c-peptide and Pancreatitis

Chronic pancreatitis (ChP) is the most frequent cause of pancreatogenous diabetes mellitus (DM). This kind of DM is a typical case of acquired insulin secretion deficiency. The group under scrutiny consisted of 122 patients with ChP. The average age of the 88 men was 42.9 and that of the 34 women was 54.4 years. According to pancreatography and to the presence of calcifications the patients were divided into four group by gravity of the morphological pictures at ERCP. The control group of healthy persons was made up of 15 men and 10 women. The presence of glucose intolerance was rated by the oral glucose tolerance test (oGTT) after 75 g glucose. The volume of endogenous secretion of insulin was studied by measuring IRI and C-peptide fasting and after stimulation. To measure the damage of pancreatic exocrine secretion we used function test (Spofagnost-Pankenzan test). In our own group of 122 patients we found decreased glucose tolerance in 72 (59%). 41% were cases of DM, 18% suffered from impaired glucose tolerance (IGT). As the results of stimulated C-peptide tests suggest, practically all patients with ChP corroborated by morphological changes in the pancreatic duct system at ERCP have decreased endogenous insulin secretion compared with healthy persons, and that includes even those normal glucose tolerance rated by results of oGTT We were able to prove a statistically significant relationship between the degree of morphological changes in the pancreatic duct system and the values of C-peptide. The mean values of the Spofagnost test showed significant differences between patients with normal glucose tolerance and DM.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 +/- 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity.. Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50-72) with BMI 23.1 kg/m(2) (20.3-25.5) and HbA(1c) 8.0% (6.9-11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41-62) with BMI 21.9 kg/m(2) (17.6-27.3) and HbA(1c) 7.8% (6.2-12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean +/- SEM) showed insulin resistance amounting to 1.9 +/- 0.3 and 1.7 +/- 0.5 in the two groups, respectively.. In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9-10.1) and 7.2 mmol/l (3.1-10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient.. We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Kinetics; Middle Aged; Pancreatitis; Peptide Fragments; Protein Precursors

The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20-120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m(2)); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1alpha gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All participants underwent three hyperglycemic clamps (2 h, 15 mM) with continuous infusion of saline, 1 pmol GLP-1 (7-36)amide/kg body weight.min or 4 pmol GIP pmol/kg body weight.min. The early-phase (0-20 min) plasma insulin response tended to be enhanced by both GIP and GLP-1, compared with glucose alone, in all five groups. In contrast, the late-phase (20-120 min) plasma insulin response to GIP was attenuated, compared with the plasma insulin response to GLP-1, in all five groups. Significantly higher glucose infusion rates were required during the late phase of the GLP-1 stimulation, compared with the GIP stimulation. In conclusion, lack of GIP amplification of the late-phase plasma insulin response to glucose seems to be a consequence of diabetes mellitus, characterizing most, if not all, forms of diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Male; Middle Aged; Neurotransmitter Agents; Nuclear Proteins; Pancreatitis; Peptide Fragments; Phenotype; Protein Precursors; Transcription Factors

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

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.

Topics: Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Pancreatitis; Peptide Fragments

The aim of the study was to evaluate the function of pancreatic the B-cell and carbohydrate tolerance after and during pancreatitis. Forty patients (30 men and 10 women) in mean age 41.6 +/- 11.6 years (mean +/- SD) were studied. Analysis of the results was performed in four groups: 1) normal controls, 2) patients after biliary acute pancreatitis (AP) in anamnesis, 3) patients with chronic pancreatitis (ChP) and normal carbohydrate tolerance and 4) patients with chronic pancreatitis and impaired of glucose tolerance (ChP + IGT, WHO classification). Pancreatitic B-cell activity was evaluated by the measurement insulin (IRI) and C-peptide (CP) serum concentrations in fasting state and after 75 g oral glucose and after intravenous glucagon injection (1 mg). Hepatic insulin extraction was estimated from of the serum IRI/CP molar ratio. This study demonstrated impaired function of the pancreatic B-cell in groups after acute pancreatitis and with chronic pancreatitis at normal levels of glycaemia. A progressive reduction of stimulated serum IRI and CP concentrations in groups (2), (3) and (4) was observed. In those groups the increase of serum IRI/CP ratio was found.. Impaired function of the B-cell after pancreatitis is a frequent complication and to improve metabolic control a mechanism of hepatic insulin clearance reduction is involved.

Topics: Adult; C-Peptide; Chronic Disease; Dietary Carbohydrates; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

In a double-blind randomized study, 30 patients received somatostatin infusion during ERCP and 30 patients placebo with the aim of evaluating whether somatostatin can reduce the incidence of injection pancreatitis. S-amylase, U-amylase and S-lipase were evaluated before, during and after (up to 48 hours) ERCP. C-peptide was also determined as a marker of the function of the endocrine pancreas. While no statistically significant effect of somatostatin in terms of amylase and lipase was to be found, somatostatin did significantly decrease c-peptide levels in plasma, indicating that the peptide inhibited beta-cell secretion. About 40% of patients in the somatostatin group and about 50% in the placebo group showed signs of injection pancreatitis (elevated levels of enzymes) and in both groups there are patients with clinically apparent pancreatitis.

