c-peptide and Postoperative-Complications

Topics: Adult; Animals; C-Peptide; Carbohydrate Metabolism; Cattle; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Dogs; Graft Survival; Humans; Immunosuppression Therapy; Islets of Langerhans Transplantation; Kidney Transplantation; Middle Aged; Pancreas; Pancreas Transplantation; Pancreatic Ducts; Postoperative Complications; Stomach; Vasculitis

One year survival of islet cell grafts has been reproducibly achieved under combination immune therapy including tacrolimus (TAC). However, the use of TAC causes beta-cell and renal toxicity. Because sirolimus (SIR) monotherapy was successful in kidney transplantation under antithymocyte globulin (ATG), we undertook a pilot study comparing SIR monotherapy with SIR-TAC combination therapy.. Nonuremic type 1 diabetics received a cultured beta-cell graft under ATG and were randomly assigned to SIR or SIR-TAC-maintenance therapy; a second graft was implanted during posttransplantation month 3 without ATG. The planned number of patients per group (n=10) was reduced to five in view of the observed side effects.. At posttransplant month 6, three SIR-patients had lost graft function and two presented marginal function; among SIR-TAC-patients, there were two early graft failures but three became insulin-independent. These three patients maintained metabolically relevant function (C-peptide >1 ng/ml and coefficient of variation fasting glycemia <25%) for more than 2 years but low-dose insulin therapy was needed from 8, 18, and 26 months posttransplant; this was still the case in two of them after reducing and stopping TAC dose. In both groups, incapacitating adverse events were attributed to sirolimus requiring its discontinuation in 4 of 10 patients; in the 3 patients with pretransplant microalbuminuria, macroalbuminuria developed which resolved when sirolimus was stopped.. SIR monotherapy is not sufficient to suppress rejection after transplantation under ATG, but it can maintain survival of established beta-cell grafts. However, the risk for a SIR-induced proteinuria remains a concern.

Topics: Adult; Albuminuria; Autoantibodies; C-Peptide; Cell Transplantation; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Graft Survival; Humans; Immunosuppressive Agents; Islets of Langerhans; Islets of Langerhans Transplantation; Lymphocyte Count; Male; Middle Aged; Postoperative Complications; Sirolimus; Tacrolimus

Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients.. We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group).. GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 +/- 3.5% at baseline to 74.9 +/- 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 +/- 0.25 to 4.20 +/- 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 +/- 4.9 to 44.6 +/- 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 +/- 8.3 to 57.2 +/- 4.6 ms, P < 0.05) with higher erythrocytes Na(+)-K(+)-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness.. Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Topics: Atrial Natriuretic Factor; C-Peptide; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Erythrocytes; Female; Graft Survival; Humans; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Sodium-Potassium-Exchanging ATPase

To assess the safety and efficacy of islet autotransplantation (IAT) combined with total pancreatectomy (TP) to prevent diabetes.. There have been recent concerns regarding the safety of TP and IAT. This is thought to be related to the infusion of large volumes of unpurified pancreatic digest into the portal vein. Minimizing the volume of islet tissue by purifying the pancreatic digest has not been previously evaluated in terms of the postoperative rate of death and complications, pain relief, and insulin independence.. During a 54-month period, 24 patients underwent pancreas resection with IAT. Islets were isolated using collagenase and a semiautomated method of pancreas digestion. Where possible, islets were purified on a density gradient and COBE processor. Islets were embolized into the portal vein, within the spleen and portal vein, or within the spleen alone. The total median volume of digest was 9.9 mL.. The median number of islets transplanted was 140,419 international islet equivalents per kilogram. The median increase in portal pressure was 8 mmHg. Early complications included duodenal ischemia, a wedge splenic infarct, partial portal vein thrombosis, and splenic vein thrombosis. Intraabdominal adhesions were the main source of long-term problems. Eight patients developed transient insulin independence. Three patients were insulin-independent as of this writing. Patients had significantly decreased insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. Of the patients alive and well as of this writing, four had failed to gain relief of their abdominal pain and were still opiate-dependent.. Combined TP and IAT can be a safe surgical procedure. Unfortunately, almost all patients were still insulin-dependent, but they had decreased daily insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. A prospective randomized study is therefore needed to assess the long-term benefit of TP and IAT on diabetic complications.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; England; Female; Humans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Pancreatitis; Postoperative Complications; Prospective Studies; Statistics, Nonparametric

After surgical trauma, protein synthesis, as well as the concentration of free glutamine in muscle, decreases. Total parenteral nutrition (TPN) alone does not prevent the decrease of glutamine in muscle, but TPN supplemented with glutamine or its precursor, alpha-ketoglutarate, maintains amino acid concentration in muscle and preserves protein synthesis. The aim of this study was to characterize a human trauma model using patients undergoing total hip replacement, and furthermore to investigate whether glutamine or alpha-ketoglutarate alone without TPN can prevent the postoperative decrease in muscle free glutamine. Metabolically healthy patients undergoing total hip replacement were randomized into three groups. The control group (n = 13) received glucose 2 g/kg body weight (BW) during surgery and the first 24 postoperative hours. The glutamine group (n = 10) received glucose 2 g/kg BW and glutamine 0.28 g/kg BW, and the alpha-ketoglutarate group (n = 10) received glucose 2 g/kg BW and alpha-ketoglutarate 0.28 g/kg BW. Muscle biopsies were performed before surgery and 24 hours postoperatively. Free glutamine concentration in muscle decreased from 11.62 +/- 0.67 to 9.80 +/- 0.36 mmol/kg wet weight in the control group (P < .01), whereas it remained unchanged in both the glutamine group and alpha-ketoglutarate group. Protein synthesis, as reflected by the concentration of total ribosomes, decreased significantly in the control group, but not in glutamine and alpha-ketoglutarate groups. Polyribosome concentration decreased significantly in both the control and alpha-ketoglutarate groups. Total hip replacement can be used as a reproducible trauma model, with characteristic changes in the muscle amino acid pattern and protein synthesis 24 hours postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acids; Blood Glucose; C-Peptide; Glucagon; Glutamine; Hip Prosthesis; Humans; Hydrocortisone; Insulin; Ketoglutaric Acids; Muscles; Parenteral Nutrition, Total; Postoperative Complications; Protein Biosynthesis; Ribosomes

Topics: Antilymphocyte Serum; Azathioprine; C-Peptide; Cells, Cultured; Cyclosporine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Immunosuppression Therapy; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Muromonab-CD3; Postoperative Complications; Prednisone; Tissue Preservation; Transplantation, Heterotopic; Transplantation, Homologous

Therapeutic pancreatic duct occlusion (PDO) is applied to preserve endocrine pancreatic function by atrophizing and thus eliminating chronically inflamed exocrine pancreatic parenchyma. So far, efficient and lasting elimination of exocrine parenchyma is brought about only by intraoperative PDO upon partial duodenopancreatectomy. While partial duodenopancreatectomy itself reduces endocrine pancreatic function by about 40%, intraoperative PDO does not further impair endocrine function. Endocrine function is not affected at all by endoscopic PDO, which has to be improved, however, concerning its eliminatory effect on exocrine pancreatic parenchyma.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diatrizoate; Drug Combinations; Endoscopy; Fatty Acids; Follow-Up Studies; Humans; Insulin; Isoamylase; Lipase; Pancreatectomy; Pancreatic Ducts; Pancreatic Function Tests; Pancreatic Pseudocyst; Pancreatitis; Postoperative Complications; Propylene Glycols; Proteins; Trypsin; Zein

This study aimed to identify the clinical factors affecting postoperative residual pancreatic β-cell function, as assessed by the C-peptide index (CPI), and to investigate the association between perioperative CPI and the status of diabetes management after pancreatectomy.. The associations between perioperative CPI and clinical background, including surgical procedures of pancreatectomy, were analyzed in 47 patients who underwent pancreatectomy, and were assessed for pre-and postoperative CPI. The association between perioperative CPI and glycemic control after pancreatectomy was investigated.. The low postoperative CPI group (CPI <0.7) had longer duration of diabetes (17.5 ± 14.5 vs 5.5 ± 11.0 years, P = 0.004), a higher percentage of sulfonylurea users (41.7 vs 8.7%, P = 0.003) and a greater number of drug categories used for diabetes treatment (1.9 ± 1.1 vs 0.8 ± 0.8, P <0.001) than did the high postoperative CPI group. Postoperative CPI was higher (1.4 ± 1.2 vs 0.7 ± 0.6, P = 0.039) in patients with low glycosylated hemoglobin (<7.0%) at 6 months after pancreatectomy; preoperative (2.0 ± 1.5 vs 0.7 ± 0.5, P = 0.012) and postoperative CPI (2.5 ± 1.4 vs 1.4 ± 1.1, P = 0.020) were higher in non-insulin users than in insulin users at 6 months after surgery.. The duration of diabetes and preoperative diabetes treatment were associated with residual pancreatic β-cell function after pancreatectomy. Furthermore, perioperative β-cell function as assessed by CPI was associated with diabetes management status after pancreatectomy.

