- Email: [email protected]
Eligibility of diabetic patients for islet transplantation alone
Eligibility of Diabetic Patients for Islet Transplantation Alone M.C. Vantyghem, P. Perimenis, S. Tourvieille, L. Touzet, and F. Pattou ABSTRACT Since the Edmonton protocol, islet transplantation alone (ITA) offers the prospect of adequate glycemic control in type 1 diabetes without kidney failure. Patient motivation, evolution of diabetic complications, and hypoglycemia unawareness have to be balanced against the risks of portal puncture and long-term immunosuppressive therapy. The aim of this work was to assess the profile of 41 type 1 diabetic patients (21 men and 20 women of age 18 to 63 years) for whom islet transplantation was considered, between January 2000 and December 2002. Thirty-one of these patients lived in the area. The patients were divided into 3 groups according to their recruitment: 20, personal initiative (G1); 8, recruited from hospitalization (G2) for marked glycemic imbalance; and 13, (G3) referred by their diabetologist. Among this series of 41 patients, 14 (8 in G1, 4 in G2, and 2 in G3) did not fit the eligibility criteria, mainly because of a positive C-peptide, kidney failure, desire for pregnancy (G1, G3), liver disorders related to alcohol or iron overload related to HFE heterozygosity (G2), or good glycemic balance (G3). Sixteen did not wish to proceed after the first information step, 6 of these being more interested in a pump. Eleven, mainly recruited in G1 or G3, went through the clinical pretransplantation assessment. Among these, 2 have undergone transplantation, another 1 is enlisted. Therefore, it appears that patient motivation and information to the diabetologists are two important issues in the recruitment of patients eligible for islet transplantation. Equally important is the measurement of C-peptide, plasma creatinine, and microalbuminuria.
S
INCE the Edmonton protocol, isolated islet transplantation offers the prospect of good glycemic control with no major surgical risk in patients with type 1 diabetes without kidney failure.1–3 Moreover, recent studies have shown that islet transplantation can compare with pancreas transplantation in terms of improvement of diabetic complications.4 Nevertheless, eligibility criteria for this strategy have yet to be perfectly defined. Patient motivation, evolution of diabetic complications, and hypoglycemia unawareness have to be balanced against the risks of portal puncture and long-term immunosuppressive therapy. An attempt at quantified standardization of hypoglycemia unawareness and glycemic lability is currently being evaluated.5 The aim of our work was to assess the profile of type 1 diabetic patients for islet transplantation. PATIENTS Between January 2000 and December 2002, 41 diabetic patients including 21 men and 20 women from 18 to 63 years of age included 31 from the area and 10 from other areas. The patients were divided into 3 groups according to their mode of recruitment. For 20 it was a personal initiative (G1), all of whom received informa-
tion either by letter or via an information booklet; their family doctors also were informed. Eight were recruited from hospitalization (G2) for marked glycemic imbalance with either severe ketoacidosis or hypoglycemia. The remaining 13 (G3) were referred by their diabetologist.
RESULTS
Among the patients for who it was a personal initiative, 6 of 20 did not meet the transplantation criteria: 2 had Cpeptide positive diabetes, another 2 had increased creatinine levels, and the last 2 (females) were considering From the Endocrinology and Metabolism Department (M.C.V., P.P., S.T.), Department of Endocrine Surgery (F.P.), INSERM ERIT 0106 (M.C.V., L.T., F.P.), Lille University Hospital, Lille, France. This article was supported by a grant from the Hospital Project for Clinical Research (PHRC). Address reprint requests to M.C. Vantyghem, Endocrinology and Metabolism Department, 6, rue du Professeur Laguesse, Centre Hospitalo-Universitaire, 59037 Lille Cedex, France. Email: [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.04.031
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1106
Transplantation Proceedings, 36, 1106 –1107 (2004)
DIABETIC PATIENTS AND ITA
Fig 1.
1107
Flowchart of diabetic patients for whom islet transplantation has been considered.