Topics: Aged; Amylases; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Double-Blind Method; Female; Humans; Injections; Lipase; Male; Middle Aged; Pancreatitis; Somatostatin

The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Glucagon; Humans; Insulin; Pancreatic Function Tests; Pancreatic Polypeptide; Pancreatin; Pancreatitis

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

Severe insulin resistance syndromes, such as lipodystrophy, lead to diabetes, which is challenging to control. This study explored the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in a series of 12 patients with severe insulin resistance due to partial lipodystrophy.. A retrospective chart review of the safety (N = 22) and efficacy (N = 12) of SGLT2is in patients with partial lipodystrophy was conducted at our institution. The efficacy outcomes included hemoglobin A1C level, insulin dose, fasting plasma glucose level, C-peptide level, lipid profile, 24-hour urinary glucose excretion, estimated glomerular filtration rate, and blood pressure before and after 12 months of SGLT2i treatment.. The hemoglobin A1C level decreased after SGLT2i treatment (at baseline: 9.2% ± 2.0% [77.0 ± 21.9 mmol/mol]; after 12 months: 8.4% ± 1.8% [68.0 ± 19.7 mmol/mol]; P = .028). Significant reductions were also noted in systolic (P = .011) and diastolic blood pressure (P = .013). There was a trend toward a decreased C-peptide level (P = .071). The fasting plasma glucose level, lipid level, and estimated glomerular filtration rate remained unchanged. The adverse effects included extremity pain, hypoglycemia, diabetic ketoacidosis (in a patient who was nonadherent to insulin), pancreatitis (in a patient with prior pancreatitis), and fungal infections.. SGLT2is reduced the hemoglobin A1C level in patients with partial lipodystrophy, with a similar safety profile compared with that in patients with type 2 diabetes. After individual consideration of the risks and benefits of SGLT2is, these may be considered a part of the treatment armamentarium for these rare forms of diabetes, but larger trials are needed to confirm these findings.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucose Transporter Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipodystrophy; Pancreatitis; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors

We aimed to identify clinical characteristics and biochemical parameters at presentation in newly diagnosed children and adolescents with Fibrocalculous pancreatic diabetes (FCPD) and compare them with Type 1 Diabetes (T1D) children.. A retrospective chart review yielded 226 patients (below 18 years) who presented and fulfilled diagnostic criteria of diabetes mellitus. Classification of diabetes was based on American Diabetes Association (ADA), World Health Organization (WHO), International Society for Paediatric and Adolescent Diabetes (ISPAD), and Mohan's criteria and all patients underwent abdominal X-ray.. A total of 31 (13.7%) patients fulfilled criteria of FCPD and 63 (27.9%) of autoantibody positive T1D. When comparing FCPD with T1D at presentation, FCPD patients were older, 14.23 years vs 11.32 years. Fewer FCPD patients presented with Diabetic Ketoacidosis (3.2% vs 34.9%), osmotic symptoms (54.8% vs 93.7%) with significantly longer median duration of symptoms (4.0 vs 1.0 months) and had more abdominal pain (58.06% vs 6.3%) & diarrhoea (38.71% vs 1.6%) as compared to patients with T1D". FCPD patients had higher c-peptide levels (median-0.85 vs 0.61) and required higher mean dose of insulin compared to T1D (1.16 U/kg vs 1.01 U/kg). At presentation fasting plasma glucose was significantly higher in T1D than FCPD, but no difference was noted in post prandial glucose and HbA1c.. There is a significant difference in clinical characteristics and biochemical parameters at presentation between FCPD and T1D patients with a longer symptom duration but insidious course in the former. To the best of our knowledge, this is the first study to report suitable cut-offs for age, c-peptide, duration of symptoms and insulin dose requirement which could be helpful for differentiating FCPD from T1DM patients.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; India; Insulin; Pancreatitis; Retrospective Studies

We report on the transition in blood glucose levels before and after the onset of fulminant type 1 diabetes mellitus in a perinatal woman. In week 38 of pregnancy, before which the patient had normal glucose tolerance, idiopathic acute pancreatitis was diagnosed. Five days thereafter, she became hypoglycemic, so we closely monitored her blood glucose levels. A total of 13 days later, she was hyperglycemic with a blood glucose level >16.0 mmol/L and glycated hemoglobin of 6.4%. Her fasting serum C-peptide reactivity level was 3.6 ng/mL on the 5th day, and 0.2 ng/mL on the 18th day. Multiple insulin injection therapy was administered since the 18th day; after that, ketoacidosis did not occur. The patient was diagnosed with fulminant type 1 diabetes mellitus based on hyperglycemia without high glycated hemoglobin levels and sudden onset insulin-dependent diabetes. Monitoring glucose levels in the case of idiopathic acute pancreatitis during pregnancy and prompt initiation of insulin therapy are important.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Pancreatitis; Pregnancy; Pregnancy Complications

Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing β-cell autoimmunity in susceptible individuals.. We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy.. All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis.. These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of β-cell antigens and neoepitope generation, which are potential initiating events for loss of β-cell self-tolerance.

Topics: Acute Disease; Adolescent; Adult; Autoantibodies; C-Peptide; Child; Child, Preschool; Chronic Disease; Diabetes Mellitus, Type 1; Humans; Infant; Inflammation; Middle Aged; Pancreatitis; Protein Processing, Post-Translational; Recurrence; Risk Factors; Young Adult

Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT).. Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models.. The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint.. Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Topics: Acute Disease; Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Diseases; Middle Aged; Pancreatic Hormones; Pancreatitis; Prediabetic State; Prevalence