Topics: C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; Humans; Pancreatectomy; Postoperative Complications; Retrospective Studies

Decreased pancreatic volume (PV) is a predictive factor for diabetes mellitus (DM) after surgery. There are few reports on PV and endocrine function pre- and post-surgery. We investigated the correlation between PV and insulin secretion.. Seventeen patients underwent pancreaticoduodenectomy (PD) Pre- and post-surgery PV and C-peptide index (CPI) measurements were performed. Additionally, the correlation between PV and CPI was analyzed.. The mean preoperative PV (PPV) was 55.1 ± 31.6 mL, postoperative remnant PV (RPV) was 25.3±17.3 mL, and PV reduction was 53%. The mean preoperative C-peptide immunoreactivity (CPR) was 1.39 ± .51 and postoperative CPR was .85±.51. The mean preoperative CPI was 1.29±.72 and postoperative CPI was .73 ± .48. Significant correlations were observed between RPV and post CPR (ρ = .507, P = .03) and post CPI (ρ = .619, P = .008).. There was a significant correlation between RPV and CPI after PD. A smaller RPV resulted in lower insulin secretion ability, increasing the potential risk of new-onset DM after PD.

Topics: Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Male; Multidetector Computed Tomography; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Retrospective Studies

BACKGROUND The main purpose of diagnostic imaging after pancreas transplantation is to exclude potential complications. As long as standard anatomical imaging such as sonography, contrast-enhanced computed tomography, and magnetic resonance imaging (MRI) are sufficient to display macroscopic vasculature, early changes within the graft caused by insufficient microperfusion will not be displayed for evaluation. MATERIAL AND METHODS Patients with pancreas allograft function in good condition were included in the study. No specific preparation was demanded before the MRI examination. The results of MRI were correlated with Igls criteria. It was a preliminary study to examine diffusion tensor imaging (DTI) value and safety in pancreas transplantation. RESULTS Our results indicated that higher fractional anisotropy (FA) values of the graft's head were associated with delayed graft function and insulin intake. We also compared grafts' images in early and late periods and found differences in T1 signal intensity values. DTI is a reliable noninvasive tool, requiring no contrast agent, to assess graft microstructure in correlation with its function, with FA values showing the most consistent results. By Igls criteria, no graft failure, 76% had optimal function, 10% had good function, and 14% had marginal function. CONCLUSIONS Our results suggest that DTI can be safely used in patients after pancreas transplantation and is advantageous in detecting early as well as late postoperative complications such as intra-abdominal fluid collection, malperfusion, and ischemia of the graft. Our findings correspond with clinical condition and Igls criteria. DTI is free of ionizing agents and is safe for kidney grafts.

Topics: Adult; Allografts; Anisotropy; C-Peptide; Contrast Media; Delayed Graft Function; Diffusion Tensor Imaging; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin-Secreting Cells; Ischemia; Male; Pancreas Transplantation; Postoperative Complications; Prospective Studies; Transplantation, Homologous; Treatment Outcome

High-quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet-enriched microRNAs (miRNAs) -375 and -200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR-375, miR-200c, and C-peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C-peptide, hemoglobin A

Topics: Adult; Blood Glucose; C-Peptide; Cell Separation; Diabetes Mellitus, Type 1; Endocrine System; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; MicroRNAs; Postoperative Complications; Risk Factors; Transplantation, Autologous; Treatment Outcome

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients.. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events.. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment.. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

Topics: Adult; Antilymphocyte Serum; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Islets of Langerhans Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Risk Assessment; Risk Factors; Tacrolimus; Time Factors; Transplantation, Homologous; Treatment Outcome

Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation.. We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant.. Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.. At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Topics: Acute Disease; Adult; C-Peptide; Cohort Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Health Facilities; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Postoperative Complications; Recurrence; Retrospective Studies; Transplantation, Autologous; Treatment Outcome

Islet autotransplant (IAT) may ameliorate postsurgical diabetes following total pancreatectomy (TP), but outcomes are dependent upon islet mass, which is unknown prior to pancreatectomy. We evaluated whether preoperative metabolic testing could predict islet isolation outcomes and thus improve assessment of TPIAT candidates. We examined the relationship between measures from frequent sample IV glucose tolerance tests (FSIVGTT) and mixed meal tolerance tests (MMTT) and islet mass in 60 adult patients, with multivariate logistic regression modeling to identify predictors of islet mass ≥2500 IEQ/kg. The acute C-peptide response to glucose (ACRglu) and disposition index from FSIVGTT correlated modestly with the islet equivalents per kilogram body weight (IEQ/kg). Fasting and MMTT glucose levels and HbA1c correlated inversely with IEQ/kg (r values -0.33 to -0.40, p ≤ 0.05). In multivariate logistic regression modeling, normal fasting glucose (<100 mg/dL) and stimulated C-peptide on MMTT ≥4 ng/mL were associated with greater odds of receiving an islet mass ≥2500 IEQ/kg (OR 0.93 for fasting glucose, CI 0.87-1.0; OR 7.9 for C-peptide, CI 1.75-35.6). In conclusion, parameters obtained from FSIVGTT correlate modestly with islet isolation outcomes. Stimulated C-peptide ≥4 ng/mL on MMTT conveyed eight times the odds of receiving ≥2500 IEQ/kg, a threshold associated with reasonable metabolic control postoperatively.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis, Chronic; Postoperative Complications; Preoperative Care; Prognosis; Prospective Studies; Risk Factors; Transplantation, Autologous

Over a 23-year period, our center performed 82 renal retransplants in prior simultaneous pancreas-kidney recipients with functioning pancreatic allografts. All patients were insulin-independent at retransplantation. We aimed to quantify the risk of returning to insulin therapy and to identify factors that predispose patients to pancreatic allograft failure after renal retransplantation. Among these 82 patients, pancreatic allograft survival after renal retransplantation was 78%, 49% and 40% at 1, 5 and 10 years. When analyzing risk factors, we unexpectedly found no clear relationship between the cause of primary renal allograft failure, hemoglobin A1c (HbA1c) or fasting C-peptide level at retransplant and subsequent pancreatic allograft failure. An elevated HbA1c in the month after renal retransplant correlated with subsequent pancreatic graft loss and patients experiencing pancreatic graft loss were more likely to subsequently lose their renal retransplant. Although it is difficult to prospectively identify those patients who will return to insulin therapy after repeat renal transplantation, the relatively high frequency of this event mandates that this risk be conveyed to patients. Nonetheless, the survival benefit associated with renal retransplantation justifies pursuing retransplantation in this population.

