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Horm Metab Res 2015; 47(01): 4-8
DOI: 10.1055/s-0034-1385876
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Islet Transplantation at the Dresden Diabetes Center: Five Years’ Experience

B. Ludwig
1   Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany
2   Centre for Diabetes Research, Paul Langerhans Institute Dresden, Dresden, Germany
,
A. Reichel
1   Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany
,
A. Kruppa
1   Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany
,
S. Ludwig
2   Centre for Diabetes Research, Paul Langerhans Institute Dresden, Dresden, Germany
3   Department of Visceral, Thorax, and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
,
A. Steffen
1   Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany
2   Centre for Diabetes Research, Paul Langerhans Institute Dresden, Dresden, Germany
,
J. Weitz
3   Department of Visceral, Thorax, and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany
,
S. R. Bornstein
1   Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany
2   Centre for Diabetes Research, Paul Langerhans Institute Dresden, Dresden, Germany
4   Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany
5   Department of Endocrinology and Diabetes, King’s College, London, England
› Author Affiliations
Further Information

Publication History

received 07 July 2014

accepted 15 July 2014

Publication Date:
01 August 2014 (online)

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Abstract

For the majority of patients with type 1 diabetes intensive insulin therapy is effective and safe for maintaining glycemia and minimizing diabetes-associated complications. However, a rare number of patients show highly labile metabolic control and experience repeated and unpredictable hypoglycemic episodes. Such condition is often caused by defective counterregulatory mechanisms and autonomous neuropathy. Patients are at high risk for severe acute and chronic complications, and quality of life is considerably impaired. For this small subset of patients, restoration of endogenous insulin secretion can substantially improve metabolic control and quality of life. In our experience, this is irrespective of insulin independency. Here, we report on our 5 years’ experience with implementing islet transplantation as a potential treatment option for type 1 diabetes. All patients were treated by long-term insulin pump therapy prior to enrolment. The main indication was severely unstable diabetes and repeated hypoglycemia. From 2008 to 2013, 10 patients have been transplanted with single islet infusion; mean follow-up time was 35 months. All patients show persistent graft function, stable glycemic control with a reduction in HbA1c in the absence of hypoglycemia. All patients are kept on minimal exogenous insulin. In conclusion, islet transplantation can be an excellent therapy for selected patients. Key prerequisite for success is a strict indication. The primary goal for islet transplantation should be stabile glycemia and prevention of hypoglycemia rather than insulin independence. In fact, maintaining minimal exogenous insulin may protect the islet graft from metabolic stress and even prolong islet graft function.