Pancreas transplant improves quality of life and survival of patients irrespective of pretransplant C-peptide levels. Our objectives were to examine complications and outcomes in patients without measureable C-peptide (insulin-dependent type 1 diabetes mellitus) and carefully selected patients with measurable C-peptide (insulin-dependent type 2 diabetes mellitus) after pancreas transplant.. We conducted a retrospective analysis to examine the demographic, transplant factors, complications, and outcomes in patients with nondetectable pretransplant C-peptide (insulin-dependent type 1 diabetes mellitus) and patients with detectable pretransplant C-peptide (insulin-dependent type 2 diabetes mellitus).. Of 214 consecutive pancreas transplant procedures over a 12-year period, 112 had pretransplant C-peptide level testing (63 patients with type 1 and 49 with type 2 diabetes mellitus). Patients with type 1 disease were more likely to be female (P = .048), and patients with type 2 disease were more likely to be African American (P < .001) and have undergone previous pancreas transplant (P = .042). We observed no differences in donor factors or posttransplant factors (C-peptide after year 2, glucose, and hemoglobin A1C, except that patients with type 2 disease had more pancreatitis) (P = .036). There were no differences in posttransplant complications; however, patients with type 2 disease had significantly higher BK virus nephropathy (P = .006). There were no differences in outcomes between cohorts (rejection, graft loss, or death; P = not significant).. Pancreas transplant can be performed with excellent and equivalent outcomes in patients with type 1 and carefully selected type 2 diabetes mellitus. Patients with type 2 disease are more likely to have posttransplant pancreatitis and BK virus nephropathy, affecting the net benefit for transplant.

Topics: Adolescent; Adult; Biomarkers; BK Virus; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Immunocompromised Host; Kidney Diseases; Male; Opportunistic Infections; Pancreas Transplantation; Pancreatitis; Polyomavirus Infections; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Tumor Virus Infections; Young Adult

To assess the outcomes of drug therapy (DT) followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.. DT comprised of pancreatic enzymes and anti-oxidants failing which, endotherapy (ET; pancreatic sphincterotomy and stent placement) was done. The frequency of pain, its visual analogue score (VAS), quality of life (QoL), serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET. Response was defined as at least 50% reduction in the severity of pain to below a score of 5.. Of the thirty nine patients analysed, 21 (53.9%) responded to DT and 18 (46.1%) underwent ET. The VAS for pain (7.0 ± 2.0. A standardised protocol of DT, followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis, enhanced QoL and improved pancreatic function.

Topics: Acute Disease; Adolescent; Adult; Antioxidants; C-Peptide; Child; Chronic Disease; Feces; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Pain Management; Pain Measurement; Pancreas; Pancreatitis; Prospective Studies; Quality of Life; Recurrence; Sphincterotomy, Endoscopic; Young Adult

Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation.. We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg).. Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06).. Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.

Topics: Acute Disease; Adult; C-Peptide; Cold Ischemia; Female; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Linear Models; Male; Middle Aged; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Retrospective Studies; Time Factors; Transplantation, Autologous; 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

Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction.. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R.. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP.. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

Topics: Autoimmune Diseases; C-Peptide; Calcinosis; Humans; Pancreas; Pancreatitis; Pancreatitis, Chronic

Defective glucagon secretion during hypoglycemia after islet transplantation has been reported in animals and humans with type 1 diabetes. To ascertain whether this is true of islets from nondiabetic humans, subjects with autoislet transplantation in the intrahepatic site only (TP/IAT-H) or in intrahepatic plus nonhepatic (TP/IAT-H+NH) sites were studied. Glucagon responses were examined during stepped hypoglycemic clamps. Glucagon and symptom responses during hypoglycemia were virtually absent in subjects who received islets in the hepatic site only (glucagon increment over baseline = 1 ± 6, pg/mL, mean ± SE, n = 9, p = ns; symptom score = 1 ± 1, p = ns). When islets were transplanted in both intrahepatic + nonhepatic sites, glucagon and symptom responses were not significantly different than Control Subjects (TP/IAT-H + NH: glucagon increment = 54 ± 14, n = 5; symptom score = 7 ± 3; control glucagon increment = 67 ± 15, n = 5; symptom score = 8 ± 1). In contrast, glucagon responses to intravenous arginine were present in TP/IAT-H recipients (TP/IAT: glucagon response = 37 ± 8, n = 7). Transplantation of a portion of the islets into a nonhepatic site should be seriously considered in TP/IAT to avoid posttransplant abnormalities in glucagon and symptom responses to hypoglycemia.

Topics: Adult; Arginine; Autografts; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatic Diseases; Pancreatic Ducts; Pancreatitis; Treatment Outcome

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP).. Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated.. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time.. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Topics: Acute Disease; Aged; Analysis of Variance; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; China; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Logistic Models; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Predictive Value of Tests; Recovery of Function; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors

Intrahepatic islet transplantation is an experimental therapy for type 1 diabetes. In the present studies, we sought to address the following questions: 1) In humans, do intrahepatic transplanted islets reestablish coordinated puslatile insulin secretion? and 2) To what extent is insulin secreted by intrahepatic transplanted islets delivered to the hepatic sinusoids (therefore effectively restoring a portal mode of insulin delivery) versus delivered to the hepatic central vein (therefore effectively providing a systemic form of insulin delivery)? To address the first question, we examined insulin concentration profiles in the overnight fasting state and during a hyperglycemic clamp ( approximately 150 mg/dl) in 10 recipients of islet transplants and 10 control subjects. To address the second question, we measured first-pass hepatic insulin clearance in two recipients of islet autografts after pancreatectomy for pancreatitis versus five control subjects by direct catheterization of the hepatic vein. We report that coordinate pulsatile insulin secretion is reestablished in islet transplant recipients and that glucose-mediated stimulation of insulin secretion is accomplished by amplification of insulin pulse mass. Direct hepatic catheterization studies revealed that intrahepatic islets in humans do deliver insulin directly to the hepatic sinusoid because approximately 80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Fasting; Female; Glucose; Glucose Clamp Technique; Hepatic Veins; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Male; Middle Aged; Pancreatectomy; Pancreatitis; Periodicity