Topics: Adult; C-Peptide; Diabetic Nephropathies; Female; Follow-Up Studies; Glycated Hemoglobin; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Reoperation; Retrospective Studies; Risk Factors; Survival Rate; Transplantation, Homologous

The objective of this study was to identify predictors of insulin independence and to establish the best clinical tools to follow patients after pancreatic islet transplantation (PIT). Sequential metabolic responses to intravenous (I.V.) glucose (I.V. glucose tolerance test [IVGTT]), arginine and glucose-potentiated arginine (glucose-potentiated arginine-induced insulin secretion [GPAIS]) were obtained from 30 patients. We determined the correlation between transplanted islet mass and islet engraftment and tested the ability of each assay to predict return to exogenous insulin therapy. We found transplanted islet mass within an average of 16 709 islet equivalents per kg body weight (IEQ/kg BW; range between 6602 and 29 614 IEQ/kg BW) to be a poor predictor of insulin independence at 1 year, having a poor correlation between transplanted islet mass and islet engraftment. Acute insulin response to IVGTT (AIR(GLU) ) and GPAIS (AIR(max) ) were the most accurate methods to determine suboptimal islet mass engraftment. AIR(GLU) performed 3 months after transplant also proved to be a robust early metabolic marker to predict return to insulin therapy and its value was positively correlated with duration of insulin independence. In conclusion, AIR(GLU) is an early metabolic assay capable of anticipating loss of insulin independence at 1 year in T1D patients undergoing PIT and constitutes a valuable, simple and reliable method to follow patients after transplant.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucose Tolerance Test; Graft Rejection; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Postoperative Complications; Transplantation, Homologous; Young Adult

Periampullary malignant neoplasms have been increasing in Japan, mainly in response to an increase in the incidences of pancreatic cancer, and glucose intolerance due to deterioration of insulin secretion is an important problem. We investigated preoperative parameters to predict postoperative insulin secretion and the need for insulin therapy in patients undergoing pancreaticoduodenectomy (PD). Thirty-six patients with malignant neoplasms of periampullary lesions were enrolled. Preoperative pancreatic parenchymal thickness was evaluated by computed tomography. Insulin secretion and glucose tolerance were evaluated by a 75-g oral glucose tolerance test and an intravenous glucagon loading test. The relationships between postoperative insulin secretion and preoperative parameters and the cut-off values for predicting the need for postoperative insulin therapy for glycemic control were investigated. Pancreatic parenchymal thickness and other preoperative parameters, including the increment of serum C-peptide (Δ C-peptide), fasting plasma C-peptide (F-CPR), insulinogenic index (I.I.) and fasting plasma glucose (FPG), were significantly associated with postoperative insulin secretion. Multiple regression analyses revealed that preoperative Δ C-peptide or F-CPR was the most significant determinant of postoperative insulin secretion, followed by pancreatic parenchymal thickness. In the receiver operating characteristic curve, the best preoperative cut-off values for predicting the need for postoperative insulin therapy were a Δ C-peptide of 0.65 ng/mL, a F-CPR of 0.85 ng/mL and a pancreatic parenchymal thickness of 6.0 mm. Both preoperative insulin secretion and pancreatic parenchymal thickness effectively predict postoperative insulin secretion and identify subjects who need postoperative insulin therapy for glycemic control.

Topics: Abdominal Neoplasms; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Organ Sparing Treatments; Pancreas; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Prognosis; ROC Curve; Tomography, X-Ray Computed

Tight glucose control (TGC) using a sliding scale based on intermittent blood glucose measurements occasionally can have a fatal outcome as a result of insulin-induced hypoglycemia. The present study was undertaken to examine whether the use of an artificial pancreas to achieve TGC would be possible in postoperative patients with sepsis. The retrospective study was carried out as an exploratory study, focusing on the possibility of precise evaluation of the significance of TGC as a beneficial intervention by serological monitoring of various mediators. TGC was accomplished using an artificial pancreas (STG-22; (Nikkiso, Tokyo, Japan). The patients were divided into two groups: the TGC group (6 patients with sepsis in whom the target blood glucose level set at <150 mg/dl was attempted using the artificial pancreas), and the glucose control (GC) group (6 patients with sepsis in whom glucose control was attempted using a sliding scale; target blood glucose level was set at 200 mg/dl or lower). The mean blood glucose level was 129.7 ± 9.7 mg/dl in the TGC group and 200.9 ± 14.7 mg/dl in the GC group (P < 0.01, ANOVA). No hypoglycemia associated with the artificial pancreas was seen in any of the patients. The serum levels of S100A12 and HMGB-1 tended to decrease, and those of sRAGE tended to increase, in the TGC group. Further data collection from a larger number of cases would be expected to allow a precise assessment of TGC as a potentially beneficial intervention in sepsis patients.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Blood Glucose; C-Peptide; C-Reactive Protein; Cohort Studies; Cytokines; Energy Intake; Female; Glycation End Products, Advanced; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Pancreas, Artificial; Postoperative Complications; Respiration, Artificial; Retrospective Studies; Sepsis

The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.. Seventeen islet transplant recipients underwent SIIs after developing graft dysfunction requiring insulin use. For induction therapy, four subjects received daclizumab induction therapy, whereas 13 subjects received thymoglobulin and etanercept. Maintenance immunosuppression consisted of sirolimus+tacrolimus or tacrolimus+cellcept.. SII was performed 49.3+/-4.8 months (mean+/-SEM) after the preceding islet transplant. Subjects received significantly lower islet mass with their SII compared with initial transplant(s) (6076+/-492 vs. 9071+/-796 IEQ/kg; P=0.003). Fifteen of the 17 subjects (88.2%) became insulin independent 2.4+/-0.5 months after SII. Insulin-independent duration after SII exceeded that of the initial transplant(s) (24.8+/-2.2 vs. 14.2+/-2.6 months by Kaplan-Meier analysis, P=0.009). Subjects show improved glycemic control after SII (HbA1c 7.0%+/-0.2% pre-SII vs. 6.1%+/-0.2% post-SII, P=0.005) and did not become immunosensitized.. Using current protocols, SII in the absence of exenatide results in impressive insulin-independence rates and the durability of insulin independence seems to be promising. However, a beneficial effect of exenatide should not be discounted until tested in randomized controlled studies.

Topics: Antilymphocyte Serum; Blood Glucose; C-Peptide; Drug Therapy, Combination; Etanercept; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Immunoglobulin G; Immunosuppressive Agents; Insulin; Islets of Langerhans Transplantation; Male; Postoperative Complications; Receptors, Tumor Necrosis Factor; Sirolimus; Tacrolimus

Islet transplantation can restore normoglycemia to patients with unstable type 1 diabetes mellitus, but long-term insulin independence is usually not sustained. Identification of predictor(s) of islet allograft dysfunction (IGD) might allow for early intervention(s) to preserve functional islet mass.. Fourteen islet transplantation recipients with long-term history of type 1 diabetes mellitus underwent metabolic testing by mixed meal tolerance test, intravenous glucose tolerance test, and arginine stimulation test every 3 months postislet transplant completion. Metabolic responses were compared between subjects who maintained insulin independence at 18 months (group 1; n=5) and those who restarted insulin within 18 months (group 2; n=9). Data were analyzed before development of islet graft dysfunction and while insulin independent.. The 90-min glucose, time-to-peak C-peptide, and area under the curve for glucose were consistently higher in group 2 and increased as a function of time. At 12 months, acute insulin release to glucose in group 2 was markedly reduced as compared with baseline (5.62+/-1.21 microIU/mL, n=4 vs. 16.14+/-3.69 microIU/mL, n=8), whereas it remained stable in group 1 (22.36+/-4.98 microIU/mL, n=5 vs. 27.70+/-2.83 microIU/mL, n=5). Acute insulin release to glucose, acute C-peptide release to glucose (ACpRg), and mixed meal stimulation index were significantly decreased and time-to-peak C-peptide, 90-min glucose, and area under the curve for glucose were significantly increased when measured at time points preceding intervals where IGD occurred compared with intervals where there was no IGD.. The intravenous glucose tolerance test and mixed meal tolerance test may be useful in the prediction of IGD and should be essential components of the metabolic testing of islet transplant recipients.

