BTS 2012 Report – Clinical controversy: Islets versus whole pancreas

by Maria Dalby reporting on the presentation by Peter Friend, University of Oxford.  Pancreas transplantation for the treatment of diabetes can be said to be unique amongst transplantations in that there is a genuine medical alternative available to the procedure, namely insulin. Whole pancreas transplantation and islet cell therapy are widely regarded as alternatives, although there are dramatic differences in the level of morbidity and risk involved which continues to cause debate amongst diabetologists and transplant clinicians. Professor Peter Friend, transplant surgeon from Oxford, presented an overview of this controversy and outlined the evidence.

Whole pancreas transplantation is typically performed as a simultaneous pancreas and kidney transplantation (SPK) and involves a large operation with considerable morbidity and appreciable mortality. The clinical outcomes of SPK tend to be good, with 1-year patient survival rates in excess of 95%;¹ data from Professor Friend’s Oxford centre, which employs an alemtuzumab induction protocol, suggests a 5-year survival rate of around 70%. In contrast, islet transplantation is a much less invasive procedure and therefore much safer for the patient. When the so-called ‘Edmonton protocol’ of cell infusions from multiple donors was introduced in 2000, this had a revolutionary effect in that 85% of the patients remained insulin independent at one year post-transplant.² Unfortunately this success rate was not sustained over longer periods, although implementation of alemtuzumab induction has led to an improvement in recent years with 5-year insulin independence rates of around 50%.

The current consensus is to consider pancreas transplantation on two separate indications: firstly, for the treatment of patients with advanced secondary complications of diabetes, the clinical rationale is that large well-controlled studies including the Diabetes Control and Complications (DCCT) study have shown that tight glycaemic control is associated with stabilisation of microvascular complications such as nephropathy and retinopathy,³ and pancreas transplantation provides a means of achieving this level of control successfully. Although the evidence base is not consistent with regards to microvascular outcomes, there is some data to support a histological improvement in nephropathy over a period of 5-10 years after an SPK, and significantly improved 10-year survival rates compared with patients undergoing kidney transplantation alone.⁴ Transplant registry data indicates a significantly greater life expectancy for patients undergoing SPK compared with kidney transplantation alone,⁵ which all in all suggests that whole pancreas transplantation should be the procedure of choice for this patient group.

The other group that may be considered for pancreas transplantation is diabetes patients with intractable metabolic instability – the so-called hypoglycaemia unawareness syndrome, which may be potentially life-threatening and has a detrimental impact on quality of life and ability to work etc. The experience at Oxford has been that these patients may not require full insulin independence to derive significant clinical benefit; islet transplantation may help to reduce the insulin dose and stabilise blood glucose levels, effectively turning ‘difficult’ diabetes patients into ‘regular’ patients. However, Professor Friend cautioned that based on the available evidence, islet transplantation should be used with caution, and only in this patient group, as whole pancreas transplantation is associated with superior function and survival and less risk of sensitisation, albeit with greater overall morbidity.

References:

1. International Pancreas Transplantation Registry. Annual report, 2004.
2. Shapiro AMJ, Lakey JRT, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-238
3. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-986
4. Tydén G, Bolinder J, Solders G, et al. Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation. Transplantation 1999; 67(5): 645-648
5. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant  2004; 4(12): 2018-2026