Key words

diabetes mellitus - hypoglycemia - unawareness - insulin deficiency
 

  • References

  • 1 Standards of medical care in diabetes 2014. Diabetes Care 2014; 37 (Suppl. 01) S14-S80
    CrossrefPubMedGoogle Scholar
  • 2 Jacqueminet S, Masseboeuf N, Rolland M, Grimaldi A, Sachon C. Limitations of the so-called “intensified” insulin therapy in type 1 diabetes mellitus. Diabetes Metab 2005; 31 (4 Pt 2) 4s45-4s50
    PubMedGoogle Scholar
  • 3 Reichel A, Rietzsch H, Ludwig B, Rothig K, Moritz A, Bornstein SR. Self-adjustment of insulin dose using graphically depicted self-monitoring of blood glucose measurements in patients with type 1 diabetes mellitus. J Diabetes Sci Technol 2013; 7: 156-162
    PubMedGoogle Scholar
  • 4 2007 Update on allogeneic islet transplantation from the Collaborative Islet Transplant Registry (CITR). Cell Transplant 2009; 18: 753-767
    CrossrefPubMedGoogle Scholar
  • 5 Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, Oberholzer J, Odorico JS, Garfinkel MR, Levy M, Pattou F, Berney T, Secchi A, Messinger S, Senior PA, Maffi P, Posselt A, Stock PG, Kaufman DB, Luo X, Kandeel F, Cagliero E, Turgeon NA, Witkowski P, Naji A, O’Connell PJ, Greenbaum C, Kudva YC, Brayman KL, Aull MJ, Larsen C, Kay TW, Fernandez LA, Vantyghem MC, Bellin M, Shapiro AM. Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 2012; 35: 1436-1445
    CrossrefPubMedGoogle Scholar
  • 6 Ricordi C, Gray DW, Hering BJ, Kaufman DB, Warnock GL, Kneteman NM, Lake SP, London NJ, Socci C, Alejandro R, Zeng Y, Scharp DW, Viviani G, Falqui L, Tzakis A, Bretzel RG, Federlin K, Pozza G, James RFL, Rajotte RV, Di Carlo V, Morris PJ, Sutherland DER, Starzl TE, Mintz DH, Lacy PE. Islet isolation assessment in man and large animals. Acta Diabetol Lat 1990; 27: 185-195
    CrossrefPubMedGoogle Scholar
  • 7 Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54: 2060-2069
    CrossrefPubMedGoogle Scholar
  • 8 Miller RG, Secrest AM, Sharma RK, Songer TJ, Orchard TJ. Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort. Diabetes 2012; 61: 2987-2992
    CrossrefPubMedGoogle Scholar
  • 9 Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003; 26: 832-836
    CrossrefPubMedGoogle Scholar
  • 10 Federlin K, Pozza G. Indications for clinical islet transplantation today and in the forseeable future – the diabetologist’s point of view. J Mol Med (Berl) 1999; 77: 148-152
    CrossrefPubMedGoogle Scholar
  • 11 Bouwens L. Beta cell regeneration. Curr Diabetes Rev 2006; 2: 3-9
    CrossrefPubMedGoogle Scholar
  • 12 Brennand K, Melton D. Slow and steady is the key to beta-cell replication. J Cell Mol Med 2009; 13: 472-487
    CrossrefPubMedGoogle Scholar
  • 13 Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D’Amour KA, Carpenter MK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26: 443-452
    CrossrefPubMedGoogle Scholar
  • 14 Ludwig B, Ludwig S, Steffen A, Saeger HD, Bornstein SR. Islet versus pancreas transplantation in type 1 diabetes: competitive or complementary?. Curr Diab Rep 2010; 10: 506-511
    CrossrefPubMedGoogle Scholar
  • 15 McCall MD, Toso C, Baetge EE, Shapiro AM. Are stem cells a cure for diabetes?. Clin Sci (Lond) 2010; 118: 87-97
    PubMedGoogle Scholar
  • 16 Schulz TC, Young HY, Agulnick AD, Babin MJ, Baetge EE, Bang AG, Bhoumik A, Cepa I, Cesario RM, Haakmeester C, Kadoya K, Kelly JR, Kerr J, Martinson LA, McLean AB, Moorman MA, Payne JK, Richardson M, Ross KG, Sherrer ES, Song X, Wilson AZ, Brandon EP, Green CE, Kroon EJ, Kelly OG, D’Amour KA, Robins AJ. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS One 2012; 7: e37004
    CrossrefPubMedGoogle Scholar
  • 17 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676
    CrossrefPubMedGoogle Scholar
  • 18 Weir GC, Cavelti-Weder C, Bonner-Weir S. Stem cell approaches for diabetes: towards beta cell replacement. Genome Med 2011; 3: 61
    CrossrefPubMedGoogle Scholar
  • 19 Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, Shi Y, Deng H. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 2009; 19: 429-438
    CrossrefPubMedGoogle Scholar
  • 20 Sollinger HW, Odorico JS, Becker YT, D’Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg 2009; 250: 618-630
    PubMedGoogle Scholar
  • 21 Bromberg JS, Kaplan B, Halloran PF, Robertson RP. The islet transplant experiment: time for a reassessment. Am J Transplant 2007; 7: 2217-2218
    CrossrefPubMedGoogle Scholar
  • 22 Cravedi P, Mannon RB, Ruggenenti P, Remuzzi A, Remuzzi G. Islet transplantation: need for a time-out?. Nat Clin Pract Nephrol 2008; 4: 660-661
    CrossrefPubMedGoogle Scholar
  • 23 Lehmann R, Spinas GA, Moritz W, Weber M. Has time come for new goals in human islet transplantation?. Am J Transplant 2008; 8: 1096-1100
    CrossrefPubMedGoogle Scholar
  • 24 Thompson DM, Meloche M, Ao Z, Paty B, Keown P, Shapiro RJ, Ho S, Worsley D, Fung M, Meneilly G, Begg I, Al Mehthel M, Kondi J, Harris C, Fensom B, Kozak SE, Tong SO, Trinh M, Warnock GL. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 2011; 91: 373-378
    CrossrefPubMedGoogle Scholar
  • 25 Takita M, Matsumoto S, Shimoda M, Chujo D, Itoh T, Sorelle JA, Purcell K, Onaca N, Naziruddin B, Levy MF. Safety and tolerability of the T-cell depletion protocol coupled with anakinra and etanercept for clinical islet cell transplantation. Clin Transplant 2012; 26: E471-E484
    CrossrefPubMedGoogle Scholar
  • 26 Alejandro R, Barton FB, Hering BJ, Wease S. Update from the Collaborative Islet Transplant Registry. Transplantation 2008; 86: 1783-1788
    CrossrefPubMedGoogle Scholar
  • 27 Berney T, Johnson PR. Donor pancreata: evolving approaches to organ allocation for whole pancreas versus islet transplantation. Transplantation 2010; 90: 238-243
    PubMedGoogle Scholar
  • 28 Collett D, Johnson R, Hudson A, Neuberger J. Organ allocation in the United Kingdom. Clin Transpl 2010; 24: 53-60
    PubMedGoogle Scholar
  • 29 Ridgway DM, White SA, Kimber RM, Nicholson ML. Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation. Transpl Int 2005; 18: 828-834
    CrossrefPubMedGoogle Scholar