Topics: Arginine; Awareness; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation; Postoperative Complications; Transplantation, Homologous

This retrospective study was designed to identify metabolic and immune predictors of early islet allograft failure.. We measured several metabolic and immunological markers at the time of pretransplant and several time points posttransplantation in 17 patients with long-term functioning graft (long fx) and 20 patients with short-term functioning graft (short fx).. The short fx group showed higher insulin resistance, altered proinsulin processing, lower soluble interleukin-2 receptor (sIL-2r) (marker of T-cell activation), and higher soluble FasL (marker of apoptosis) during the entire follow-up, particularly at time of failure.. Patients who experienced an early failure of islet allograft showed specific metabolic and immunological signs long before islet failure.

Topics: Adult; Annexin A5; C-Peptide; Fas Ligand Protein; Graft Rejection; Graft Survival; Humans; Insulin; Insulin Resistance; Islets of Langerhans Transplantation; Postoperative Complications; Retrospective Studies; Time Factors

Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth.. We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts.. Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients.. A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Eating; Female; Food; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Incretins; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Obesity, Morbid; Postoperative Complications

There are no effective indicators of graft dysfunction in islet transplantation. This study evaluated the role of the Continuous Glucose Monitoring System (CGMS) as an early indicator of graft dysfunction in islet transplant recipients.. In 5 islet allograft recipients, we retrospectively determined the date of graft dysfunction: 3 fasting blood glucose levels >7.8 mmol/L (140 mg/dL) and/or 3 postprandial blood glucose levels >10 mmol/L (180 mg/dL) in 1 week. We then determined 2 time points in respect to graft dysfunction, 5 to 9 months before (time point A) and 2 to 3 months before (time point B). For these 2 time points, we assessed the following: HbA1c, C-peptide (CP), C-peptide glucose ratio (CPGR), 90-minute glucose from mixed meal tolerance test, and percentage of capillary blood glucose levels >7.8 mmol/L (%CBG >7.8) in a 15-day interval (1 week before and after CGMS placement). From the CGMS recordings, we calculated the glucose variability and the percentage of time spent in hyperglycemia >7.8 mmol/L (%HGT >7.8) and >10 mmol/L (%HGT >10).. No difference was found between time points A and B for the following parameters: HbA1c, CP, CPGR, 90-minute glucose, %CBG >7.8, and %HGT >10. We observed a statistically significant increase from time point A to time point B in glucose variability (1.1 +/- 0.5 mmol/L to 1.6 +/- 0.6 mmol/L; P = .004), and in the %HGT >7.8 (11 +/- 12% to 22 +/- 18%; P = .036).. Glucose variability and %HGT >7.8 determined using CGMS are useful as early indicators of graft dysfunction in islet transplant recipients. Further studies with larger sample sizes will help validate these observations.

Topics: Adult; Blood Glucose; C-Peptide; Female; Humans; Immunosuppressive Agents; Islets of Langerhans Transplantation; Male; Middle Aged; Monitoring, Ambulatory; Monitoring, Physiologic; Postoperative Complications; Retrospective Studies; Transplantation, Homologous

To retrospectively evaluate the role of ultrasonography (US) with regard to the technique, complications, and therapeutic efficacy of percutaneous intrahepatic transplantation of human pancreatic islet cells with combined US and fluoroscopic guidance.. The institutional review board approved the study, and informed consent was obtained from all patients. After kidney transplantation, 34 uremic diabetic patients (20 men, 14 women; mean age, 40.9 years; age range, 29-61 years) underwent percutaneous intrahepatic transplantation of islet cells. Portal vein patency and liver echotexture were preliminarily assessed with color Doppler US. US also was used to identify early complications and presence (group A patients) or absence (group B patients) of hepatic parenchymal changes. Differences between the two groups in C peptide serum level and range were analyzed (Mann-Whitney test). Therapeutic efficacy of transplantation was assessed with regard to insulin independence period (rate and duration), exogenous insulin requirement, glycated hemoglobin, and C peptide level. A C peptide level of more than 0.5 ng/mL was considered to indicate well-functioning islet cells.. Fifty-eight procedures were technically successful, with a single puncture used in 51 of 58 patients. Complications occurred in three of 58 patients (hemoperitoneum, hemothorax, and thrombosis in one patient each) and were conservatively treated and resolved. Duration of insulin independence in 12 patients was more than 3 months (mean, 21 months). Well-functioning islet cells at 6 years were found in 19 of 34 patients. Hyperechoic parenchymal changes were evident at US in 12 of 34. No statistically significant difference in C peptide level was found between groups (P > .05), but a wider range of values was recorded in group B.. Complication rate of transplantation with US and fluoroscopic guidance was low. Well-functioning islet cells were found in about 50% of patients at 6 years of follow-up. Hepatic implantation of islet cells was evident on US images in more than one-third of patients.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Female; Fluoroscopy; Hemoglobins, Abnormal; Humans; Immunosuppression Therapy; Insulin; Islets of Langerhans Transplantation; Liver; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Treatment Outcome; Ultrasonography, Doppler, Color

Coronary artery disease (CAD) is the most common cause of death in patients with type 1 diabetes. Asymptomatic CAD is common in uremic diabetic patients, but its prevalence in nonuremic type 1 diabetic patients is unknown. The prevalence of CAD was determined by coronary angiography and the performance of noninvasive cardiac investigation evaluated in type 1 diabetic islet transplant (ITX) candidates with preserved renal function.. A total of 60 consecutive type 1 diabetic ITX candidates (average age 46 years [mean 24-64], 23 men, and 47% ever smokers) underwent coronary angiography, electrocardiographic stress testing (EST), and myocardial perfusion imaging (MPI) in a prospective cohort study. CAD was indicated on angiography by the presence of stenoses >50%. Models to predict CAD were examined by logistic regression.. Most subjects (53 of 60) had no history or symptoms of CAD; 23 (43%) of these asymptomatic subjects had stenoses >50%. CAD was associated with age, duration of diabetes, hypertension, and smoking. Although specific, EST and MPI were not sensitive as predictors of CAD on angiography (specificity 0.97 and 0.93, sensitivity 0.17 and 0.04, respectively) but helped identify two of three subjects requiring revascularization. EST and MPI did not enhance logistic regression models. A clinical algorithm to identify low-risk subjects who may not require angiography was highly sensitive but was applicable only to a minority (n = 8, sensitivity 1.0, specificity 0.27, negative predictive value 1.0).. Nonuremic type 1 diabetic patients with hypoglycemic unawareness and/or metabolic lability referred for ITX are at high risk for asymptomatic CAD despite negative noninvasive investigations. Aggressive management of cardiovascular risk factors and further investigation into optimal cardiac risk stratification in type 1 diabetes are warranted.

Topics: Adult; Aged; Awareness; Blood Pressure; C-Peptide; Coronary Angiography; Coronary Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Humans; Hypoglycemia; Islets of Langerhans Transplantation; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Smoking

Diabetic patients with end-stage renal disease have a high mortality rate. A combined kidney-pancreas transplant is associated with greater life expectancy. Pancreas islet transplantation is an alternative involving a lower degree of morbidity. We present two patients, of 41 and 37 years of age, with a long history of diabetes mellitus (C-peptide negative), both with a previous kidney transplant, who had been treated with 22 and 28 U of insulin/d, respectively. Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one patient required occasional doses of insulin, and the other patient more than 50% reduced dose. After the first implant neither patient had any episodes of unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no transplant-related complications.

