality. April 2004.
  • Wahoff DC, Papalois BE, Najarian JS, et al. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222(4):562-79.
  • Robertson RP, Lanz KJ, Sutherland DE, et al. Prevention of diabetes for up to 13 years by auto islet transplantation after pancreatectomy for chronic pancreatitis. Diabetes 2001; 50(1):47-50.
  • TARGET [database online]. Plymouth Meeting (PA): ECRI; 2005 March. Islet cell transplantation for type 1 diabetes.
  • Frank A, Deng S, Huang X et al. Transplantation for type 1 diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 2004 Oct; 240(4):631-40.
  • Robertson RP. Islet transplantation as a treatment for diabetes-a work in progress. NEJM. 2004; 350(7):694-705.
  • TARGET [database online]. Plymouth Meeting (PA): ECRI; 2005 March. (Updated 2005 June 27) Islet cell transplantation for type 1 diabetes.
  • Frank A, Deng S, Huang X et al. Transplantation for type 1 diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 2004 Oct; 240(4):631-40.
  • Robertson RP. Islet transplantation as a treatment for diabetes-a work in progress. NEJM. 2004; 350(7):694-705.
  • ECRI. Islet cell transplantation for the treatment of Type 1 diabetes. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Service; 2005 Oct. 80 p. (Windows on medical technology; no. 130).
  • Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE, American Diabetes Association.  Position statements: Pancreas and islet transplantation in type 1 diabetes. Diabetes Care. 2006 Apr;29(4):935.
  • National Institutes of Health (US). Collaborative Islet Transplant Registry: Annual Report. Bethesda, MD: National Institute of Diabetes and Digestive Kidney DiseasesExternal Site September 2008. Accessed March 16, 2009.
  • Jindal RM, Ricordi C, Shriver CD. Autologous pancreatic islet transplantation for severe trauma. N Engl J Med. 2010 Apr 22;362(16):1550.
  • Halban PA, German MS Kahn SE et al. Current status of islet cell replacement and regeneration therapy. J Clin Endocrinol Metab. 2010 Mar;95(3):1034-43. Epub 2010 Jan 8.
  • Gremizzi C, Vergani A, Paloschi V et al. Impact of pancreas transplantation of type 1 diabetes-related complications. Curr Opin Organ Transplant. 2010 Feb; 15(1):119-23.
  • Thompson DM, Meloche M, Ao Z et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011 Feb 15;91(3):373-8.
  • Posselt AM, Szot GL, Frassetto LA et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on R-cell adhesion or costimulation blockade. Transplantation. 2010 Dec 27;90(12):1595-601.
  • Posselt AM, Bellin MD, Tavakol M et al. Islet transplantation in type 1 diabetes using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant. 2010 Aug;10(8):1870-80.
  • Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010 Mar;6(3):139-48.
  • de Vos P, Spasojevic M, Faas MM. Treatment of diabetes with encapsulated islets. Adv Exp Med Biol. 2010; 670:38-53.
  • Bramis K, Gordon-Weeks AN, Friend PJ et al. Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Br J Surg. 2012 Jun;99(6):761-6. doi: 10.1002/bjs.8713. Epub 2012 Mar 20.
  • Dong M, Parsaik AK, Erwin PJ et al. Systematic review and meta-analysis: islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol (Oxf). 2011 Dec;75(6):771-9. doi: 10.1111/j.1365-2265.2011.04121.x.
  • Sutherland DE, Radosevich DM, Bellin MD et al. Total pancreatectomy and islet transplantation for chronic pancreatitis. J AM Coll Surg. 2012 Apr;214(4):409-24. Epub 2012 Mar 6.
  • Desai CS, Stephenson DA, Khan KM et al. Novel techniques of total pancreatectomy before autologous islet transplants in chronic pancreatitis patients. J AM Coll Surg. 2011 Dec;213(6):e29-34. Epub 2011 Oct 13.
  • Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J. 2011 Jun;35(3):199-206. Epub 2011 Jun 30.
  • Jamiolkowski RM, Guo LY, Li YR et al. Islet transplantation in type 1 diabetes mellitus. Yale J Biol Med. 2012 Mar;85(1):37-43. Epub 2012 Mar 29.