The goal of this study was to examine the severity of exocrinous and endocrinous pancreatic incompetence, composition of bile acids (BA) and hemostasis state depending on the etiologic form of chronic pancreatitis (CP). The study comprised 76 patients with CP at the age of 33-74 (46 females and 30 males), 20 of them having alcoholic pancreatitis (AP), 26 --biliary pancreatitis (BP), and 30--involutional pancreatitis (IP); 15 people (without any signs of gastrointestinal tract lesions) made up the control group. CP was diagnosed based on clinical data, laboratory and instrumental assessments. Various degrees of severity of exocrinous and endocrinous pancreatic incompetence were revealed depending on the CP etiology. AP patients had more marked alterations of this type depending on the severity and presence of complications. The study revealed changes in the quantitative and qualitative BA composition, which can cause reduced absorption of exogenous cholesterol in the CP patients' bowels and be one of the reasons affecting the exocrinous function of the pancreas. IP patients had more marked alterations of this type. All CP patients had blood hypercoagulation accompanied by a reduction of the public constant of blood coagulation, increase of the coagulation index and clot elasticity. Patients with the complicated course of the disease had more marked alteration of this type.

Topics: Adult; Aged; Bile Acids and Salts; C-Peptide; Cholecystokinin; Chronic Disease; Feces; Female; Homeostasis; Humans; Male; Middle Aged; Pancreas; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis

The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas.. Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period.. Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels.. Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Topics: Aged; Aged, 80 and over; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Humans; Islets of Langerhans Transplantation; Length of Stay; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Transplantation, Autologous; Treatment Outcome

There was a study of 19 chronic pancreatitis patients (10 male and 9 female), 11 chronic pancreatitis and pancreatogenic diabetes mellitus patients (8 male and 3 female) and 12 type 2 diabetes mellitus patients (4 male and 8 female) at the age of 30-60 as well as 15 control group subjects at the same age range. The content of the C-peptide and such peptides as INCINE, PAMG-cine and PAMG-tin in the blood serum was subjected to the immunoradiometric assay. It was discovered that there is a trend to the increased C-peptide level in CP patients while the C-peptide level in CP patients with diabetes mellitus was smaller than that in the control group; the C-peptide level in CP patients with type 2 diabetes mellitus was higher as compared to that in the control group. It was shown that erythrocytes of CP patients are less sensitive to insulin action and do not respond to the presence of insulinomimetic peptides under examination during the glucose uptake test. CP patients with diabetes mellitus and type 2 diabetes mellitus patients are more sensitive to the action of insulin and peptides applied. Synthetic insulinomimetic peptides can serve as a means for discovering the functional cell deficiency under the glucose uptake test.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Erythrocytes; Female; Glucose; Glycodelin; Glycoproteins; Humans; Insulin; Male; Middle Aged; Pancreas; Pancreatitis; Peptides; Pregnancy Proteins

Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes.. Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements.. Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby.. Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.

Topics: Adult; Aged; C-Peptide; Cell Count; Chronic Disease; England; Female; Follow-Up Studies; Glycated Hemoglobin; Hospitals, General; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Organ Size; Pancreatectomy; Pancreatitis; Retrospective Studies; Time Factors; Transplantation, Autologous

Tropical calcific pancreatitis (TCP) is a chronic, nonalcoholic pancreatitis, which is limited to developing countries. In this condition, surgical decompression of the pancreatic duct consistently leads to relief of abdominal pain. However, no data are available on the effect of such intervention on pancreatic function. The aim of the present study was to prospectively evaluate b-cell and exocrine function following ductal drainage in patients with TCP. We studied 14 consecutive TCP patients who underwent ductal decompression for abdominal pain (longitudinal pancreaticojejunostomyin 12 patients, endoscopic sphincterotomy and ductal stenting in 2 subjects). Six patients who refused similar intervention served as controls. Patients were evaluated prospectively (median follow-up 13 months) for pain score, fasting and oral glucose stimulated plasma C-peptide, serum trypsin, and fecal chymotrypsin. After intervention, 1 patient died 2 months after surgery, and 2 others were lost in follow-up. The pain score improved significantly following duct decompression (median 8.0 vs. 0, p < 0.01), while in the control group there was no change in pain score (7.0 vs. 7.0). There was no change in b-cell function after intervention (fasting plasma C-peptide [mean +/- SEM] 0.41 +/- 0.08 vs. 0.42 +/- 0.05 nmol/l; peak plasma C-peptide 2.24 +/- 0.20 vs. 2.32 +/- 0.24 nmol/l). Fecal chymotrypsin was diminished in all patients prior to intervention (1.9 +/- 0.7 U/g), and did not normalize after ductal drainage in any subject. Serum trypsin levels were variable, being elevated in 29% and diminished in 47% of subjects. All 4 subjects with elevated baseline trypsin levels had a sharp fall after intervention (1020 vs. 175 ng/ml). However, serum trypsin did not normalize after ductal drainage in any patient with a diminished baseline value. In conclusion, patients with TCP have significant reduction in abdominal pain after decompression of the main pancreatic duct. However, there is no significant change in b-cell function. A fall in elevated serum trypsin suggests that there may be relief of subclinical inflammation after intervention; however, there is no improvement in exocrine function after a follow-up of 1 year.

