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PubMed1994

The frequency of rejection episodes after combined kidney-pancreas transplant--the impact on graft survival.

The recipients of combined kidney-pancreas transplants (SPK) are unique because they routinely receive two allografts from the same donor. In a previous study, we found that the long-term graft survival of the two allografts was different, with better graft survival seen in the pancreas allograft. In an attempt to understand the reason for the different graft survival in the recipients of organs from the same donor, we have reviewed the incidence and timing of rejection episodes in 160 consecutive technically successful whole-organ bladder-drained SPK performed at a single institution using a uniform immunosuppressive regimen. Rejection episodes were common. A total of 53% of the recipients had at least one episode of rejection in one of the organs. Multiple rejection episodes requiring hospitalization occurred in 23% of the recipients. The kidney allograft had more frequent rejection episodes than the pancreas allograft: 78 patients had 130 renal rejection episodes while only 50 patients had 65 episodes of pancreas rejection. No rejection episodes occurred in 111 pancreas and 82 kidney grafts (P = 0.0014). Multiple rejection episodes were three times as common in the kidney grafts (20%) than in the pancreas grafts (6%; P = 0.0001). The timing of the first rejection episode was also different. The median time to the first kidney rejection episode was 29 days compared with 39 days to the first pancreas rejection episode (P = 0.0191). Graft survival in the organs was equal when stratified by the number of rejection episodes (none, one, > one) per organ (P = 0.9378). These data suggest that the worse long-term kidney graft survival seen in SPK recipients is due to the greater risk of rejection (relative risk: 2.04; [95% conf. interval: 1.29-3.23]) and a greater frequency of rejection episodes of rejection episodes in the kidney (0.81/patient) compared with the pancreas (0.41/patient). The implications for patient management and the possible reasons for the different rates of rejection are discussed.

Adult↗
PubMed1997

Long-term renal function in type I diabetics after kidney or kidney-pancreas transplantation: influence of number, timing, and treatment of acute rejection episodes.

BACKGROUND: Previous studies comparing renal function in diabetic subjects receiving either a kidney or kidney-pancreas transplant generally have indicated no differences; however, these studies have been limited by inclusion of either a small number of patients or selected patients followed for relatively short periods of time. METHODS: To compare long-term renal function and factors affecting renal function in type I diabetic patients receiving either kidney or kidney-pancreas transplants, the slopes of regression lines generated by plotting the reciprocal of serum creatinine (1/Cr) versus time were measured in 109 consecutive patients followed for at least 12 and up to 102 months after transplantation. Multivariate analyses included linear regression using the slope of 1/Cr versus time as the dependent variable and logistic regression using a positive or negative slope as the dependent variable. RESULTS: Significant differences between kidney-pancreas (n=64) and kidney recipients (n=45) included a smaller proportion of African-Americans, lower rates of HLA matching, lower levels of panel-reactive antibodies, shorter cold ischemia times, a lower incidence of delayed graft function, and a higher incidence of acute renal allograft rejection episodes in the kidney-pancreas group. Trough cyclosporine blood levels were significantly higher in the kidney-pancreas group for the first 12 posttransplant months. The slopes of 1/Cr versus time were negative in each group with a trend toward a more negative slope in the kidney-pancreas group. Multivariate analyses indicated that a concomitant pancreas allograft did not influence long-term renal function. The total number of renal rejection episodes was the best independent predictor of a negative slope of 1/Cr versus time. However, use of OKT3 for the treatment of rejection within the first 3 months of transplantation exerted a surprisingly beneficial effect on long-term renal function, a phenomenon that was most apparent in the kidney-alone group. CONCLUSIONS: The frequency and timing of acute rejection episodes are more important than the influence of a simultaneously transplanted pancreatic allograft in determining long-term function of the transplanted kidney. A concerning trend toward late deterioration of renal function in kidney-pancreas recipients suggests that the benefits of sustained euglycemia, shorter cold ischemia times, lower rates of sensitization, and early use of OKT3 ultimately may be outweighed by the negative effects of more frequent renal rejection episodes.

