ABSTRACT
DESIGN: Successful pancreas transplantation results in insulin independence and normoglycemia. This prospective study was performed to investigate long-term metabolic changes after pancreas transplantation. METHODS: Thirty-eight type 1 diabetic patients after simultaneous pancreas/kidney transplantation (SPK) with a pancreas graft survival for at least 10 years were studied in a prospective manner. HbA(1c) and glucose levels before and during an oral glucose tolerance test (OGTT) were analyzed from 3 months to 10 years after SPK. In addition, insulin secretion and glucagon response were measured. RESULTS: Fasting glucose increased slightly and continuously from 3 months to 10 years (from 78 +/- 3 to 91 +/- 2 mg/dl). Even HbA(1c) levels showed a mild but significant increase from 3 months to 10 years after SPK. Glucose tolerance deteriorated markedly 10 years after SPK. Insulin secretion during OGTT remained stable for 10 years. Parameters of insulin resistance and sensitivity did not change significantly but glucagon secretion increased significantly during the course after SPK. Late after SPK, glucagon levels were higher in patients with an impaired or diabetic glucose tolerance. CONCLUSIONS: Pancreas transplantation is able to restore endogenous insulin secretion for 10 years or more. Especially, late after SPK, a deterioration of glycemic control was detected, even if glucose values were within the normal range. During prospective long-term follow-up, an increase of glucagon secretion but no decrease of insulin secretion was detected.
Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Pancreas Transplantation/methods , Adult , Area Under Curve , Blood Glucose/metabolism , Female , Follow-Up Studies , Glucagon/blood , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Graft Survival , Humans , Insulin/blood , Male , Prospective Studies , Statistics, NonparametricABSTRACT
INTRODUCTION: Pulmonary function is impaired in type 1 diabetes mellitus and is associated with the quality of metabolic control. Correction of chronic hyperglycemia by pancreas transplantation may ameliorate pulmonary function. METHODS: Lung volume and diffusing capacity were measured in 75 uremic patients with type 1 diabetes and a long diabetes duration waiting for a simultaneous kidney and pancreas transplantation (SPK). In addition 85 patients after SPK and 20 patients after kidney transplantation alone (KA) were investigated. In a subgroup of 30 patients, data before and after SPK were available for prospective analysis. RESULTS: Reduced lung volume and diffusing capacity were found in type 1 diabetic patients before transplantation. Nearly all parameters of pulmonary function improved after SPK and KA. A significant change was found for forced expiratory volume at 1 sec (FEV1) and FEV1/forced vital capacity (FVC) (Tiffenau index). A significant amelioration of diffusing capacity was only found in the SPK group but not in the KA group. The prospective investigation revealed significant improvements of pulmonary function after SPK: FEV1 (P=0.001), FVC, (P=0,006), Tiffenau index (P=0.03), and Hb-corrected diffusing capacity (carbon monoxide transfer factor, TCO), P=0.03; transfer coefficient (KCO=TCO corrected for alveolar volume), P=0.01. CONCLUSION: Simultaneous pancreas and kidney transplantation is able to attain long-term normoglycemia and to improve pulmonary function in uremic type 1 diabetic patients.
Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Kidney Failure, Chronic/surgery , Kidney Transplantation/physiology , Pancreas Transplantation/physiology , Respiratory Function Tests , Adult , Diabetic Nephropathies/physiopathology , Female , Forced Expiratory Volume , Glycated Hemoglobin/analysis , Humans , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Postoperative Period , Preoperative Care , Reference Values , Vital Capacity , Waiting ListsABSTRACT
Autoimmune recurrence and subsequent diabetes after pancreas transplantation has been described. In this cross-sectional study 91 type 1 diabetic patients were examined after successful pancreas/kidney transplantation (SPK). We studied the prevalence of autoantibodies to insulin (IAA), glutamate decarboxylase (GAD) and tyrosine phosphatase (IA-2) as well as parameters of pancreas graft function. Graft recipients were grouped according to immunoreactivity: group 1: no immunoreactivity; group 2: immunoreactivity to one antigen; group 3: immunoreactivity to two or three antigens. Twenty-five percent of graft recipients displayed no immunoreactivity, 39% displayed positivity for one antigen and 36% were positive for two or three antigens. There were no significant differences concerning fasting glucose, HbA1(c), glucose tolerance and renal function between the groups. Patients with cyclosporine (n = 42) as first-line immunosuppression displayed more often immunoreactivity to IA-2 and IAA than patients treated with tacrolimus (n = 49) (31% vs. 14%, P = 0.04; 67% vs. 47%, P = 0.04). In addition methylprednisolone therapy was related to less immunoreactivity to IA-2. Immunological markers for type 1 diabetes can be determined in the majority of pancreas graft recipients despite adequate immunosuppression. However, immunoreactivity was not associated with impaired graft function. Patients with cyclosporine for immunosuppression and withdrawal of glucocorticoids therapy were more often immunoreactive to IAA and IA-2.
Subject(s)
Autoantibodies/chemistry , Islets of Langerhans/immunology , Pancreas Transplantation/methods , Adult , Autoimmune Diseases/diagnosis , Blood Glucose/metabolism , Female , Glucocorticoids/metabolism , Glucose/metabolism , Glucose Tolerance Test , Glutamate Decarboxylase/immunology , Graft Rejection , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Insulin/metabolism , Male , Methylprednisolone/therapeutic use , Middle Aged , Models, Statistical , Pancreas/immunology , Pancreas Transplantation/adverse effects , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases/chemistry , Protein Tyrosine Phosphatases/immunology , Recurrence , Tacrolimus/pharmacology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The results of the new immunosuppressants in simultaneous pancreas-kidney transplantation (SPK) concerning organ survival and rejection rates are excellent. Tacrolimus as well as cyclosporine are assumed to be diabetogenic; however, there are no comparative studies investigating their effects on glucose metabolism. METHODS: One hundred thirty-six type 1 diabetic patients who had undergone successful SPK were investigated. Glucose and insulin levels during an oral glucose tolerance test as well as hemoglobin (Hb) A1c were analyzed. Investigations were performed early (3 months, n = 136) and late (3 years, n = 83) after transplantation. Graft recipients were grouped according to the first-line immunosuppression: group 1, cyclosporine; group 2, tacrolimus. There were no differences concerning age, gender, body mass index, and renal function between the groups. RESULTS: Early after transplantation, there was no difference between the groups concerning fasting glucose, HbA1c levels, basal and stimulated insulin secretion, and incidence of normal glucose tolerance. Late after transplantation, the incidence of a normal glucose tolerance tended to be lower (70% vs. 78%), whereas HbA1c (5.3% vs. 5.0%) and fasting glucose (81 vs. 78 mg/dL) levels tended to be higher in tacrolimus-treated patients. However, these differences were not significant. Insulin secretion was not reduced in the tacrolimus group. CONCLUSIONS: Concerning glucose metabolism and secretory capacity of the pancreas graft, no significant differences were found comparing tacrolimus- versus cyclosporine-treated graft recipients.