  • ECRI Hotline response: Indications and contraindications for Islet Cell Transplantation for Treating Type 1 Diabetes ECRI Institute 2012 Nov.
  • National Institute for Health and Clinical ExcellenceExternal Site (NICE). Autologous Pancreatic Islet Cell Transplantation for Improved Glycaemic Control after Pancreatectomy. September 2008.
  • National Institute for Health and Clinical ExcellenceExternal Site (NICE). Allogeneic Pancreatic Islet Cell Transplantation for Type 1 Diabetes Mellitus. April 2008.
  • National Diabetes Information ClearinghouseExternal Site (NDIC). Pancreatic Islet Transplantation.
  • UNOS Pancreas Allocation Policy. September 1, 2013.
  • CMSExternal Site National Coverage Determination for Pancreas Transplants (260.3).
  • UpToDateExternal Site Pancreas and Islet Transplantation in Diabetes Mellitus. R. Paul Robertson, M.D.. Topic last updated April 30, 2013.
  • UpToDateExternal Site Treatment of Chronic Pancreatitis. Steven D. Freedman, M.D., PhD. Topic last updated October 8, 2013.
  • American Diabetes AssociationExternal Site Islet Transplantation.
  • ECRIExternal Site Hotline Response: Islet Cell Transplantation for Treating Type 1 Diabetes. Updated May 27, 2015.
  • MedscapeExternal Site Type 1 Diabetes Mellitus, updated October 21, 2014. 
  • National Institute for Health and Clinical ExcellenceExternal Site (NICE). Type 1 Diabetes in Adults: Diagnosis and Management (NG17), August 2015.
  • Al-Adra. Gill RS, et. al. Single Donor Islet Transplantation and Long Term Insulin Dependence in Select Patients with Type 1 Diabetes Mellitus. Transplantation 2014 Nov 15:98(9):1007-12
  • Anazawa T, Saito T, et. al. Long Term Outcomes of Clinical Transplantation of Pancreatic Islets with Uncontrolled Donors after Cardiac Death: A Multicenter Experience in Japan. Transplant Proc. 2014 Jul-Aug:46(6):1980-4
  • Brooks AM, Oram R, et. al. Demonstration of an Intrinsic Relationship Between Endogenous C-Peptide Concentration and Determinats of Glycemic Control in Type 1 Diabetes Following Islet Transplantation. Diabetes Care 2015 Jan;38(1):105-12
  • Byrne ML, Hopkins D, et. al. Outcomes for Adults with Type 1 Diabetes Referred with Severe Hypoglycaemia and/or Referred for Islet Transplantation to a Specialist Hypoclycaemia Service. Horm Metab Res 2015 Jan;47(1):9-15
  • Caiazzo R, Vantyghem MC, et. al. Impact of Procedure-Related Complications on Long-Term Islet Transplantation Outcome. Transplantation 2015 May:99(5):979-84
  • Colling KP, Blondet JJ, et. al. Positive Sterility Cultures of Transplant Solutions During Pancreatic Islet Autotransplantation are Associated Infrequently with Clinical Infection. Surg Infect (Larchmt). 2015 Apr;16(2):115-23
  • Georgiey G, Beltran Del Rio M, et. al. Patient Quality of Life and Pain Improve after Autologous Islet Transplantation (AIT) for Treatment of Chronic Pancreatitis: 53 Patient Series at the University of Arizona. Pancreatology 2015 Jan-Feb;15(1):40-5
  • Qi M, Kinzer K, et. al. Five Year Follow-Up of Patients with Type 1 Diabetes Transplanted with Allogeneic Islets: The UIC Experience. Acta Diabetol. 2014 Oct;51(5):833-43
  • Tai Ds, Shen N, et. al. Autologous Islet Transplantation with Remote Islet Isolation after Pancreas Resection for Chronic Pancreatitis. Jama Surg 2015 Feb;150(2):118-24
  • Thakor AS, Sangha BS. et. al. Percutaneous Autologous Pancreatic Islet Cell Transplantation for Traumatic Pancreatic Injury. J Clin Endocrinol Metab 2015 Apr;100(4):1230-3

Policy History:

  • November 2015 - Annual Review, Policy Renewed
  • December 2014 - Annual Review, Policy Revised
  • February 2014 - Annual Review, Policy Revised
  • March 2013 - Annual Review, Policy Renewed
  • July 2012 - Annual Review, Policy Renewed
  • August 2011 - Annual Review, Policy Renewed

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.