Acute Disease↗
PubMed2000

Hypertension after pancreas-kidney transplantation: role of bladder versus enteric pancreatic drainage.

BACKGROUND: Recent reports suggest that hypertension may be less common after simultaneous pancreas-kidney transplantation than after kidney transplantation alone. However, the mechanisms for this beneficial effect have not been delineated. We hypothesize that lower blood pressures may result from chronic volume depletion in patients with bladder-drained pancreatic allografts. METHODS: We compared the incidence and severity of hypertension 12 months after transplantation in 79 bladder-drained pancreas-kidney recipients and 46 diabetic kidney-only recipients. These two groups were compared with a smaller group of enterically drained pancreas-kidney recipients. Blood pressure was also compared before and after surgical conversion from bladder to enteric drainage in 10 patients. RESULTS: Hypertension was significantly less common and less severe after pancreas-kidney transplantation than after kidney transplantation alone, but the benefit of the pancreas transplant was evident only in bladder-drained patients. Logistic regression analysis of the bladder-drained pancreas-kidney patients confirmed the independent impact of the pancreatic allograft on the presence of hypertension, indicated an independent association with serum creatinine concentration and donor age, but suggested no correlation with recipient age, race, or number of rejection episodes. A comparison of blood pressures before and after pancreatic conversion from bladder to enteric drainage indicated no significant change in the prevalence or severity of hypertension. CONCLUSIONS: We conclude that the beneficial effect of a pancreas transplant on the prevalence and severity of hypertension after simultaneous pancreas-kidney transplantation is limited to bladder-drained patients. Although it is possible that the effect is mediated by chronic volume depletion, the observation that blood pressure does not increase after conversion from bladder to enteric drainage suggests that other factors may be involved.

Adult↗
PubMed2003

Dialysis, kidney transplantation, or pancreas transplantation for patients with diabetes mellitus and renal failure: a decision analysis of treatment options.

Patients with type 1 diabetes mellitus and end-stage renal disease may remain on dialysis or undergo cadaveric kidney transplantation, living kidney transplantation, sequential pancreas after living kidney transplantation, or simultaneous pancreas-kidney transplantation. It is unclear which of these options is most effective. The objective of this study was to determine the optimal treatment strategy for type 1 diabetic patients with renal failure using a decision analytic Markov model. Input data were obtained from the published medical literature, the United Network for Organ Sharing registry, and patient interviews. The outcome measures were life expectancy (in life-years [LY]) and quality-adjusted life expectancy (in quality-adjusted life-years [QALY]). Living kidney transplantation was associated with 18.30 LY and 10.29 QALY; pancreas after kidney transplantation, 17.21 LY and 10.00 QALY; simultaneous pancreas-kidney transplantation, 15.74 LY and 9.09 QALY; cadaveric kidney transplantation, 11.44 LY and 6.53 QALY; dialysis, 7.82 LY and 4.52 QALY. The results were sensitive to the value of several key variables. Simultaneous pancreas-kidney transplantation had the greatest life expectancy and quality-adjusted life expectancy when living kidney transplantation was excluded from the analysis. These data indicate that living kidney transplantation is associated with the greatest life expectancy and quality-adjusted life expectancy for type 1 diabetic patients with renal failure. Treatment strategies involving pancreas transplantation should be considered for patients with frequent metabolic complications of diabetes and for those patients who favor kidney-pancreas transplantation over kidney transplantation alone. For patients without a living donor, simultaneous pancreas-kidney transplantation is associated with the greatest life expectancy.

Adult↗
PubMed2005

Internal hernia after pancreas transplantation with enteric drainage: an unusual cause of small bowel obstruction.

