Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Diabetes ; 64(5): 1713-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25524910

ABSTRACT

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.


Subject(s)
Blood Glucose/physiology , Diabetes Mellitus, Type 1/therapy , Glucose/metabolism , Islets of Langerhans Transplantation/physiology , Adult , Female , Glucose Clamp Technique , Humans , Male , Middle Aged
2.
Transplantation ; 88(6): 820-5, 2009 Sep 27.
Article in English | MEDLINE | ID: mdl-19920782

ABSTRACT

BACKGROUND: Isolated islet transplantation with infusions from two to three donor pancreata and Edmonton immunosuppression consistently achieves insulin independence in patients with type 1 diabetes. The success of this protocol has been attributed to a novel combination of immunosuppressive agents and avoidance of steroids; however, the outcome of islet transplantation may differ in kidney transplant recipients who are already immunosuppressed. METHODS: We compared the metabolic outcomes and graft survival of islet transplantation in our program where nine patients underwent islet transplantation alone treated with Edmonton immunosuppression and eight patients received islet after kidney (IAK) transplants under standard kidney transplant immunosuppression often including steroids. RESULTS: Transplants in the IAK and islet transplantation alone setting demonstrated similar islet potency (islet equivalents/unit insulin reduction) and recipients from both groups routinely gained insulin independence, functional islet mass, and duration of graft survival, however, seemed superior in the IAK group. CONCLUSIONS: These results suggest that better islet graft function and survival may be attained using non-Edmonton rather than Edmonton immunosuppression and can include maintenance steroid therapy.


Subject(s)
Islets of Langerhans Transplantation/methods , Islets of Langerhans Transplantation/physiology , Kidney Transplantation/methods , Adult , Blood Glucose/metabolism , C-Peptide/blood , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/surgery , Female , Glycated Hemoglobin/metabolism , Graft Survival/physiology , Humans , Immunosuppression Therapy/methods , Insulin/administration & dosage , Male , Middle Aged , Time Factors
3.
Clin Transpl ; : 413-20, 2006.
Article in English | MEDLINE | ID: mdl-18365398

ABSTRACT

Islet transplantation is an emerging therapy for poorly controlled type 1 diabetes. Currently, islets isolated from multiple donors not HLA-matched to recipients are usually required to achieve insulin-independence. Subsequent HLA sensitization is common following a reduction or discontinuation of immunosuppressive drugs and may be responsible for deterioration in islet graft function. Based on the evidence available to date concerning HLA sensitization in islet transplant recipients, we recommend that future islet transplantation protocols consider the following: (1) minimizing the number of islet donors by, for example, infusing high quality islet preparations of sufficient yield from a single donor rather than pooling islet preparations from multiple donors since a greater number of HLA class I mismatches appears to be associated with increased risk for sensitization; (2) ensuring negative cross-matching of donor lymphocytes and recipient sera by testing prior to islet infusions; (3) avoiding donor-recipient antigen mismatches when an identifiable alloantibody is present pre-transplant (i.e., in the case of a positive PRA pretransplant) but excluding potential recipients who are highly sensitized (e.g., have a PRA > or = 20%); and (4) performing an assessment for HLA sensitization using a sensitive flow cytometric method for alloantibody detection any time there is a reduction in immunosuppressant drug levels or worsening of metabolic control.


Subject(s)
HLA Antigens/immunology , Immunization , Islets of Langerhans Transplantation/immunology , Adult , Diabetes Mellitus, Type 1/surgery , Female , Histocompatibility Testing , Humans , Male , Middle Aged
4.
Ann Surg ; 240(4): 631-40; discussion 640-3, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15383791

ABSTRACT

OBJECTIVE: We sought to compare the efficacy, risks, and costs of whole-organ pancreas transplantation (WOP) with the costs of isolated islet transplantation (IIT) in the treatment of patients with type I diabetes mellitus. SUMMARY BACKGROUND DATA: A striking improvement has taken place in the results of IIT with regard to attaining normoglycemia and insulin independence of type I diabetic recipients. Theoretically, this minimally invasive therapy should replace WOP because its risks and expense should be less. To date, however, no systematic comparisons of these 2 options have been reported. METHODS: We conducted a retrospective analysis of a consecutive series of WOP and IIT performed at the University of Pennsylvania between September 2001 and February 2004. We compared a variety of parameters, including patient and graft survival, degree and duration of glucose homeostasis, procedural and immunosuppressive complications, and resources utilization. RESULTS: Both WOP and IIT proved highly successful at establishing insulin independence in type I diabetic patients. Whole-organ pancreas recipients experienced longer lengths of stay, more readmissions, and more complications, but they exhibited a more durable state of normoglycemia with greater insulin reserves. Achieving insulin independence by IIT proved surprisingly more expensive, despite shorter initial hospital and readmission stays. CONCLUSION: Despite recent improvement in the success of IIT, WOP provides a more reliable and durable restoration of normoglycemia. Although IIT was associated with less procedure-related morbidity and shorter hospital stays, we unexpectedly found IIT to be more costly than WOP. This was largely due to IIT requiring islets from multiple donors to gain insulin independence. Because donor pancreata that are unsuitable for WOP can often be used successfully for IIT, we suggest that as IIT evolves, it should continue to be evaluated as a complementary alternative to rather than as a replacement for the better-established method of WOP.