Topics: Abdominal Pain; Adult; C-Peptide; Calcinosis; Decompression, Surgical; Female; Follow-Up Studies; Humans; Islets of Langerhans; Male; Pancreas; Pancreatic Ducts; Pancreaticojejunostomy; Pancreatitis; Prospective Studies; Sphincterotomy, Endoscopic; Trypsin

Up-regulation of urea synthesis by amino acids and dietary protein intake may be impaired in patients with chronic pancreatitis (CP) due to the reduced glucagon secretion. Conversely, urea synthesis may be increased as a result of the chronic inflammation. The aims of the study were to determine urea synthesis kinetics in CP patients in relation to glucagon secretion (study I) and during an increase in protein intake (study II).. In study I, urea synthesis rate, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine in 7 CP patients and 5 control subjects on spontaneous protein intake. The functional hepatic nitrogen clearance (FHNC), i.e. urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between urea synthesis rate and plasma alpha -amino nitrogen concentration. In study II, 6 of the patients of study I had urea synthesis and FHNC determined before and after a period of 14 days of supplementation with a protein-enriched liquid (dietary sequence randomized).. Study I: Alanine infusion increased urea synthesis rate by a factor of 10 in the control subjects, and by a factor of 5 in the CP patients (P<0.01). FHNC was 31.9+/-2.4 l/h in the control subjects and 16.5+/-2.0 l/h (P<0.05) in the CP patients. The glucagon response to alanine infusion (AUC) was reduced by 75 % in the CP patients. The reduction in FHNC paralleled the reduced glucagon response (r(2)=0.55, P<0.01). Study II: The spontaneous protein intake was 0.75+/-0.14 g/(kg x day) and increased during the high protein period to 1.77+/-0.12 g/(kg x day). This increased alanine stimulated urea synthesis by a factor of 1.3 (P<0.05), FHNC from 13.5+/-2.6 l/h to 19.4+/-3.1 l/h (P<0.01), and the glucagon response to alanine infusion (AUC) by a factor of 1.8 (P<0.05).. Urea synthesis rate and FHNC are markedly reduced in CP patients. This is associated with, and probably a result of, impaired glucagon secretion, and predicts a lower than normal postprandial hepatic loss of amino nitrogen. An increase in dietary protein intake increases alanine stimulated urea synthesis and FHNC by a mechanism that involves an increase in glucagon. This indicates that the low FHNC during spontaneous protein intake included an adaptation to the low protein intake, effectuated by a further decrease in glucagon secretion.

Topics: Adaptation, Physiological; Adult; Alanine; Blood Glucose; C-Peptide; Chronic Disease; Dietary Proteins; Female; Glucagon; Humans; Insulin; Liver Function Tests; Male; Middle Aged; Nitrogen; Pancreatitis; Urea

To determine the role of islet autoimmunity in the aetiology of different clinical subtypes of diabetes mellitus in young north Indian patients by measuring islet autoantibodies.. In a cross-sectional study, 145 young patients with diabetes (onset < 30 years) were subdivided into the following categories: Type 1 diabetes (n = 83), malnutrition-modulated diabetes mellitus (MMDM, n = 31) and fibro-calculous pancreatic diabetes (FCPD, n = 31). MMDM subjects presented with emaciation and severe insulin-requiring but ketosis-resistant diabetes, while FCPD was associated with idiopathic chronic calcific pancreatitis. Antibodies to glutamic acid decarboxylase (GADA) and IA-2 (IA-2 A) were detected by immunoprecipitation of 35S-labelled recombinant antigens and cytoplasmic islet cell antibody (ICA) by indirect immunofluorescence.. GADA were present in a significant proportion (23%) of patients with MMDM. In contrast, IA-2 A was increased only among patients with Type 1 diabetes (22%), but not MMDM (3%, P < 0.05). Among patients with a duration of diabetes < 2 years, GADA and/or IA-2 A were found in 61% of Type 1 diabetic and 37% of MMDM patients (P < 0.01). MMDM patients who were positive for GADA had a shorter duration of diabetes, but did not differ in their age at onset of diabetes, body mass index, fasting plasma C-peptide, or frequency of thyroid microsomal and parietal cell antibodies. FCPD subjects had the lowest prevalence of autoantibodies: IA-2 and ICA were absent, while GADA were present in 7% (P < 0.05 vs. Type 1 diabetes).. GADA, though not IA-2 A, were present in a substantial proportion of patients with the MMDM variant of diabetes, suggesting that islet autoimmunity may play a role in its pathogenesis. In contrast, none of the islet antibodies was increased in subjects with FCPD, making it likely that it is a secondary type of diabetes.

Topics: Adolescent; Adult; Age of Onset; Autoantibodies; C-Peptide; Calcinosis; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Fluorescent Antibody Technique, Indirect; Glutamate Decarboxylase; Humans; India; Islets of Langerhans; Male; Nutrition Disorders; Pancreatitis

Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving "transient" insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the "gold standard" for monitoring islet autograft function, may require reappraisal.

Topics: C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Graft Survival; Humans; Insulin; Islets of Langerhans Transplantation; Pancreatectomy; Pancreatitis; Proinsulin; Transplantation, Autologous

The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes.. An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis.. The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups.. The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.

Topics: C-Peptide; Case-Control Studies; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis; Peptide Fragments; Protein Precursors; Time Factors

Fibrocalculous pancreatic diabetes (FCPD) is a type of diabetes secondary to tropical chronic non-alcoholic pancreatitis. Little is known about the aetiopathogenesis of FCPD. We studied glutamic acid decarboxylase antibodies (GAD-Ab) and islet cell antibodies (ICA) in patients with FCPD and compared the results with Type 1 (insulin dependent) diabetes mellitus, Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic subjects in Southern India. The prevalence of GAD-Ab was 7.0% (95% Confidence Interval (CI) 1.9-17.2) in FCPD, 47.5% (CI 31.4-64.0) in Type 1 (p < 0.001 compared to FCPD), 5.6% (CI 1.5-13.9) in Type 2 (non-significant (NS) compared to FCPD) and 0% in controls. The prevalence of ICA was 6.3% (CI 1.2-17.4) in FCPD, 53.8% (CI 37.1-70.0) in Type 1 (p < 0.001 compared to FCPD), 9.9% (CI 4.0-19.4) in Type 2 (NS compared to FCPD) and 4.7% (CI 0.4-16.1) in controls. The data suggest that in FCPD, the frequency of auto-antibodies is low and its aetiology is probably not linked to autoimmunity in the majority of the patients.