BACKGROUND: Although complications involving leaking at the enteric anastomosis site, graft thrombosis, and intraabdominal abscess formation have been well documented after pancreas transplantation, the occurrence of small bowel obstruction in this setting has received scant attention. Although uncommon, intestinal obstruction after pancreas transplantation may have atypical etiologies. In this article, we will review three unusual cases of intestinal obstruction in pancreas transplant recipients. The value of computed tomographic (CT) enteroclysis in equivocal situations in the diagnosis of the obstruction is emphasized. METHODS: In this study, we reviewed the posttransplant course of all pancreas transplants performed between July 1, 2002 and June 1, 2004. We specifically focused on all patients that required reexploration for suspected small bowel obstruction at any time after transplantation. RESULTS: A total of 65 pancreas transplants were performed between July 1, 2002 and June 1, 2004. Pancreas graft survival was 97%, and patient survival was 98.5%. Five (7.7%) patients presented with mechanical small bowel obstruction, three of which were secondary to internal herniation of small intestine through a defect posterior to the pancreas allograft. All patients recovered well postsurgically. DISCUSSION: Small bowel obstruction is an uncommon complication after pancreas transplantation. CT enteroclysis in the evaluation of small bowel obstruction may assist the patient care decision-making process by providing information on the location and severity of the obstruction in the clinical situation where conventional abdominal CT and radiography are equivocal. Prompt detection of small bowel obstruction with early surgical intervention can minimize complications and preserve allograft function.

Adult↗
PubMed1993

The size of the pancreas in diabetes mellitus.

To determine whether there was an association between the size of the pancreas and the type of diabetes, ultrasonography of the pancreas was performed on 57 diabetic patients: 14 with Type 1 (insulin-dependent) diabetes, 10 insulin-treated and 33 tablet-treated patients with Type 2 (non-insulin-dependent) diabetes, and 19 non-diabetic subjects. The pancreas of patients with Type 1 diabetes was markedly smaller (p < 0.0001) than the pancreas in non-diabetic subjects. The pancreas of patients with Type 2 diabetes was more moderate in size: larger (p < 0.001) than that of Type 1 diabetic patients but smaller (p < 0.5) than the pancreas of the control group. Pancreatic size of patients with Type 2 diabetes was also related to basal insulin secretion with insulin-deficient patients (low or undetectable C-peptide) having smaller (p < 0.05) pancreases than those with normal insulin secretion. There was no difference in the size of the pancreas in the different treatment groups of Type 2 diabetic patients. Pancreatic size did not correlate with age, body mass index or the duration of diabetes. We conclude that the pancreas is a smaller organ in patients with diabetes mellitus and that the decrement in size is maximal in insulin-dependent/insulin-deficient subjects. Ultrasonography, therefore, can potentially serve to discriminate between the different types of diabetes.

Adolescent↗
PubMed2004

Are criteria for islet and pancreas donors sufficiently different to minimize competition?

Islet and pancreas transplantation may compete for a limited number of organs. We analyzed records from the national Swiss transplant registry during a 4-year period to investigate the proportion of donors that are suitable for islet and pancreas transplantation. Suitability for pancreas transplantation was mainly defined as: age 10-45 years; weight <or= 80 kg; BMI <or= 25 kg/m(2); amylasemia <or= 150 U/l; ICU stay <or= 3 days and absence of severe hypotension (MAP <or= 60 mmHG). Between 1.1.1997 and 31.12.2000, data of 407 donors were collected, from which 321 donors were included in the study. Thirty-three (10%), 143 (45%), and 23 (7%) donors fulfilled the criteria for pancreas, islet transplantation, and both procedures, respectively. Giving priority to pancreas transplantation and accepting the absence of one selection criterion, 90 (28%) pancreas and 100 (31%) islet donors were identified. We conclude that with current allocation policies prioritizing pancreas transplantation, pancreas and islet transplantation may coexist with little competition.

Adult↗
PubMed1995

Uneven fatty replacement of the pancreas: evaluation with CT.

