Correspondence

Islet Transplantation as a Treatment for Diabetes

N Engl J Med 2004; 350:2104May 13, 2004

Article

To the Editor:

We respectfully disagree with two points in Robertson's comprehensive review of islet transplantation (Feb. 12 issue)1: the assertions that patients with diabetes and autonomic insufficiency have a “dramatically shortened life span” and that transplantation necessarily reduces the rate of death. In the cited articles and an additional article by Navarro et al.,2 most persons with diabetes had autonomic insufficiency. In fact, autonomic insufficiency lost its statistical significance after adjustment for renal dysfunction and cardiovascular disease in two population-based studies.3,4 When Navarro et al. compared pancreas-transplant recipients with medically treated patients, mortality rates were indistinguishable.2

Robertson states that “when successful, pancreas transplantation is particularly effective,” but we would argue that analyzing mortality rates after successful procedures as compared with unsuccessful procedures introduces bias. Although successful pancreas (or islet) transplantation may improve the quality of life, glycemic control, and other factors, such analyses understate transplantation-related risks. One of us and our colleagues recently reported increased mortality rates during the first four years after transplantation in patients with diabetes and preserved kidney function who were given a pancreas transplant as compared with those who were awaiting a transplant.5

David M. Harlan, M.D.
Kristina I. Rother, M.D.
National Institutes of Health, Bethesda, MD 20892
davidmh@intra.niddk.nih.gov

5 References

1. 1

   Robertson RP. Islet transplantation as a treatment for diabetes -- a work in progress. N Engl J Med 2004;350:694-705
   Full Text | Web of Science | Medline

2. 2

   Navarro X, Kennedy WR, Aeppli D, Sutherland DE. Neuropathy and mortality in diabetes: influence of pancreas transplantation. Muscle Nerve 1996;19:1009-1016
   CrossRef | Web of Science | Medline

3. 3

   Gerritsen J, Dekker JM, TenVoorde BJ, et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. Diabetes Care 2001;24:1793-1798
   CrossRef | Web of Science | Medline

4. 4

   Orchard TJ, Lloyd CE, Maser RE, Kuller LH. Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Res Clin Pract 1996;34:Suppl:S165-S171
   CrossRef | Web of Science | Medline

5. 5

   Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003;290:2817-2823
   CrossRef | Web of Science | Medline

Author/Editor Response

Harlan and Rother disagree that diabetic patients with autonomic insufficiency have an increased mortality rate and that pancreas transplantation reduces this rate. An association between increased mortality and autonomic insufficiency has been documented in scientific publications.1,2 Since patients with autonomic insufficiency usually die from cardiovascular causes, the analytic strategy of eliminating this variable is questionable. That successful pancreas transplantation lessens the mortality rate in this group of patients has been established in a more relevant report by Navarro et al.2 Venstrom and colleagues' assertion that pancreas transplantation leads to an increased mortality rate3 runs the risk of significant bias because the authors made the assumption that patients who remained on a waiting list and those who received a pancreas had a comparable risk of death. Some of the more healthy patients may have decided to continue waiting, and less healthy patients may not have waited. That bias aside, the authors clearly reported no significant increase in mortality in the group of patients who received only a pancreas transplant and a significant improvement in overall survival in the group of patients who received both a pancreas and a kidney.

R. Paul Robertson, M.D.
Pacific Northwest Research Institute, Seattle, WA 98122
rpr@pnri.org

3 References

1. 1

   Ewing DJ, Campbell IW, Clarke BF. Mortality in diabetic autonomic neuropathy. Lancet 1976;1:601-603
   CrossRef | Web of Science | Medline

2. 2

   Navarro X, Kennedy WR, Loewenson RB, Sutherland DER. Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction, and mortality in diabetes mellitus. Diabetes 1990;39:802-806
   CrossRef | Web of Science | Medline

3. 3

   Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003;290:2817-2823
   CrossRef | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Smruti M. Phadnis, Mugdha V. Joglekar, Maithili P. Dalvi, Sudhakar Muthyala, Prabha D. Nair, Surendra M. Ghaskadbi, Ramesh R. Bhonde, Anandwardhan A. Hardikar. (2011) Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo. Cytotherapy 13:3, 279-293
   CrossRef

2. 2

   Mugdha V. Joglekar, Vishal S. Parekh, Sameet Mehta, Ramesh R. Bhonde, Anandwardhan A. Hardikar. (2007) MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3. Developmental Biology 311:2, 603-612
   CrossRef

3. 3

   Sayegh, Mohamed H., Carpenter, Charles B., . (2004) Transplantation 50 Years Later — Progress, Challenges, and Promises. New England Journal of Medicine 351:26, 2761-2766
   Full Text

4. 4

   Jeremy J. Heit, Seung K. Kim. (2004) Embryonic stem cells and islet replacement in diabetes mellitus. Pediatric Diabetes 5:s2, 5-15
   CrossRef