Subject(s)
Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation , Pancreas Transplantation , Adult , Blood Glucose/analysis , Female , Graft Survival , Health Care Costs , Health Resources/statistics & numerical data , Homeostasis , Humans , Immunosuppression Therapy/adverse effects , Insulin/blood , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/economics , Length of Stay , Male , Middle Aged , Minimally Invasive Surgical Procedures , Pancreas Transplantation/adverse effects , Pancreas Transplantation/economics , Patient Readmission , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome
5.
Ann Surg ; 237(6): 741-9; discussion 749-50, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12796569

ABSTRACT

OBJECTIVE: To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. SUMMARY BACKGROUND DATA: The recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. METHODS: The authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. RESULTS: In each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. CONCLUSIONS: This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.


Subject(s)
Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation , Recovery of Function , Adult , Blood Glucose/analysis , C-Peptide/blood , Diabetes Mellitus, Type 1/blood , Humans , Immunosuppressive Agents/therapeutic use , Islets of Langerhans Transplantation/immunology , Islets of Langerhans Transplantation/methods
6.
Transplantation ; 76(11): 1623-5, 2003 Dec 15.
Article in English | MEDLINE | ID: mdl-14702535

ABSTRACT

The recent success of islet transplantation using the Edmonton protocol involved the use of sirolimus, tacrolimus, and daclizumab for immunosuppression. Islets were infused into the portal circulation after transhepatic access. This protocol provided a unique opportunity to measure sirolimus and tacrolimus levels from the portal vein and compare them to systemic venous levels. A total of 11 portal venous samples with a corresponding peripheral venous sample were obtained from patients undergoing a first or second islet infusion and medication levels were obtained on both types of specimens. The portal-to-systemic drug level ratio ranged from 0.95 to 2.71 for sirolimus and 1.0 to 3.12 for tacrolimus. Given the potential toxicity of these agents to islets, the findings in this study may have implications for designing the next generation of immunosuppressive protocols for islet transplantation.


Subject(s)
Islets of Langerhans Transplantation/immunology , Islets of Langerhans/pathology , Portal Vein/physiology , Sirolimus/blood , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Portal System , Regression Analysis , Sirolimus/pharmacokinetics , Sirolimus/therapeutic use
7.
Transplantation ; 74(2): 169-72, 2002 Jul 27.
Article in English | MEDLINE | ID: mdl-12151727

ABSTRACT

BACKGROUND: Minimally invasive donor nephrectomy has become a favored procedure for the procurement of kidneys from live donors. The optimal minimally invasive surgical approach has not been determined. In the current work, we compared the outcome of kidneys procured using the traditional open approach with two minimally invasive techniques: the standard laparoscopic procedure and a hand-assist procedure. METHODS: The function of live-donor kidneys procured by open versus minimally invasive procedures was compared (procedures compared were the traditional open donor nephrectomy [ODN], the standard laparoscopic [LAP] approach, and the hand-assisted [HA] laparoscopic technique). The length of donor operation, donor length of stay in the hospital, surgical complications, and cost of hospitalization for three groups of patients were assessed in a series of 150 live-donor nephrectomies. RESULTS: We found that both minimally invasive procedures yielded kidney allografts with excellent early function and a minimum of complications in the donor. The open procedure was associated with a reduced operative time but increased donor length of stay in the hospital. Resource utilization analysis revealed that both minimally invasive techniques were associated with a slight increase in costs compared with the open procedure, despite a shorter hospital stay. CONCLUSIONS: Minimally invasive donor nephrectomy is safe and effective for procuring normally functioning organs for live-donor transplantation. Of the two minimally invasive approaches examined, the hand-assisted technique was found to afford a number of important advantages, including facilitating teaching of residents and students, that it is more readily mastered by transplant surgeons, and that it may provide an additional margin of safety for the donor.


Subject(s)
Kidney Transplantation , Laparoscopy/methods , Nephrectomy/methods , Tissue Donors , Adult , Humans , Male , Middle Aged , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...