PURPOSE: To determine the computed tomographic (CT) features of uneven fatty replacement of the pancreas and clarify their radiologic and clinical importance. MATERIALS AND METHODS: CT scans from 80 patients with uneven fatty replacement of the pancreas were reviewed. Uneven fatty replacement of the pancreas was classified into two types. In type 1, the posterior aspect of the head of the pancreas was spared from intense fatty replacement. In type 2, the focal area around the common bile duct (CBD) was spared from fatty replacement. Each type was divided into two subgroups on the basis of whether the body and tail of the pancreas showed intense fatty replacement (type a = negative for intense fatty replacement, type b = positive for intense fatty replacement). Findings from endoscopic retrograde cholangiopancreatography performed in five patients, histopathologic examination in one patient, and clinical examination in all 80 patients were also evaluated. RESULTS: Twenty-eight patients (35%) had type 1a replacement, 29 (36%) had type 1b replacement, nine (11%) had type 2a replacement, and 14 (18%) had type 2b replacement. In all patients, the anterior aspect of the head of the pancreas showed distinctly lower attenuation at CT. CONCLUSION: Fatty replacement is more severe in the anterior aspect of the head of the pancreas. The posterior aspect of the head of the pancreas and the area around the CBD tended to be spared.

Adult↗
PubMed1993

The reduced canine pancreas to study the effects of intra-operative radiotherapy.

A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of the left and right lobes of the pancreas facilitates the delivery of IORT, reduces the risk of pancreatitis and will demonstrate, eventually, minimal functional changes in the exocrine and endocrine pancreas at an earlier stage. Sixteen beagles were used. Investigations before and after the reduction procedure were intravenous glucose tolerance tests, serum insulin levels, faecal fat excretion, blood chemistry tests and body weight. Eight weeks after the pancreas reduction 15 dogs underwent an IORT procedure in which 25, 30 or 35 Gy IORT was delivered to the pancreatic remnant. We conclude that the pancreas reduction technique used to study the effects of IORT to the canine pancreas is feasible without mortality or morbidity. Endocrine and exocrine pancreatic function remained normal with a minimal follow-up of 3 months.

Animals↗
PubMed2001

Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation.

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.

Acute Disease↗
PubMed1992

Release of peptide-YY from the dog pancreas.

The objectives of this study were to characterize the distribution of immunoreactive peptide-YY (PYY) in the dog pancreas and to examine whether vagal stimulation can release PYY from the pancreas. Levels of pancreatic polypeptide (PP) were also measured. PYY levels in extracts of the right lobe (0.43 +/- 0.03 ng/mg tissue) and head (0.35 +/- 0.12 ng/mg tissue) of the pancreas were approximately 10- to 20-fold higher than those in extracts of the stomach (0.03 +/- 0.01 ng/mg tissue; P less than 0.05) and left lobe of the pancreas (0.02 +/- 0.01 ng/mg tissue). However, PYY levels in extracts of the pancreas and stomach were significantly lower than PYY levels in extracts of the colonic mucosa (7.63 +/- 0.71 ng/mg tissue). PP levels were significantly (300-fold) higher in pancreatic extracts than in stomach and colonic extracts. Immunoreactive PYY and PP in pancreatic and colonic mucosal extracts coeluted with synthetic PYY and PP standards on HPLC. Electrical vagal stimulation of dogs resulted in a significant (P less than 0.05) release of PYY and PP, which was abolished by atropine treatment (2 mg/kg, iv). PYY levels in the pancreatic veins increased more quickly than in the peripheral veins. The integrated levels of PYY in the pancreatic veins [1.63 +/- 0.30 ng (0-30 min)/ml] were significantly (P less than 0.05) higher than those in peripheral veins [0.86 +/- 0.16 ng (0-30 min)/ml], but lower than those in colonic veins [3.14 +/- 0.22 ng (0-30 min)/ml]. Our results indicate that PYY is primarily produced in the colon; however, the pancreas contains a measurable amount of PYY, which is mainly distributed in the right lobe and head of the pancreas. In addition, PYY can be released from the pancreas in response to vagal stimulation. These data suggest that pancreatic PYY may participate in the regulation of pancreatic and gastrointestinal functions through endocrine and paracrine actions.

