trypsinogen and Diabetes-Mellitus--Type-1

Type 1 diabetes (T1D) is considered a pancreatic beta cell-specific disease that results in absolute insulin deficiency. Nevertheless, clinical studies from 1940 onwards showed that patients with T1D had an abnormal exocrine pancreas due to the presence of subclinical exocrine insufficiency and acinar atrophy. Exocrine abnormalities are an important, and mostly neglected, characteristic associated with T1D. It is however still unclear whether the exocrine dysfunction in T1D is a primary damage caused by the same pathogenic event that led to beta cell destruction or secondary to beta cell loss. In this review, we collect evidence supporting the hypothesis that T1D is a combined endocrine-exocrine disease in which the loss of functional beta cell mass is most clinically apparent.

Topics: Animals; Diabetes Mellitus, Type 1; Humans; Insulin-Secreting Cells; Pancreas, Exocrine; Pancreatic Elastase; Pancreatitis; Trypsinogen

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Pancreas Transplantation; Pancreatic Diseases; Pancreatitis; Protease Inhibitors; Radioimmunoassay; Trypsin; Trypsinogen

Exocrine pancreas abnormalities are increasingly recognized as features of type 1 diabetes. We previously reported reduced serum trypsinogen levels and in a separate study, smaller pancreata at and before disease onset. We hypothesized that three pancreas enzymes (amylase, lipase, and trypsinogen) might serve as serological biomarkers of pancreas volume and risk for type 1 diabetes. Amylase, lipase, and trypsinogen were measured from two independent cohorts, together comprising 800 serum samples from single-autoantibody-positive (1AAb

Topics: Animals; Diabetes Mellitus, Type 1; Humans; Linear Models; Lipase; Logistic Models; Magnetic Resonance Spectroscopy; Pancreas; Trypsinogen

Thrombosis of the pancreas graft is the main cause of early graft loss in pancreas transplantation. We investigated whether hypercoagulability develops locally in the pancreas and contributes to thrombosis formation because of ischemia or reperfusion injury. It was further hypothesized that this might be induced by excessive intravascular trypsin activity.. Ten Patients undergoing pancreas transplantation were studied. In addition to the standard operation a 14 French catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were drawn simultaneously from the splenic vein of the pancreas graft (local samples) and the radial artery (systemic samples) at 0,1,2,5,10,30, and 60 minutes after reperfusion.. After reperfusion a progressive hypercoagulability developed locally in the pancreas as seen by an increase of thrombin-antithrombin complexes and only a transient increase of plasmin-antiplasmin complexes. In addition antithrombin 3 and protein c decreased systemically. The alterations seem not to be triggered by trypsin because trypsin activity locally remained low despite trypsinogen release and activation as assessed by trypsinogen activation peptides.. Local hypercoagulability might contribute to the development of graft thrombosis, however, the mechanism seems not to be related to ectopic trypsin activation.

Topics: alpha-2-Antiplasmin; Antithrombins; Blood Coagulation; Diabetes Mellitus, Type 1; Female; Fibrinolysin; Humans; Kidney Failure, Chronic; Male; Oligopeptides; Pancreas; Pancreas Transplantation; Postoperative Complications; Protein C; Thrombin; Thrombosis; Time Factors; Trypsin; Trypsinogen

Topics: Amylases; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Follow-Up Studies; Glucose Tolerance Test; Graft Rejection; Humans; Kidney Transplantation; Kinetics; Pancreas Transplantation; Time Factors; Transplantation, Homologous; Trypsinogen

Topics: Actuarial Analysis; Amylases; Biomarkers; Creatinine; Diabetes Mellitus, Type 1; Follow-Up Studies; Graft Rejection; Humans; Kidney Transplantation; Pancreas Transplantation; Survival Analysis; Time Factors; Treatment Failure; Trypsinogen

To date one of the major dilemmas in clinical pancreas transplantation is the lack of a reliable indicator for pancreas rejection. In a consecutive series of 52 patients undergoing simultaneous pancreas and kidney (SPK) transplantation with bladder drainage technique between October 1991 and December 1992 a new test using serial levels of serum human anodal trypsinogen (HAT) was evaluated for its efficacy to detect pancreas rejection. Postoperative baseline levels of HAT were compared to peak HAT values at time of rejection. HAT profiles at time of rejection were calculated and compared to profiles of urinary amylase, serum amylase, fasting blood sugar and serum creatinine. In this series one year patient survival was 97%, graft survival of the pancreas 86% and of the kidney 90%. In 71% of the patients at least one rejection episode occurred. At time of kidney-biopsy proven rejection with a concurrent serum creatinine rise a significant HAT level rise to more than 1000 ng/ml was observed from baseline levels of 200 ng/ml (P < 0.001) indicating kidney and pancreas rejection (73%). Urinary amylase levels decreased in the majority of rejection episodes at the same time from baseline levels to less than 20,000 U/l. In 25% of the rejection episodes a significant serum creatinine rise was observed without a HAT rise or urinary amylase decrease indicating kidney-only rejection, while in 2% a urinary amylase decrease and simultaneous HAT also was observed with a negative kidney biopsy indicating pancreas-only rejection. We feel that increase in HAT levels significantly correlates with pancreas rejection. After SPK, determination of HAT is an additional helpful non-invasive test. In pancreas transplantation alone HAT can be a useful indicator to detect rejection and facilitate timing of a pancreas biopsy and initiation of antirejection treatment.

Topics: Adult; Amylases; Biomarkers; Blood Urea Nitrogen; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Graft Rejection; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Postoperative Period; Reproducibility of Results; Time Factors; Transplantation, Homologous; Trypsinogen

A preliminary investigation of the role of ultrasound, including color and duplex Doppler, was performed in recipients of cadaveric pancreatico-duodenal transplants. Twenty such examinations were done on three patients. Three different complications were noted: rejection, pancreatitis, and peripancreatic abscess. The mean normal resistive index (RI) was 0.71 +/- 0.12. The normal allograft anteroposterior (AP) dimension ranged from 1.5 to 2.0 cm. Intraparenchymal and main feeding vessels were demonstrated easily. RI calculations alone were not helpful in diagnosing graft rejection. However, this diagnosis can be made using a new biochemical marker, serum anodal trypsinogen. We conclude that when used in conjunction with a reliable biochemical marker for rejection (serum anodal trypsinogen), ultrasound, including color and duplex Doppler, provides an important adjunct for the rapid, inexpensive, and complete evaluation of patients with pancreatico-duodenal transplants.

Topics: Cadaver; Diabetes Mellitus, Type 1; Duodenum; Graft Rejection; Humans; Pancreas Transplantation; Pancreatitis; Postoperative Complications; Trypsinogen; Ultrasonics; Ultrasonography

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; Infant; Male; Reference Values; Time Factors; Trypsin; Trypsinogen