Transplantations in patients with diabetes mellitus

Epidemiological studies clearly demonstrate that every other patient suffering from diabetes mellitus will develop diabetic secondary complications affecting the eyes, kidneys, the cardiovascular system or the peripheral or autonomic nerve system. These chronic organ lesions may end up in organ failure, i.e. end-stage renal failure, myocardial infarction, and congestive heart failure. In Germany, about 13,000 diabetic patients are currently included in chronic dialysis programs and the incidence is calculated to 4,000 new cases per year [1, 2]. Approximately 35,000 diabetic subjects per year die from myocardial infarction [3]. This is not surprising in the light of present findings, that the 7 years-risk for myocardial infarction, stroke, and death of a type-2 diabetic subject without prior myocardial infarction compares to that of a non-diabetic subject who had already a myocardial infarction [4]. Furthermore, mortality of diabetic patients who develop acute myocardial infarction is high and exceeds that of non-diabetic patients despite invasive therapy [5].

Since the invention of sucessful immunosuppressive substances, organ transplantation has become a powerful measure for organ replacement therapy in case of organ failure. The world experience tells us that by the end of 1998 a total of 447,182 patients were kidney transplanted, 72,311 patients received a liver graft, 49,829 patients had a heart transplantation and 8,842 patients were lung transplanted [6]. The longest surviving is reported as 35 years for a kidney graft, 28 year for a liver graft, 23 years for a heart transplant, and 11 years for a lung graft [6].

In contrast, patients with diabetes mellitus were for a long time almost totally excluded from organ transplant programs and they are still underrepresented on the waiting lists. Reasons might be the very often poor general condition of these patients, their high risk for infections and their concomitant increased cardiovascular risk. However, the more aggressive testing for cardiovascular risk factors before including a patient in the waiting list for organ transplantation should equalize the differences between diabetic and non-diabetic candidates for organ grafts. Furthermore, powerful tools to treat eventually occurring infections in immunosuppressed patients and the use of less diabetogenic immunosuppressants may improve the organ transplantation outcomes in diabetic patients to a level seen in non-diabetic recipients.

During the Annual Meeting of the German Diabetes Association 1999, a main session was devoted to the topic “Transplantations in Diabetic Patients”. It covered dialysis treatment as a prerequisite to bridge for kidney grafting, kidney transplantations, heart transplantations, and liver transplantations in patients with diabetes mellitus. Several presentations were given to the state-of-the-art of pancreatic and pancreatic islet cell transplantation. These transplantations are performed in order to re-establish blood glucose homeostasis avoiding insulin injections, to arrest the progress of ongoing secondary complications, and to improve quality of life. By the end of 1998, more than 11,000 pancreatic organ transplantations had been recorded in the International Pancreas Transplant Registry [7]. Pancreas transplantation should be considered an acceptable therapeutic alternative to continued insulin therapy at least in diabetic patients with imminent or established end-stage renal disease who have had or plan to have a kidney transplant [8]. In the simultaneous pancreas-kidney recipient category, the one-year survival rate was found ≥90% both for patients and kidney and > 80% for the pancreas graft [7]. Furthermore, long-term studies described a substantial reduction in mortality in type-1 diabetic patients 10 years after successful pancreas-kidney transplantation and therefore suggest that combined pancreas and kidney transplantation, rather than kidney transplantation alone, should be offered to type-1 diabetic patients with end-stage renal failure [9]. Albeit clinical pancreatic islet cell transplantations hold potential advantages and have made significant progress in recent years, this method is to some extent still an investigational procedure [10, 11].

In this issue of Experimental and Clinical Endocrinology & Diabetes, the first of a comprehensive series of reports given at the 1999 Annual Meeting of the German Diabetes Association will be published. Its topic is cardiac transplantation in patients with diabetes mellitus and it presents original work of the Herz- und Diabeteszentrum Bad Oeynhausen [12]. Original articles and overviews dealing with other types of organ and cell transplantations in patients with diabetes mellitus will follow.

We do hope, that these series of articles will find the interest of the readers of this journal. The main message from these reports might be that it is no longer justified to exclude diabetic patients from the benefits of organ transplantations.

References

• 1 Koch M, Thomas B, Tschöpe W, Ritz E. Diabetes mellitus accounts for an ever-increasing proportion of the patients admitted for renal replacement therapy.  Nephrol Dial Transplant. 4 399 1989 [Letter]; 
• 2 Lippert J, Ritz E, Schwarzbeck A, Schneider P. The rising tide of endstage renal failure from diabetic nephropathy type II - and epidemiologic analysis.  Nephrol Dial Transplant. 10 462-467 1995; 
• 3 Löwel H, Stieber J, König W, Thorand B, Hörmann A, Gostomzyk J, Keil U. Das Diabetes-bedingte Herzinfarktrisiko in einer süddeutschen Bevölkerung: Ergebnisse der MONICA-Augsburg-Studie 1985-1994.  Diabetes Stoffw. 8 11-21 1999; 
• 4 Haffner S M, Lehto S, Rönnema T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.  N Engl J Med. 339 229-234 1998; 
• 5 Waldecker B, Waas W, Haberbosch W, Voss R, Steen-Müller M K, Hiddessen A, Bretzel R, Tillmanns H. Type 2 diabetes and acute myocardial infarction. Angiographic findings of an invasive therapeutic approach in type 2 diabetic versus nondiabetic patients.  Diabetes Care. 22 1832-1838 1999; 
• 6 Cecka J M, Terasaki P I. Clinical Transplants 1998. UCLA Tissue Typing Laboratory, Los Angeles, USA 1999
• 7 Bland B J. International Pancreas Transplant Registry.  Newsletter. 11 1-19 1999; 
• 8 American Diabetes Association . Pancreas Transplantation for patients with type 1 diabetes.  Diabetes Care. 23 117 2000; 
• 9 Tyden G, Bolinder J, Solders G, Brattström C, Tibell A, Groth C-G. Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation.  Transplantation. 67 645-648 1999; 
• 10 Brendel M D, Hering B J, Schultz A O, Bretzel R G. International Islet Transplant.  Registry. Newsletter. 8 1-20 1999; 
• 11 Bretzel R G, Brandhorst D, Brandhorst H, Eckhard M, Ernst W, Friemann S, Rau W, Weimar B, Rauber K, Hering B J, Brendel M D. Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management.  J Mol Med. 77 140-143 1999; 
• 12 Tenderich G, Schulte-Eistrup S, Petzoldt R, Koerfer R. Cardiac transplantation in patients with type-1/2 insulin treated diabetes mellitus.  Exp Clin Endocrinol Diabetes. 108 249-252 2000 (this issue);