Animals↗
PubMedDate not supplied

Pancreas transplantation.

Although intensified insulin therapy regimens enable normalization of blood glucose levels and related metabolic parameters, these regimens are associated with an increased incidence of hypoglycemic episodes. Pancreas transplantation has achieved the goal of providing insulin independence with stable and continuous normoglycemia. But because of the associated morbidity and mortality and the need for life-long immunosuppression after transplant, it is difficult to justify pancreas transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation is therefore performed in conjugation with renal transplantation. The majority of renal transplant centers, however, have been reluctant to perform simultaneous kidney-pancreas transplantation in insulin-dependent uremic patients because of the additional risks associated with pancreas transplantation. More recently, refinements in surgical technique, introduction of new immunosuppressive agents, and better selection of transplant candidates have contributed to improved survival. Today, combined pancreas-kidney transplantation is an accepted treatment for carefully selected patients with insulin dependent diabetes and end-stage renal disease and in a small group of patients with uncontrolled severe metabolic problems. The effect of a euglycemic state after pancreas transplantation on the progression of micro- and macroangiopathy remains to be proved, although recently there is evidence to suggest that some end-organ lesions may be halted or even ameliorated. Further improvement in anti-rejection strategies may achieve better long-term graft survival and provide the incentive to perform pancreas transplantation at an earlier stage, before severe secondary complications of diabetes develop.

Adult↗
PubMed1976

Adrenaline in the human pancreas.

The present study describes the results of examinations of the noradrenaline and adrenaline concentrations in the human pancreas as well as in a number of other organs. Tissue specimens were obtained at post-mortem examination. Adrenaline was present in small amounts in the cardiovascular system, the liver and the spleen in comparison with the noradrenaline concentration. The pancreas, especially the body of the pancreas, contained, however, considerable amounts of adrenaline. The average adrenaline concentration was approximately 20 times higher in the pancreas than in the other organs examined. The greatest concentration of adrenaline was found in the posterior and superior parts of the body of the pancreas. There was no relationship between the cause of death in the human subjects and the adrenaline concentration in the pancreas and large amounts of adrenaline were also found in tissue specimens of pancreas obtained from long-term diabetic patients. Adrenaline was present in the pancreas of the rat, dog and rabbit but in small amounts in comparison with the noradrenaline concentration.

Adult↗
PubMed1983

Pancreatic polypeptide and insulin contents in diabetic and nondiabetic human pancreas and their relationship to the stability of the fasting serum glucose.

The amounts of insulin and pancreatic polypeptide (PP) in twenty four autopsied diabetic and nineteen nondiabetic human pancreases were determined and their relationship to the stability of the fasting serum glucose level was investigated. The PP content of the tail of the pancreas in diabetic and nondiabetic subjects was 9.55 +/- 2.41 and 7.71 +/- 1.52 micrograms/g pancreas, and that of the head of the pancreas was 16.86 +/- 5.51 and 15.82 +/- 5.38 micrograms/g, respectively. No significant differences in content were found between diabetic and nondiabetic pancreases. The PP content of the head pancreas of some diabetics and nondiabetics was higher than that of the tail. The insulin content of the tail of the diabetic pancreas was lower than that of the nondiabetic pancreas. In those diabetics where there was less than 0.5 U/g of insulin in the tail pancreas, the stability of the fasting serum glucose was very poor, indicating an unstable type of diabetes. There was a significant inverse correlation between standard deviation of FBS and the amount of insulin, but the PP content of the pancreas had no relation to the stability of the fasting serum glucose.

Adult↗
PubMed1995

The incidence of interstitial and vascular kidney rejection after pancreas-kidney transplantation.