pregnancy. Seven of 20 did not return after having received information. The last 7 of 20 were seen at the clinic; another 2 women were considering pregnancy. Five men agreed to undergo further investigation, among whom 2 have received transplants, 1 in Lille, the other 1 in Islet Transplantation Network. The other 3 patients who have undergone pretransplantation clinical evaluation are currently treated with a pump, but all 3 have hypoglycemia unawareness. Among the 8 who were recruited from hospitalization for marked glycemic imbalance, 4 of 8 had problems with alcohol, 2 of whom had hepatopathy related to iron overload related to HFE heterozygoty; the other 2 were not interested. Among the last 2, 1 chose an insulin pump and the last 1 is undergoing further evaluation. Among the 13 patients referred by a diabetologist, 1 is currently on the waiting list, another 4 are undergoing evaluation, 6 are considering a pump or have been implanted, and 2 did not fit the inclusion criteria either for kidney failure or, on the contrary, for very good glycemic balance. DISCUSSION
Our aim was to assess the profile of type 1 diabetic patients for islet transplantation. The patients were divided into 3 groups according to their mode of recruitment: personal initiative (G1; n ⫽ 21), hospitalization for marked glycemic imbalance (G2; n ⫽ 8), or referral by the diabetologist (G3; n ⫽ 13). Among this series of 41 diabetic patients, 14 did not fit the eligibility criteria, mainly for satisfactory glycemic balance (n ⫽ 1), positive C-peptide (n ⫽ 2), kidney failure (n ⫽ 3), desire for pregnancy (n ⫽ 4), or liver problems (n ⫽ 4). Sixteen did not go further after the first information step, 7 of these being more interested in a pump. Eleven undertook pretransplantation assessment, mainly recruited in groups G1 and G3. Two of 11 have received transplants. One of 11 is enlisted. Eight of 11 are currently undergoing pretransplantation clinical investigation (Fig 1). This study suggests that patients seen in the emergency room for serious diabetic imbalance are not good candidates for islet transplantation (1 of 8 patients in G2 recruited for further evaluation, whereas 5 of 20 were recruited in group G1 and another 5 of 13 in group G3). Moreover, in France, islet transplantation may be in competition with external pumps of insulin, which are covered by health insurance, especially
for patients aware of their hypoglycemias. However, a recent communication comparing the results of islet or pancreas transplantation versus subcutaneous or intraperitoneal delivery of insulin with a pump demonstrated the superiority of glycemic balance obtained after transplantation.6 All in all, about 25% of the patients for whom islet transplantation has been considered underwent pretransplantation assessment. The main reasons for excluding patients from the islet transplant protocol (which is still a part of clinical research in France) were a desire for pregnancy in young women, as the risk of immunosuppressive therapy for the infant is not documented, beginning kidney failure, difficult situation in which no standard therapy is proposed, and liver problems related to alcohol or iron overload (linked to HFE heterozygosity) because this may increase the risk of hepatocarcinoma, especially under immunosuppressive therapy. In conclusion, according to the analysis of our series, the constitution of active files of patients eligible for islet transplantation requires that both patients and diabetologists be informed. Patients seen in the emergency room with poor glycemic balance are rarely good candidates for islet transplantation. REFERENCES 1. Shapiro AM, Lakey JRT, Ryan EA, et al: Islet transplantation in seven patients with type 1 diabetes. N Engl J Med 34:230, 2000 2. Ryan EA, Lakey JR, Paty BW, et al: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51:2148, 2002 3. Pattou F, Vantyghem MC, Noel C, et al: Sequential intraportal islet allografts in immunosuppressed type I diabetic patients: preliminary results. Transplant Proc 32:391, 2000 4. Fioretto P, Folli F, Maffi P, et al: Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation. Transplantation 75:1296, 2003 5. Ryan E, Shandro T, Vantyghem MC, et al: Assessing severity of hypoglycemia and glycemic lability pre and post islet transplant. Diabetes 52(suppl 1):A67, 2003 6. Kessler L, Passemard R, Oberholzer J, et al: Reduction of blood glucose variability in type 1 diabetic patients treated by pancreatic islet transplantation: interest of continuous glucose monitoring. Diabetes Care 25:2256, 2002
S
INCE the Edmonton protocol, isolated islet transplantation offers the prospect of good glycemic control with no major surgical risk in patients with type 1 diabetes without kidney failure.1–3 Moreover, recent studies have shown that islet transplantation can compare with pancreas transplantation in terms of improvement of diabetic complications.4 Nevertheless, eligibility criteria for this strategy have yet to be perfectly defined. Patient motivation, evolution of diabetic complications, and hypoglycemia unawareness have to be balanced against the risks of portal puncture and long-term immunosuppressive therapy. An attempt at quantified standardization of hypoglycemia unawareness and glycemic lability is currently being evaluated.5 The aim of our work was to assess the profile of type 1 diabetic patients for islet transplantation. PATIENTS Between January 2000 and December 2002, 41 diabetic patients including 21 men and 20 women from 18 to 63 years of age included 31 from the area and 10 from other areas. The patients were divided into 3 groups according to their mode of recruitment. For 20 it was a personal initiative (G1), all of whom received informa-
tion either by letter or via an information booklet; their family doctors also were informed. Eight were recruited from hospitalization (G2) for marked glycemic imbalance with either severe ketoacidosis or hypoglycemia. The remaining 13 (G3) were referred by their diabetologist.