Topics: Adult; Awareness; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Complications; Postoperative Period

For selected patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous kidney-pancreas (SKP) or pancreas after kidney (PAK) transplantation is the treatment of choice. However, it is frequently difficult to start a program for fear of serious intraabdominal complications in an immunosuppressed patient. We review our initial experience with these transplantations.. Twenty-three patients (20 SKP, 3 PAK) with type 1 diabetes mellitus received transplants between June 2000 and October 2003. All received immunosuppression therapy with thymoglobulin, prednisone, tacrolimus, and mycophenolate mofetil. The operation included portal venous drainage and exocrine enteric drainage. Rejections were biopsy-proved. Cytomegalovirus prophylaxis with gancyclovir was administered.. The mean follow-up is 13 months (range, 1-30 months) for recipients of mean age 39 +/- 7 years (17 men, 6 women). Mean cold ischemia time for kidney was 10.2 +/- 3.9 hours, and for pancreas was 10.5 +/- 3 hours. The rate of initial graft function was 100%. Graft rejection rate was 8%. The repeat laparotomy rate was 53% (12 patients), with a mean of 0.8 procedures per patient (range, 0 to 5). At the end of follow-up, patient survival was 95%, kidney survival was 85%, and pancreas survival was 83%. Patients with a functioning graft were insulin-free, with a mean fasting glucose concentration of 79 +/- 7 mg/dL, hemoglobin A1C of 4.5% (range, 4% to 4.9%) C-peptide of 5.9 ng/mL (range, 2.1 to 12 ng/mL), and a mean serum creatinine level of 1.6 mg/dL (range, 0.9 to 4.6 mg/dL). There was 1 death, due to posttransplantation lymphoproliferative disease confined to the pancreatic graft and abdominal sepsis at 3 months posttransplantation.. Our results are similar to those of other series of SPK or PAK transplantations: low acute rejection rates, frequent requirement for repeat laparotomy, and good patient and graft survival, permitting an excellent quality of life.

Topics: Adult; C-Peptide; Cytomegalovirus Infections; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Hematoma; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Reoperation; Time Factors

Islet transplantation can restore endogenous beta-cell function to subjects with type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as of 1 November 2004. Their mean age was 42.9 +/- 1.2 years, their mean duration of diabetes was 27.1 +/- 1.3 years, and 57% were women. The main indication was problematic hypoglycemia. Forty-four patients completed the islet transplant as defined by insulin independence, and three further patients received >16,000 islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those who became insulin independent received a total of 799,912 +/- 30,220 IE (11,910 +/- 469 IE/kg). Five subjects became insulin independent after one transplant. Fifty-two patients had two transplants, and 11 subjects had three transplants. In the completed patients, 5-year follow-up reveals that the majority ( approximately 80%) have C-peptide present post-islet transplant, but only a minority ( approximately 10%) maintain insulin independence. The median duration of insulin independence was 15 months (interquartile range 6.2-25.5). The HbA(1c) (A1C) level was well controlled in those off insulin (6.4% [6.1-6.7]) and in those back on insulin but C-peptide positive (6.7% [5.9-7.5]) and higher in those who lost all graft function (9.0% [6.7-9.3]) (P < 0.05). Those who resumed insulin therapy did not appear more insulin resistant compared with those off insulin and required half their pretransplant daily dose of insulin but had a lower increment of C-peptide to a standard meal challenge (0.44 +/- 0.06 vs. 0.76 +/- 0.06 nmol/l, P < 0.001). The Hypoglycemic score and lability index both improved significantly posttransplant. In the 128 procedures performed, bleeding occurred in 15 and branch portal vein thrombosis in 5 subjects. Complications of immunosuppressive therapy included mouth ulcers, diarrhea, anemia, and ovarian cysts. Of the 47 completed patients, 4 required retinal laser photocoagulation or vitrectomy and 5 patients with microalbuminuria developed macroproteinuria. The need for multiple antihypertensive medications increased from 6% pretransplant to 42% posttransplant, while the use of statin therapy increased from 23 to 83% posttransplant. There was no change in the neurothesiometer scores pre- versus posttransplant. In conclusion, islet transplantation can relieve glucose instability and problems with hypoglycemia. C-peptide secretion was maintained in the majority of subjects for up to 5 years, al

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypoglycemia; Insulin; Islets of Langerhans Transplantation; Male; Postoperative Complications; Survival Analysis; Time Factors; Treatment Outcome

Even recipients with satisfactory function of transplanted pancreas and kidney may show physical and/or social disability due to diabetic complications. Our aims were to evaluate diabetic complications influencing recipient quality of life and to assess patients' psychosociological status. Nineteen patients with functioning grafts who consented to take part in the study, underwent clinical evaluation and answered questions regarding their quality of life. Results showed excellent endocrine pancreatic function in 17 patients. In most recipients, insulin activity and C-peptide levels were elevated owing to systemic venous drainage. Opthalmological examination revealed blindness in 7 patients (in 4 cases with onset following SPKTx) and retinopathy in 13 patients (in 5 cases it appeared after SPKTx). Assessment of the cardiovascular system revealed satisfactory cardiac function in 16 of 19 patients; 4 patients underwent amputation of a lower limb following SPKTx. All 19 recipients admitted to a great benefit of transplantation; most patients declared ability to organize their life activity and social functions and 4 had regular employment. Conversely, most patients were afraid of graft loss, and half were often sad and even depressed.

Topics: Blindness; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Employment; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Pancreas Transplantation; Postoperative Complications; Quality of Life

The success of sirolimus and low-dose tacrolimus in islet cell transplantation has influenced many transplant centers to utilize this novel regimen. The long-term safety and tolerability of this steroid-free immunosuppressive protocol for allogeneic islet transplantation has yet to be determined.. We transplanted 26 adult patients with long standing type 1 diabetes mellitus between April 2000 and June 2004. Immunosuppression consisted of induction with daclizumab and maintenance therapy with tacrolimus and sirolimus. Adverse events (AEs) in patients were followed and graded using the Common Terminology Criteria for Adverse Events, version 3.0 (National Cancer Institute).. To date, the majority of patients were able to remain on the immunosuppression combination for up to 22+/-11 months. Four patients were successfully converted to Mycophenolate Mofetil due to tacrolimus-related toxicity. Withdrawal from immunosuppression was decided in four patients due to hypereosinophilic syndrome, parvovirus infection, aspiration pneumonia, and severe depression, respectively. Six patients required filgrastim therapy for neutropenia. Transient elevation of liver enzymes was observed in most patients early after islet infusion. Increased LDL in 20 patients required medical treatment.. There was a varying range of AEs, most of them mild and self-limiting; however, some required urgent medical attention. The majority of patients were able to tolerate and remain on this effective regimen. To date, no deaths, cytomegalovirus disease, graft-versus-host disease, or posttransplant lymphoproliferative disease has been observed.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Transplantation, Homologous

The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence and clinical characteristics of PTDM in Korean renal allograft recipients undergoing tacrolimus-based immunosuppression were examined.. A total of 21 patients taking tacrolimus as primary immunosuppressant were recruited and tested with a serial 75-g oral glucose tolerance test at 0, 1, 3, and 6 months after renal transplantation.. The cumulative incidence of PTDM was 52.4% at 1 month and 57.1% at 3 and 6 months. The baseline characteristics of the PTDM group were old age (especially >40 years), a high BMI, a high fasting glucose level, a high plasma insulin level, and increased insulin resistance. Among these parameters, old age was the only independent risk factor. The insulin secretory capacity in the PTDM group was maximally suppressed 3 months after transplantation. Thereafter, it was gradually restored along with dose reduction of tacrolimus.. Routine screening for PTDM is necessary in patients over 40 years of age who are undergoing a relatively higher dose tacrolimus therapy during the early course of postrenal transplantation.

Topics: Adult; C-Peptide; Cholesterol; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Incidence; Insulin; Kidney Transplantation; Male; Postoperative Complications; Societies, Medical; Tacrolimus; Time Factors; Triglycerides; United States

The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state.. This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration.. During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels.. The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Graft Survival; Humans; Hypoglycemic Agents; Insulin; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Sulfonylurea Compounds; Survival Analysis; Time Factors

An end-stage renal disease patient on long-term peritoneal dialysis was admitted with dizziness, fatigue, hypoglycemia, and hypotension. The hypotension resolved with intravenous normal saline, but the hypoglycemia persisted for 3 days despite an intravenous dextrose drip and discontinuation of gabapentin. The patient became normoglycemic on the fourth day of admission. None of the known causes for the hypoglycemia were identified except gabapentin, the dose of which was recently doubled 1 month before admission. Insulin and C-peptide levels were high during the hypoglycemic episode and returned to normal after discontinuation of gabapentin. The patient remains off gabapentin and has had no further episodes of hypoglycemia. To our knowledge, this is the first case of hypoglycemia induced by gabapentin.