Topics: Adult; Autoantigens; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; India; Islets of Langerhans; Male; Middle Aged; Pancreatic Diseases; Pancreatitis; Reference Values

The authors compared in seven patients with acute pancreatitis the levels of endogenous somatostatin, insulin and C-peptide to assess their mutual correlation and relation to the development of the disease and serum amalyse levels. The results were compared with values recorded in 11 healthy volunteers. The levels of endogenous somatostatin were in patients with acute pancreatitis significantly higher (p < 0.05) than in the control group. The authors found an inverse relationship between the somatostatin and amylase level (correlation coefficient 0.75). They did not observe a significant correlation between somatostatin and insulin levels nor between somatostatin and C-peptide levels. The elevated somatostatin level may be due to the counteregulatory reaction during secretion, stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).

Topics: Acute Disease; Adult; Amylases; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Somatostatin

Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes).. We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis.. Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied.. The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Topics: Adult; Aged; Amylases; Bicarbonates; C-Peptide; Chronic Disease; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreas; Pancreatitis

The exocrine and endocrine pathophysiology of chronic calcific pancreatitis of the tropics (CCPT) remains elusive. The objective of this study was to evaluate the spectrum and correlates of the exocrine and endocrine pancreatic dysfunction in CCPT. Thirty-seven consecutive patients with a clinico-radiological diagnosis of CCPT were stratified into three subgroups: CCPT-normal glucose tolerance (NGT), CCPT-abnormal glucose tolerance (IGT) and CCPT-diabetes mellitus (DM). Ten ketosis resistant young diabetic (KRDY) patients, 10 classical insulin dependent diabetes mellitus (IDDM) patients and 18 healthy matched controls were included for comparison. Fecal chymotrypsin (FCT) levels and blood C-peptide levels (basal and post i.v. glucagon stimulation) were estimated for assessing the exocrine and endocrine pancreatic functions, respectively. Sonography was performed to evaluate the pancreatic size and ductal diameter. Pancreatic exocrine-endocrine correlation was examined by studying the C-peptide/fecal chymotrypsin ratio (CP/FCT) (CP/FCT of normal controls = 1). Mean FCT levels in all 3 subgroups of CCPT (NGT: 3.4 micrograms/g; IGT: 0.82 microgram/g; DM: 2.4 micrograms/g) were very low (87-96% reduction in exocrine pancreatic dysfunction; mean FCT in healthy controls was 22.8 micrograms/g) (P < 0.0001). In contrast, KRDY and IDDM patients displayed 50-54% reduction in pancreatic acinar function (P < 0.001). Basal and stimulated C-peptide levels progressively fell in the 3 CCPT subsets (NGT: 0.23 and 0.46 > IGT: 0.14 and 0.29 > DM 0.10 and 0.14) (P < 0.01). CCPT patients exhibited pancreatic atrophy and ductal dilation (> 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Analysis of Variance; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Ultrasonography

In 14 patients with acute pancreatitis during 16 episodes of the disease the concentrations of blood glucose, serum insulin (IRI), C-peptide (CP), and proinsulin (Pro) were determined in the fasting state on d 1, 2, 3, 5, and 10 after the attack. The peptides were measured using RIAs, and for determination of CP two antibodies: Byk-Mallinckrodt's and more specific M-1221 Novo antibodies were used. Apart from sporadic rises in the initial period of the disease, the blood glucose level did not change significantly and had a decreasing trend. On d 1 the mean serum IRI level was 0.17 +/- 0.04 (SD) nM, and it decreased on d 5 to 0.06 +/- 0.04 nM, rising again to 0.11 +/- 0.15 nM on d 10. The serum Pro concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8 pM, whereas the serum CP values determined with M-1221 antibodies were 0.48 +/- 0.50, 0.34 +/- 0.19, and 0.52 +/- 0.25 nM, respectively. However, when serum CP was determined using Byk-Mallinckrodt kits, the concentration on d 1 was 1.90 +/- 1.12 nM and over the following days it decreased to 1.08 +/- 0.98 nM on d 5 and on d 10 it was 1.11 +/- 0.46 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; Blood Chemical Analysis; Blood Glucose; Blood Proteins; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Proinsulin; Time Factors

Results of dynamic investigation of beta-endorphins and hormonal state were analysed in 34 patients with pancreonecrosis aged from 23 to 54 years. The dependency of this indexes on the severity of clinical course and presence of complications was determined. The correction ways of injurious action of stress-reaction in pancreonecrosis were proposed.

Topics: Adrenal Cortex Hormones; Adult; C-Peptide; Endorphins; Female; Hormones; Humans; Insulin; Male; Middle Aged; Necrosis; Pancreatitis; Pituitary Hormones; Radioimmunoassay; Stress, Physiological; Thyroid Hormones

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

Topics: Adult; Alcoholism; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Female; Humans; Islets of Langerhans Transplantation; Liver Function Tests; Pancreatectomy; Pancreatitis; Time Factors; Tomography, X-Ray Computed; Transplantation, Autologous

In a prospective clinical-experimental study, 15 consecutive patients with chronic pancreatitis, operated on because of severe pain, were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th day postoperatively, and 3 months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, and pancreatic polypeptide were determined. As indicated by the k value, glucose tolerance improved postoperatively in 10 patients (66.6%); three patients (19.9%) showed no change, and one patient (6.6%) was worse. Only one patient (6.6%) developed evident diabetes mellitus immediately postoperatively. Pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (p < 0.01). The stimulation of pancreatic polypeptide after oral glucose was significantly lower postoperatively (p < 0.01). Duodenum-preserving pancreas head resection does not lead to an impairment of glucose tolerance in the majority of patients; a deterioration was observed only in few cases (13.3%).