Several groups have reported that recipients of a simultaneous pancreas-kidney transplantation suffer from more kidney rejection episodes than do recipients of a kidney transplantation (1-6). However, it is not known whether this is interstitial rejection, vascular rejection, or both. In this study, the renal biopsies and transplantectomies of 45 pancreas-kidney and 48 kidney transplant recipients were evaluated for the presence of interstitial and vascular rejection. Furthermore, the influence of OKT3 induction therapy on rejection after pancreas-kidney transplantation was studied. Of the 45 pancreas-kidney recipients. 4 patients did not suffer from rejection during follow-up, 28 suffered only from interstitial rejection, and 13 suffered from vascular (with or without interstitial) rejection, whereas 12, 19, and 14 of the 48 kidney transplant patients had no rejection, interstitial rejection, or vascular (with or without interstitial) rejection, respectively. Three patients with a kidney transplant were treated for rejection although no biopsy was taken. In the pancreas-kidney group, 38 of the total of 149 biopsies and transplantectomies taken contained no rejection, 92 had interstitial rejection, and 19 had vascular rejection. In the kidney group, these values were 13, 41, and 25, respectively, of 79 biopsies and transplantectomies taken (P = 0.002). Five-year renal graft survival was 79% in the kidney group and 60% in the pancreas-kidney group. Renal graft survival rates differed significantly (P = 0.02). Renal graft survival and occurrence of rejection did not reach significance between pancreas-kidney recipients treated with OKT3 induction therapy and pancreas-kidney recipients receiving conventional triple therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pancreas-transplant outcome in relation to presence or absence of end-stage renal disease, timing of transplant, surgical technique, and donor source.

The differences in pancreas-transplant outcome according to recipient status, surgical approach, and donor source are illustrated by an analysis of results at one institution with experience in several categories. From July 1978 to January 1988, 210 pancreas transplants were performed, and 67 grafts are still functioning, the longest for 9.7 yr. Since October 1984, a uniform immunosuppressive protocol has been used, antilymphocyte globulin, cyclosporin, azathioprine, and prednisone for induction and the last three drugs for maintaining antirejection therapy. During this period, 110 pancreas transplants were performed, 62 in nonuremic non-kidney transplants, 28 in recipients of a previous kidney, and 20 simultaneous with a kidney; 64 with bladder and 43 with enteric drainage; and 25 from related and 85 from cadaver donors. The overall patient survival rate at 1 yr was 91%, and there were no significant differences between the various categories. Graft survival rates, however, differed between the various categories created by combinations of the above variables. With bladder drainage, 1-yr function rates were 58% (n = 30), 47% (n = 15), and 77% (n = 19) in recipients of a pancreas transplant alone, a pancreas after a kidney, or a simultaneous pancreas-kidney transplant; with enteric drainage, 1-yr function rates were 33% (n = 32) and 36% (n = 11) in the pancreas transplant alone and pancreas after kidney categories (enteric drainage was not done in double-transplant patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1996

Hepatic insulin resistance after pancreas transplantation in type I diabetes.