Topics: Acetates; Amines; C-Peptide; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Gluconeogenesis; Humans; Hypoglycemia; Hypotension; Insulin; Kidney Cortex; Kidney Failure, Chronic; Liver; Middle Aged; Pancreas; Parathyroidectomy; Peritoneal Dialysis; Postoperative Complications

Topics: C-Peptide; Cytomegalovirus; Cytomegalovirus Infections; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Incidence; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Postoperative Complications; Transplantation, Homologous; Virus Replication

As a result of advances in both immunosuppressive protocols and pancreatic islet isolation techniques, insulin independence has recently been achieved in several patients with type 1 diabetes mellitus via pancreatic islet transplantation (PIT). Although the dissemination of immunosuppressive protocols is quite easy, transferring the knowledge and expertise required to isolate a large number of quality human islets for transplantation is a far greater challenge. Therefore, in an attempt to centralize the critical islet processing needed for islet transplantation and to avoid the development of another islet processing center, we have established a collaborative islet transplant program between two geographically distant transplant centers.. Three consecutive patients with type 1 diabetes mellitus with a history of severe hypoglycemia and metabolic instability underwent PIT at the Methodist Hospital (TMH), Houston, Texas, using pancreatic islets. All pancreatic islets were isolated from pancreata procured in Houston and subsequently transported for isolation to the Human Islet Cell Processing Facility of the Diabetes Research Institute (DRI) at the University of Miami, Miami, Florida. Pancreatic islets were isolated at DRI after enzymatic ductal perfusion (Liberase-HI) by the automated method (Ricordi Chamber) using endotoxin-free and xenoprotein-free media. After purification, the islets were immediately transported back to TMH and transplanted via percutaneous transhepatic portal embolization. Immunosuppression consisted of sirolimus, tacrolimus, and daclizumab.. After donor cross-clamp in Houston, donor pancreata arrived at DRI and the isolation process began within 6.5 hr in all cases (median, 5.4 hr; range, 4.8-6.5 hr). At the completion of the isolation process, the islets were immediately transported back to TMH and transplanted. All three patients attained sustained insulin independence after transplantation of 395,567, 394,381, and 563,206 pancreatic islet equivalents (IEQ), respectively. Despite insulin independence, the first two patients received less than 10,000 IEQ/kg; therefore, to increase their functional pancreatic islet reserve, they underwent a second islet transplant with 326,720 and 768,132 IEQ, respectively. Posttransplantation follow-up for these three patients is 4, 3, and 0.5 months, respectively. The mean glycosylated hemoglobin values have been dramatically reduced in the first two patients. In addition, the mean amplitude of glycemic excursions have also been reduced in all three recipients (patient 1: before transplantation 197 mg/dL vs. after transplantation 61 mg/dL; patient 2: before transplantation 202 mg/dL vs. after transplantation 52 mg/dL; patient 3: before transplantation 245 mg/dL vs. after transplantation 58 mg/dL) after PIT. All pancreatic islet allografts demonstrated the ability to respond to an in vitro glucose stimulus at the DRI before shipment and at TMH after shipment and final processing with a median stimulation index of 2.1 and 2.2, respectively. None of the transplant recipients have had a hyper- or hypoglycemic episode since PIT and no complications have occurred.. These early data demonstrate that (1) pancreatic islets remain viable after shipment to remote transplant sites; (2) pancreatic islet isolation techniques and experience can be concentrated at a small number of regional facilities that could supply islets to remote transplant centers; and (3) insulin independence via PIT can be achieved using a remote pancreatic islet isolation center.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cooperative Behavior; Diabetes Mellitus, Type 1; Eating; Follow-Up Studies; Graft Survival; Humans; In Vitro Techniques; Insulin; Interinstitutional Relations; Islets of Langerhans; Islets of Langerhans Transplantation; Middle Aged; Postoperative Complications; Tissue and Organ Procurement; Transplantation, Homologous

Clinical islet transplantation is gaining acceptance as a potential therapy, particularly for subjects who have labile diabetes or problems with hypoglycemic awareness. The risks of the procedure and long-term outcomes are still not fully known. We have performed 54 islet transplantation procedures on 30 subjects and have detailed follow-up in 17 consecutive Edmonton protocol-treated subjects who attained insulin independence after transplantation of adequate numbers of islets. Subjects were assessed pretransplant and followed prospectively posttransplant for immediate and long-term complications related to the procedure or immunosuppressive therapy. The 17 patients all became insulin independent after a minimum of 9,000 islets/kg were transplanted. Of 15 consecutive patients with at least 1 year of follow-up after the initial transplant, 12 (80%) were insulin independent at 1 year. In 14 subjects who have maintained demonstrable C-peptide secretion, glucose control has been stable and glycemic lability and problems with hypoglycemic reactions have been corrected. After 2 of the 54 procedures, some thrombosis was detected in the portal vein circulation. Five subjects had bleeding related to the percutaneous portal vein access procedures: three required transfusion alone, and in one subject, who had a partial thrombosis of the portal vein, an expanding intrahepatic and subscapular hemorrhage occurred while on anticoagulation, requiring transfusion and surgery. Elevated liver function test results were found in 46% of subjects but resolved in all. Complications related to the therapy have been hypercholesterolemia requiring statin therapy in 65%; a rise in creatinine in two patients, both of whom had preexisting renal disease; a rise in protein in four, all of whom had preexisting proteinuria; and antihypertensive therapy increased or started in 53%. Three of the 17 patients have required retinal laser photocoagulation. There have been no cases of posttransplant lymphoproliferative disorder or cytomegalovirus infection, and no deaths. The acute insulin response to arginine correlated better with transplanted islet mass than acute insulin response to glucose (AIR(g)) and area under the curve for insulin (AUC(i)), but the AIR(g) and AUC(i) were more closely related to glycemic control. The AUC(i) directly posttransplant was lower in those who eventually became C-peptide deficient. Our results, with a maximum follow-up of 34 months, indicate that prolonged ins

Topics: Adult; Age of Onset; Blood Glucose; C-Peptide; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans Transplantation; Male; Portal Vein; Postoperative Complications; Time Factors; Treatment Outcome

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were

Topics: Adult; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Insulin; Insulin Secretion; Islets of Langerhans Transplantation; Male; Postoperative Complications; Postoperative Period; Treatment Outcome

Topics: C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Taiwan; Time Factors

To investigate the late sequellae of necrotizing pancreatitis on the endocrine function of the pancreas.. Twenty patients, 15 men (mean +/- SEM age 52.2+/-2.6 years and BMI 26.8+/-0.8 kg/m2) and 5 women (age 51.0+/-7.6 years and BMI 26.7+/-0.8 kg/m2) were submitted to a glucagon stimulation test 63 (range 8-136) months after an attack of pancreatitis. All nondiabetic patients (n = 15) were also submitted to an oral glucose tolerance test. For comparison, 16 healthy volunteers, 8 men (age 56.0+/-0.9 years and BMI 26.3+/-0.4 kg/m2) and 8 women (age 50.5+/-1.0 years and BMI 28.2+/-0.6 kg/m2), were also studied.. Five patients (25%) had diabetes mellitus and needed insulin treatment, 6 patients (30%) had an impaired glucose tolerance (IGT). Nondiabetic patients (IGT included) had a significantly higher basal insulin level (15.8+/-1.9 vs. 10.9 +/-2.2 mU/l, p < 0.05) and a lower glucose/insulin ratio (p < 0.05) compared with controls. The serum concentrations of insulin and C peptide, after stimulation with glucagon, calculated as peak value, maximal increment and as area under the curve were not significantly different in the nondiabetic patients compared to controls. The subgroup of IGT patients had a significantly higher basal C peptide (p < 0.05) and a reduced maximal increment (p < 0.05).. After nonresectional therapy for necrotizing pancreatitis, there is a high prevalence of disturbances in glucose metabolism. Patients with IGT have signs of both loss of beta-cell function and insulin resistance.

Topics: C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Postoperative Complications

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65% for ED, 60% for BD, and 47% for DO. This surgical method has become the preferred technique in our unit.