RESULTS
Among the patients for who it was a personal initiative, 6 of 20 did not meet the transplantation criteria: 2 had Cpeptide positive diabetes, another 2 had increased creatinine levels, and the last 2 (females) were considering From the Endocrinology and Metabolism Department (M.C.V., P.P., S.T.), Department of Endocrine Surgery (F.P.), INSERM ERIT 0106 (M.C.V., L.T., F.P.), Lille University Hospital, Lille, France. This article was supported by a grant from the Hospital Project for Clinical Research (PHRC). Address reprint requests to M.C. Vantyghem, Endocrinology and Metabolism Department, 6, rue du Professeur Laguesse, Centre Hospitalo-Universitaire, 59037 Lille Cedex, France. Email: [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.04.031
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1106
Transplantation Proceedings, 36, 1106 –1107 (2004)
DIABETIC PATIENTS AND ITA
Fig 1.
1107
Flowchart of diabetic patients for whom islet transplantation has been considered.
pregnancy. Seven of 20 did not return after having received information. The last 7 of 20 were seen at the clinic; another 2 women were considering pregnancy. Five men agreed to undergo further investigation, among whom 2 have received transplants, 1 in Lille, the other 1 in Islet Transplantation Network. The other 3 patients who have undergone pretransplantation clinical evaluation are currently treated with a pump, but all 3 have hypoglycemia unawareness. Among the 8 who were recruited from hospitalization for marked glycemic imbalance, 4 of 8 had problems with alcohol, 2 of whom had hepatopathy related to iron overload related to HFE heterozygoty; the other 2 were not interested. Among the last 2, 1 chose an insulin pump and the last 1 is undergoing further evaluation. Among the 13 patients referred by a diabetologist, 1 is currently on the waiting list, another 4 are undergoing evaluation, 6 are considering a pump or have been implanted, and 2 did not fit the inclusion criteria either for kidney failure or, on the contrary, for very good glycemic balance. DISCUSSION
Our aim was to assess the profile of type 1 diabetic patients for islet transplantation. The patients were divided into 3 groups according to their mode of recruitment: personal initiative (G1; n ⫽ 21), hospitalization for marked glycemic imbalance (G2; n ⫽ 8), or referral by the diabetologist (G3; n ⫽ 13). Among this series of 41 diabetic patients, 14 did not fit the eligibility criteria, mainly for satisfactory glycemic balance (n ⫽ 1), positive C-peptide (n ⫽ 2), kidney failure (n ⫽ 3), desire for pregnancy (n ⫽ 4), or liver problems (n ⫽ 4). Sixteen did not go further after the first information step, 7 of these being more interested in a pump. Eleven undertook pretransplantation assessment, mainly recruited in groups G1 and G3. Two of 11 have received transplants. One of 11 is enlisted. Eight of 11 are currently undergoing pretransplantation clinical investigation (Fig 1). This study suggests that patients seen in the emergency room for serious diabetic imbalance are not good candidates for islet transplantation (1 of 8 patients in G2 recruited for further evaluation, whereas 5 of 20 were recruited in group G1 and another 5 of 13 in group G3). Moreover, in France, islet transplantation may be in competition with external pumps of insulin, which are covered by health insurance, especially
for patients aware of their hypoglycemias. However, a recent communication comparing the results of islet or pancreas transplantation versus subcutaneous or intraperitoneal delivery of insulin with a pump demonstrated the superiority of glycemic balance obtained after transplantation.6 All in all, about 25% of the patients for whom islet transplantation has been considered underwent pretransplantation assessment. The main reasons for excluding patients from the islet transplant protocol (which is still a part of clinical research in France) were a desire for pregnancy in young women, as the risk of immunosuppressive therapy for the infant is not documented, beginning kidney failure, difficult situation in which no standard therapy is proposed, and liver problems related to alcohol or iron overload (linked to HFE heterozygosity) because this may increase the risk of hepatocarcinoma, especially under immunosuppressive therapy. In conclusion, according to the analysis of our series, the constitution of active files of patients eligible for islet transplantation requires that both patients and diabetologists be informed. Patients seen in the emergency room with poor glycemic balance are rarely good candidates for islet transplantation. REFERENCES 1. Shapiro AM, Lakey JRT, Ryan EA, et al: Islet transplantation in seven patients with type 1 diabetes. N Engl J Med 34:230, 2000 2. Ryan EA, Lakey JR, Paty BW, et al: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51:2148, 2002 3. Pattou F, Vantyghem MC, Noel C, et al: Sequential intraportal islet allografts in immunosuppressed type I diabetic patients: preliminary results. Transplant Proc 32:391, 2000 4. Fioretto P, Folli F, Maffi P, et al: Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation. Transplantation 75:1296, 2003 5. Ryan E, Shandro T, Vantyghem MC, et al: Assessing severity of hypoglycemia and glycemic lability pre and post islet transplant. Diabetes 52(suppl 1):A67, 2003 6. Kessler L, Passemard R, Oberholzer J, et al: Reduction of blood glucose variability in type 1 diabetic patients treated by pancreatic islet transplantation: interest of continuous glucose monitoring. Diabetes Care 25:2256, 2002