Hyperinsulinemia and peripheral insulin resistance caused by systemic insulin delivery and prednisone therapy are recognized consequences of pancreas transplantation. However, there is little information about insulin action on the liver. To investigate hepatic insulin sensitivity in recipients of pancreas transplants, we devised a staged euglycemic hyperinsulinemic clamp to measure hepatic glucose production (HGP) in 10 type I diabetic pancreas transplant recipients, 10 pair-matched healthy control subjects, and 6 nondiabetic kidney transplant recipients. Clamps were performed in two sequential stages. In stage 1, a 2-h low-dose insulin infusion (0.4 mU.kg-1.min-1) was used to partially suppress HGP. In stage 2, insulin-mediated suppression of HGP was challenged by a 1.5-h glucagon infusion (0.8 ng.kg-1.min-1), while continuing the hyperinsulinemic euglycemic-clamp conditions. During both stages, somatostatin (250 micrograms/h) was infused to suppress endogenous insulin secretion. All subjects underwent stage 1, and all except one pancreas recipient and a respective matched healthy control subject completed stage 2. Fasting HGP was greater in pancreas recipients than in healthy control subjects (15.1 +/- 0.7 vs. 12.0 +/- 0.4 mumol.l-1.kg-1.min-1, P < 0.005) but similar in healthy control subjects and in kidney recipients. During stage 2, both total (706 +/- 28 vs. 469 +/- 31 mumol.l-1.kg-1, P < 0.005) and incremental (62 +/- 20 vs. -21 +/- 16 mumol.l-1.kg-1, P < 0.005) HGP responses to glucagon infusion were significantly greater in pancreas recipients than in healthy control subjects. Changes in HGP in kidney recipients during stage 2 were not significantly different from those in healthy control subjects. In conclusion, fasting HGP is increased in pancreas transplant recipients. Furthermore, recipients have hepatic insulin resistance as demonstrated by an enhanced stimulatory effect of glucagon on HGP during insulin-mediated HGP suppression. Because the magnitude of hepatic insulin resistance was a significant (P < 0.01) predictor of HbA1c level, we suggest that variable hepatic insulin resistance may be responsible for some of the variance observed in glycemic levels after successful pancreas transplantation.

Adult↗
PubMed1998

Hypoglycemia after pancreas transplantation.

OBJECTIVE: Hypoglycemia is a serious complication of therapy for diabetes. Chronic hypoglycemia and the attendant decrease in quality of life have been rationales for advocating pancreas transplantation as an alternative treatment. However, reports have appeared that suggest that as high as 30-50% of pancreas transplant recipients have occasional symptoms of mild hypoglycemia. Therefore, we studied glucose and hormone levels in transplant recipients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied glucose and hormone levels in transplant recipients reporting frequent symptoms of hypoglycemia (n = 10), transplant recipients without symptoms of hypoglycemia (n = 9), and healthy control subjects (n = 8) after a mixed meal and during a subsequent 24-h modified fast. All transplant recipients were insulin-independent; were receiving prednisone, cyclosporine, and azothioprine; and had functioning grafts with systemic venous drainage. RESULTS: No significant differences were observed in the fasting glucose, insulin, C-peptide, or glucagon levels when comparing the symptomatic with the asymptomatic groups of patients who had undergone successful pancreas transplantation. Similarly, no significant differences were found in the immediate postprandial period after a mixed meal. However, during the subsequent 24-h fast, glucose levels fell lower in the symptomatic than in the asymptomatic group of patients receiving a transplanted pancreas (71+/-2 vs. 81+/-2 mg/dl, P < 0.002). During the fast, no significant differences were found in insulin, C-peptide, or glucagon levels when comparing asymptomatic to symptomatic groups. Of 10 symptomatic recipients of pancreas transplantation, 5 reported symptoms of hypoglycemia during the study. In four of these five subjects, the onset of symptoms corresponded to nadirs in serum glucose, which occurred at values 2 SD or more below the mean glucose observed for the control and the asymptomatic pancreas recipient groups. The serum glucose levels at the time of symptoms in these four subjects were 55, 66, 51, and 57 mg/dl. In each of these four subjects, symptoms abated and the glucose levels rose spontaneously without intervention. One of these four subjects had elevated insulin binding activity in his serum consistent with endogenous insulin antibodies. This individual had a serum glucose value of 55 mg/dl at the conclusion of the 24-h fast without symptoms. CONCLUSIONS: Among a group of pancreas transplant recipients reporting frequent symptoms of hypoglycemia, some individuals demonstrated transient, symptomatic postprandial hypoglycernia. With the exception of one recipient with insulin antibodies, no evidence was found for hypoglycemia during fasting. Although postprandial hypoglycemia may occur in some pancreas transplant recipients, it does not appear to be a highly significant clinical problem.

Activities of Daily Living↗