Topics: Adult; C-Peptide; Female; Glucose Tolerance Test; Graft Rejection; Graft Survival; Humans; Male; Middle Aged; Pancreas Transplantation; Postoperative Complications; Treatment Outcome

Hypoglycaemia is an important complication of insulin treatment in Type 1 diabetes mellitus (DM). Pancreas transplantation couples glucose sensing and insulin secretion, attaining a distinctive advantage over insulin treatment. We tested whether successful transplantation can avoid hypoglycaemia in Type 1 DM. Combined kidney and pancreas transplanted Type 1 DM who complied with good function criteria (KP-Tx, n = 55), and isolated kidney or liver transplanted non-diabetic subjects on the same immunosuppressive regimen (CON-Tx, n = 14), underwent 1-day metabolic profiles in the first 3 years after transplantation, sampling plasma glucose (PG) and pancreatic hormones every 2 hours. KP-Tx had lower PG than CON-Tx in the night and in the morning and higher insulin concentrations throughout the day. KP-Tx had lower PG nadirs than CON-Tx (4.40+/-0.05 vs 4.96+/-0.16 mmol l(-1), ANOVA p = 0.001). Nine per cent of KP-Tx had hypoglycaemic values (PG < or = 3.0 mmol l(-1)) in the profiles, both postprandial and postabsorptive, whereas none of CON-Tx did (p < 0.02). In conclusion, after pancreas transplantation, mild hypoglycaemia is frequent, although its clinical impact is limited. Compared to insulin treatment in Type 1 DM, pancreas transplantation improves but cannot eliminate hypoglycaemia.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Humans; Hypoglycemia; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Time Factors

Topics: C-Peptide; Diabetes Mellitus, Type 1; Germany; Glycated Hemoglobin; Graft Survival; Humans; Insulin; International Cooperation; Islets of Langerhans Transplantation; Male; Postoperative Complications; Sweden; Time Factors; Tissue and Organ Procurement

Glucagon-like peptide 1 (GLP-1[7-36 amide]) is an incretin hormone primarily synthesized in the lower gut (ileum, colon/rectum). Nevertheless, there is an early increment in plasma GLP-1 immediately after ingesting glucose or mixed meals, before nutrients have entered GLP-1 rich intestinal regions. The responsible signalling pathway between the upper and lower gut is not clear. It was the aim of this study to see, whether small intestinal resection or colonectomy changes GLP-1[7-36 amide] release after oral glucose. In eight healthy controls, in seven patients with inactive Crohn's disease (no surgery), in nine patients each after primarily jejunal or ileal small intestinal resections, and in six colonectomized patients not different in age (p = 0.10), body-mass-index (p = 0.24), waist-hip-ratio (p = 0.43), and HbA1c (p = 0.22), oral glucose tolerance tests (75 g) were performed in the fasting state. GLP-1[7-36 amide], insulin C-peptide, GIP and glucagon (specific (RIAs) were measured over 240 min.. Repeated measures ANOVA, t-test (significance: p < 0.05). A clear and early (peak: 15-30 min) GLP-1[7-36 amide] response was observed in all subjects, without any significant difference between gut-resected and control groups (p = 0.95). There were no significant differences in oral glucose tolerance (p = 0.21) or in the suppression of pancreatic glucagon (p = 0.36). Colonectomized patients had a higher insulin (p = 0.011) and C-peptide (p = 0.0023) response in comparison to all other groups. GIP responses also were higher in the colonectomized patients (p = 0.0005). Inactive Crohn's disease and resections of the small intestine as well as proctocolectomy did not change overall GLP-1[7-36 amide] responses and especially not the early increment after oral glucose. This may indicate release of GLP-1[7-36 amide] after oral glucose from the small number of GLP-1[7-36 amide] producing L-cells in the upper gut rather than from the main source in the ileum, colon and rectum. Colonectomized patients are characterized by insulin hypersecretion, which in combination with their normal oral glucose tolerance possibly indicates a reduced insulin sensitivity in this patient group. GIP may play a role in mediating insulin hypersecretion in these patients.

Topics: Adult; Aged; C-Peptide; Colectomy; Crohn Disease; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Tolerance Test; Humans; Insulin; Intestine, Large; Intestine, Small; Male; Middle Aged; Peptide Fragments; Postoperative Complications

Chronic pancreatitis (CP) leads to deterioration of the endocrine pancreatic function by fibrotic destruction. The aim of the present study was to investigate whether resection or duct drainage in patients with CP would have a direct impact on the pancreatic beta cell function. An intravenous glucose tolerance test (IVGTT) was performed before, after and in some cases 3 months after operation in ten patients each of whom had been treated by either resection or duct drainage. Three patients undergoing pancreatic resection for cancer served as controls. Beta cell function was assessed by glucose elimination (K-values), insulin and C-peptide response. K-Values in patients with CP were not significantly influenced after resection (1.93 +/- 0.78/2.13 +/- 0.72; n.s.) or drainage (1.26 +/- 0.47/1.54 +/- 0.58; n.s.) but reduced in all three tumor patients (2.23 +/- 0.55/1.23 +/- 0.43). The initial insulin response [microU/ml] in CP patients was also not altered after resection (19.7 +/- 17.3/16.0 +/- 18.2; n.s.) or after drainage (16.7 +/- 16.5/13.0 +/- 9.0; n.s.), whereas all three resected tumor patients showed reduced values (42.9 +/- 15.7/17.5 +/- 3.8). Stimulated C-peptide synthesis [ngmin/ml] was not substantially lowered in patients resected for CP (90.5 +/- 85.6/73.8 +/- 48.9; n.s.) or in the drainage group (121.3 +/- 67.5/98.0 +/- 57.2; n.s.), but this parameter was decreased in every tumor patient postoperatively (157.8 +/- 66.9/125.1 +/- 69.6). Resection in patients with chronic pancreatitis did not inevitably result in loss of beta cell function. Parenchyma-preserving drainage procedures had no measurable advantage in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Chronic Disease; Drainage; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatitis; Postoperative Complications

The secretion of hormones stimulating and inhibiting gastric secretory activity was studied in 85 patients with postvagotomy syndromes. The somatropin level was found to increase significantly in gastrostasis. The lower values of the blood insulin and C-peptide content in patients with recurrent ulcers was evidently associated either with insufficiency of the pancreatic insular apparatus or with partial vagal denervation, increased STH level, and plausible inhibiting effect of glucagon. Increased somatostatin secretion in the dumping syndrome, gastrostasis, and peptic ulcers may be due to the encountered hypergastrinemia.

Topics: C-Peptide; Constriction, Pathologic; Diarrhea; Dumping Syndrome; Gastric Acid; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Neurotransmitter Agents; Peptic Ulcer; Postoperative Complications; Recurrence; Somatostatin; Stomach Diseases; Syndrome; Vagotomy, Proximal Gastric

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Duodenitis; Duodenum; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Pancreas Transplantation; Postoperative Complications; Reference Values; Reoperation; Transplantation, Homologous; Urinary Bladder

Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604 +/- 19562 IU/24 h). Fistula output was 280 +/- 87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300-750 micrograms/day. In all patients a progressive reduction in fistula output was observed after a mean of 16 + 2 days. Fistula flow rate dropped to 24 +/- 10 ml/24 h--a reduction of 95% +/- 5% and drainage was subsequently stopped. Sonographic follow-up did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12-44 months after surgery.