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Kinetics; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; Prospective Studies

The examination of 170 patients with chronic alcohol pancreatitis revealed diabetes mellitus (DM) in 21% of them. It manifested with polydipsia, polyuria and weight loss along with pancreatitis symptoms. DM complications were rare. Exercise tests were indicative of reduced insulin and glycagon reserves in the majority of the examinees. This condition depended on pancreatitis severity. DM in pancreatitis presents a high risk of hypoglycemia which should be taken into consideration when designing schemes of relevant treatment.

Topics: Adult; Alcoholism; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Glucose; Humans; Insulin; Islets of Langerhans; Male; Pancreatitis; Time Factors

Plasma lipase, C-peptide reactivity (CPR) and human pancreatic polypeptide (HPP) responses after ingestion of elemental diet were studied in 27 patients with chronic pancreatitis. These subjects were classified into 3 groups according to ERP findings; minimum or mild (MIP, n = 17), moderate (MOP, n = 6) and advanced (ADP, n = 4). Basal plasma lipase levels in the MIP and MOP patients were significantly higher than that in the controls (P < 0.05). Plasma CPR response (sigma delta CPR) in MIP cases were significantly higher than that in controls (P < 0.05). Also, plasma HPP (response (sigma delta HPP) in MIP cases were significantly higher than that in controls (P < 0.05). Plasma CPR and HPP responses correlated with the severity of chronic pancreatitis. Fourteen of the 17 MIP patients (82%) showed higher levels of basal lipase or sigma delta HPP in comparison to the respective normal ranges. This study suggested that the ED test may be more sensitive for detection of mild chronic pancreatitis and that it may be useful for evaluating exocrine and endocrine pancreatic functions in various stages of chronic pancreatitis.

Topics: C-Peptide; Chronic Disease; Female; Food, Formulated; Humans; Lipase; Male; Middle Aged; Pancreatic Function Tests; Pancreatic Polypeptide; Pancreatitis; Radioimmunoassay

14 patients with acute pancreatitis during 16 episodes of the disease were studied. The concentration was measured of blood glucose, serum insulin (IRI), serum C-peptide (CP) using two methods: with Byk-Mallinckrodt kits and with more specific M-1221 antibodies Novo, and of serum proinsulin (Pro) in fasting state on days 1, 2, 3, 5 and 10 after the acute onset. Apart from some sporadic rises in the initial period of the disease, the blood glucose level did not change significantly, and had rather a decreasing trend. The mean serum IRI concentration was 0.17 +/- 0.17 (SD) nmol/l, and it decreased on the 5th day to 0.06 nmol/l 0.04 nmol/l, rising again to 0.11 +/- 0.15 nmol/l on the 10th day. The serum Pro concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8 pmol/l, while the serum CP concentration determined with M-1221 antibodies was 0.48 +/- 0.50, 0.34 +/- 0.19 and 0.52 +/- 0.25 nmol/l respectively. However, when for serum CP determinations the Byk-Mallinckrodt kits were used, the concentration of this peptide was on the 1st day 1.90 +/- 1.12 nmol/l, and it decreased over the following days to 1.08 +/- 0.98 on the 5th day, but remained on the same level on the 10th day (1.11 +/- 0.46 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Proinsulin

Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Fluoresceins; Glucagon; Glucose; Humans; Insulin; Middle Aged; Pancreatitis; Radioimmunoassay; Thyrotropin-Releasing Hormone; Thyroxine

Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

Topics: Adult; Alcoholism; C-Peptide; Ceruletide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Pancreatitis; Secretin

In patients suffering from chronic pancreatitis with concomitant atrophic antral gastritis, gastrinemia is less whereas the response of pancreatic enzymic secretion to pentagastrin is more potent than in patients suffering from chronic pancreatitis without atrophic alterations in the gastroduodenal mucosa. The pancreas-stimulating effect of pentagastrin administered in a dose of 6 micrograms/kg is approximately equal to the action of 0.5 U/kg pancreozymine and noticeably yields to the effect of 1.5 U/kg pancreozymine (according to the criteria for output of intraduodenally secreted lipase and trypsin). The same diagnostic dose of pentagastrin used commonly for gastric secretion studies not only stimulates pancreatic enzyme secretion but also enhances the activity of beta-cells of Langerhans' islets of the pancreas in accordance with insulinemia and blood C-peptide determined by RIA.

Topics: C-Peptide; Cholecystokinin; Chronic Disease; Dose-Response Relationship, Drug; Gastrins; Gastritis, Atrophic; Humans; Insulin; Islets of Langerhans; Pancreas; Pancreatitis; Pentagastrin; Recurrence

The mechanisms of carbohydrate metabolism abnormality were studied in 128 patients suffering from chronic pancreatitis by means of simultaneous measurement in the blood of glucose, insulin, C-peptide and glucagon concentrations both on an empty stomach and after the glucose tolerance test (50 g glucose). Five types of the hormonal mechanisms of hyperglycemia were revealed, caused by derangement of beta-cells for the most part, more rarely by alpha-cells of the pancreas and impairment of interregulation of those cells in chronic pancreatitis. The rate of the hormonal mechanisms of carbohydrate metabolism abnormality was shown to depend on the gravity and duration of chronic pancreatitis whereas blood sugar and insulin response to intravenous injection of glucose in patients with chronic pancreatitis to have characteristic features in common to type I and II diabetes.