Topics: Adult; C-Peptide; Humans; Kidney Transplantation; Octreotide; Pancreas Transplantation; Pancreatic Fistula; Postoperative Complications

The insulinoma is the most common pancreas tumour with endocrine activity, with more than 2,000 cases being described in the literature worldwide. The first successful extirpation was performed by Graham in 1928. Clinical appearance is characterized by severe paroxysmal hypoglycaemia together with inadequately increased serum insulin levels. Surgery is indicated in such situations because of limited effectiveness of medicamentous therapy. Surgical approach and long-time results are discussed in this paper, with reference being made to 13 cases of the authors.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Follow-Up Studies; Gastrins; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulinoma; Male; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Reoperation

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Graft Survival; Humans; Immunosuppression Therapy; Kidney Transplantation; Pancreas Transplantation; Pancreatic Ducts; Postoperative Complications

To determine the cause of hyperglycemia appearing after pancreas transplantation in type I diabetic recipients, we performed 65 oral glucose tolerance tests with serum insulin and C-peptide determinations in 32 patients with pancreas grafts functioning two or more months following transplantation. We correlated these results with estimates of graft size obtained by magnetic resonance imaging (MRI) and values of urinary amylase as a measure of pancreatic exocrine function. A total of 33 studies were obtained in 20 patients at times of normal glucose tolerance, and normal ranges for serum insulin and C-peptide levels were established; 32 studies in 17 patients during periods of glucose intolerance revealed values of serum insulin and C-peptide that were within the normal range, though the time to peak values was delayed to 2 hr, characteristic of type II diabetes. Only 3 of 17 patients examined by MRI had significant pancreatic allograft atrophy. These patients also had low urinary amylase excretion, and the only values for serum C-peptide that were below the normal range. The other 14 hyperglycemic patients had normalized pancreas grafts, normal urinary amylase excretion, and normal values for serum insulin and C-peptide. In our experience, then, in 76% of patients with hyperglycemia more than 2 months following pancreas transplantation, the cause was appearance of type II diabetes rather than destruction of the allograft with recurrence of type I diabetes. This observation has important implications for the definition of pancreas allograft failure and for the management of pancreas allograft recipients with hyperglycemia.

Topics: Amylases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Insulin; Magnetic Resonance Imaging; Pancreas Transplantation; Postoperative Complications; Recurrence; Reference Values

Topics: Amylases; Atrophy; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Pancreas; Pancreas Transplantation; Postoperative Complications

An intravenous glucose tolerance test was carried out to compare chronic pancreatitis patients (n = 17) who had undergone partial duodenopancreatectomy with (n = 9) and without (n = 8) occlusion of the residual pancreatic duct by Prolamin. The results obtained in 10 healthy volunteers were plotted as background information reflecting the normal metabolic response. Insulin- and C-peptide secretion were greatly decreased after both resection alone, and resection plus occlusion. However, the glucose tolerance (integrated glucose; K-values) appeared relatively well preserved in the two groups. The decrease in insulin appeared more marked after resection plus occlusion as compared with the non-occluded group. It is concluded that partial duodenopancreatectomy without or with ductal occlusion impairs insulin secretion, and leaves tolerance to an intravenous glucose load relatively stable. The mechanism underlying the latter observation is unknown at present.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Methods; Middle Aged; Pancreatitis; Postoperative Complications

The diagnosis of an insulin producing tumour can be confirmed by a minimum of biochemical investigations. Its preoperative localisation is more difficult. Sonogram, Computertomogram, selective angiography and percutaneous transhepatic collecting of blood samples for insulin analysis from the portal system were preoperative measured to localize the tumours in 32 of 37 patients of our series. In 2 patients intraoperative tumour localisation by measurement of incorporated p32 proved to be effective. In B-cell-carinomas pancreas resection is the adequate therapy. With regard to the therapeutic effects a high risk is involved in the 'blind' left or right sited resection of non-localized tumours.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Blood Glucose; C-Peptide; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hyperinsulinism; Infant; Insulin; Insulinoma; Male; Middle Aged; Pancreatic Neoplasms; Postoperative Complications

A patient recovering normally from a biopsy and subtotal removal of a malignant brain tumor became severely hypoglycemic on the ward and died. The differential diagnosis eliminated disease as a possible cause, and medication error on the floor was also ruled out. Deliberate administration of a massive dose of insulin intravenously seemed to be the only alternative. A careful investigation supported the likelihood of a criminal act. The patient's wife came under suspicion and was subsequently arrested, charged with murder, and convicted. This sequence of events created three problems that fell outside of our normal professional training and experience as physicians. First, we were slow to suspect foul play in our search for an unusual cause. Second, the steps taken to protect the patient against further risk without denying reasonable rights to family or arousing the suspect's suspicions needed strengthening. Third, even though the occurrence of these events in a hospital allowed an unusual degree of evidence documenting the allegations to be accumulated, key parts of the evidence could not be used. The routine hospital handling of laboratory tests critical to support of the accusations was not sufficient to meet the demands of the legal system, which has its own criteria. We discuss the issues in managing these problems.

Topics: Blood Glucose; Brain Neoplasms; C-Peptide; Female; Forensic Medicine; Frontal Lobe; Homicide; Hospital Records; Humans; Insulin; Male; Middle Aged; Missouri; Postoperative Complications; Records

This study was designed to investigate the long-term effects of early pancreatic resection for acute necrotizing pancreatitis. During 1973-1978 40 resections were performed in our clinic. Eleven patients died initially (28 per cent). None of the four further deaths was due to pancreatitis or associated disorders. Twenty-four patients were re-examined 5-11 years after resection--one patient refused to participate. Five had not been able to return to work because of severe polyneuropathy; one more had retired because of chronic pancreatitis in the pancreatic remnant. Polyneuropathy was found in five further patients. The reason for this high incidence of polyneuropathy (42 per cent) remains unknown. Eight patients still drank excessive alcohol; three of them had had recurrent pancreatitis and dyspepsia, and insulin requiring diabetes. All but 2 (92 per cent) had diabetes, 14 needing insulin--half of them at 6 months to 6 years after the resection. Moreover, 11 patients (46 per cent) suffered from dyspeptic symptoms. The results suggest that because of the high frequency of late complications, in addition to the early complications, early resection of pancreas should be critically re-evaluated as the treatment for acute necrotizing pancreatitis. If resection is used in patients with extreme pancreatic necrosis, careful and continuous postoperative follow-up will be needed.

Topics: Acute Disease; Adult; Aged; C-Peptide; Follow-Up Studies; Humans; Middle Aged; Necrosis; Pancreas; Pancreatectomy; Pancreatitis; Postoperative Complications; Time Factors

The finding of hypoglycemia after the surgical removal of a pheochromocytoma in two patients in a previous study led to monitoring of the serum glucose and plasma C-peptide levels in two other patients with a pheochromocytoma and one with unilateral adrenocortical hyperplasia. In the two patients with a pheochromocytoma endogenous insulin secretion, as measured by a C-peptide assay, was suppressed before removal of the tumours and resumed immediately after removal. The serum glucose levels decreased in these patients, but sufficient intravenous administration of glucose prevented postoperative hypoglycemia. In the patient with adrenocortical hyperplasia the plasma C-peptide level was not decreased before tumour removal, nor did it increase abruptly following removal. It therefore seems likely that the rapid fall in the serum glucose level following removal of a pheochromocytoma is caused by prompt resumption of beta-cell activity, with rebound hyperinsulinism.

Topics: Adrenal Cortex Diseases; Adrenal Gland Neoplasms; Blood Glucose; C-Peptide; Female; Humans; Hyperinsulinism; Hyperplasia; Male; Middle Aged; Pheochromocytoma; Postoperative Complications

Late results were obtained from the follow up of 48 patients with chronic pancreatitis, who underwent partial duodenopancreatectomy. We measured the rest function of the remaining B-cells after resection by daily glucose profile, i.v.-gtt, measurements of the glucagon stimulated C-peptide-output and the amount of C-peptide in the 24-h-urine. In 9% of the cases the operation induced diabetes in addition to the already existing 31%. 3/4 of the nondiabetics showed a latent diabetic metabolism (K value < 1.0). The cause of this, as shown by the C-peptide-analysis, was the loss of the endocrine functional reserve following pancreas resection because of chronic pancreatitis. Therapeutically great differences resulted in reaching and equilibrium of serum glucose in the pancreas resected insulin-dependent patients, because they were dependent on carbohydrates for energy. The tendency to hypoglycaemia represented an additional endangerment.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Duodenum; Follow-Up Studies; Humans; Islets of Langerhans; Pancreatectomy; Pancreatitis; Postoperative Complications