Topics: Blood Glucose; C-Peptide; Carbohydrates; Chronic Disease; Glucagon; Humans; Insulin; Islets of Langerhans; Pancreatitis; Radioimmunoassay

Insulinemia, concentration of C-peptide and glucagon in the blood was studied in chronic hepatitis patients showing moderate tolerance disorders to glucose and diabetes mellitus developed against the background of chronic pancreatitis. Both groups showed hyperglucagonemia. Basal hypoinsulinemia and reduction of the C-peptide level revealed only in patients suffering of chronic pancreatitis with secondary diabetes mellitus. Reduced reaction of beta-cells of the pancreas to physiologic stimulation by pancreosozymin were observed also in less significant disorders of tolerance to glucose. The authors discuss the significance of changes in the sequential development of different degrees of disorders of the carbohydrate metabolism in patients with chronic recurrent pancreatitis.

Topics: C-Peptide; Carbohydrate Metabolism; Cholecystokinin; Chronic Disease; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Pancreatitis; Recurrence

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreatitis; Time Factors

Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non-diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous-pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components.

Topics: Adult; Blood Glucose; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; India; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Trypsin

Pharmacological, percutaneous celiac plexus blockade is often inefficient in the treatment of pain in chronic pancreatitis. Lack of efficiency could be due to incomplete denervation of the plexus; however, a method for measuring the completeness of celiac plexus blockade is not yet available. We have, therefore, monitored the physiological completeness of pharmacological percutaneous celiac blockade with 40 ml 25% ethanol by measuring the effect of posture on heart rate, blood pressure, hepato-splanchnic vascular resistance, and pancreatic hormone concentrations before and after celiac plexus block in 6 patients with chronic pancreatitis. Blood pressure decreased and heart rate increased after the block (P less than 0.025), whereas no significant change was found in hepato-splanchnic vascular resistance nor in the change of these parameters during transition from the supine to standing position. Pancreatic hormones (C-peptide, free insulin, glucagon, pancreatic polypeptide and somatostatin) did not change in response to standing, either before or after the block. The cardiovascular variables were normalized the day after the block, and all the patients were in their habitual state regarding pain after 1 week. In conclusion, pancreatic hormone concentrations in response to standing are not useful for monitoring celiac plexus block, whereas heart rate, blood pressure and hepato-splanchnic blood flow may yield useful information. From such measurements it was concluded that permanent denervation of the celiac plexus was not achieved in our patients after injection of 40 ml 25% ethanol.

Topics: Blood Pressure; C-Peptide; Celiac Plexus; Glucagon; Heart Rate; Humans; Insulin; Middle Aged; Palliative Care; Pancreatic Polypeptide; Pancreatitis; Posture; Somatostatin; Vascular Resistance

The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. This observation suggests that the recognition of glucose is more severely affected than that for non-glucose stimulants. To determine whether a similar selective decrease in glucose response was present before the onset of diabetes we studied two groups of non-diabetic identical twins of patients with recently diagnosed Type 1 diabetes: one group with complement-fixing islet cell antibodies who were at high risk of developing diabetes (four of the five have already developed diabetes) and a group without such antibodies at low risk of developing diabetes. In addition, a group of patients with chronic pancreatitis were studied to control for non-specific damage to the B-cell. Responses to i.v. glucose and i.v. glucagon were compared. Patients with chronic pancreatitis has similar responses to both glucose and glucagon and the responses did not differ from control subjects. The B-cells of the immune positive group showed evidence of pathology because the insulin and C-peptide responses to both stimuli were reduced when compared to either their control subjects or the immune negative twin group. However, the B-cell response to both glucose and glucagon in the immune positive twins was similar. Because the B-cell response to glucose was not less than that to glucagon, a selective destruction of the glucose recognition system cannot be a characteristic of all twins throughout the period before they develop Type 1 diabetes.

Topics: Adult; Autoantibodies; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis; Reference Values; Risk Factors; Twins, Monozygotic

In chronic pancreatitis with moderate derangements of carbohydrate tolerance (detected by the double glucose test), the basal concentrations of insulin and C-peptide in blood are normal whereas in patients with secondary diabetes mellitus are lowered. Glucagonemia is increased in patients of both groups. Euphylline (applied as an inhibitor of nucleotide phosphodiesterase), calcium gluconate and the adrenomimetic drug isadrin consistently increased insulinemia and the blood level of C-peptide in patients with chronic pancreatitis both with moderate and appreciable derangements of glucose tolerance. In patients with secondary diabetes that developed in the presence of pancreatitis, these drugs did not influence glucagonemia. The clinical prospects of the making use of the stimulating action of euphylline, calcium gluconate and isadrin on the function of beta-cells of the pancreas in chronic pancreatitis patients are under discussion.

Topics: Aminophylline; C-Peptide; Calcium Gluconate; Chronic Disease; Diabetes Mellitus; Glucagon; Gluconates; Glucose Tolerance Test; Humans; Insulin; Isoproterenol; Pancreas; Pancreatitis; Recurrence

The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsin, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages III-IV) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrine insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas.

Topics: Acute Disease; Antigens, Tumor-Associated, Carbohydrate; C-Peptide; Chronic Disease; Diagnosis, Differential; Fibrin Fibrinogen Degradation Products; Humans; Pancreatic Neoplasms; Pancreatitis; Recurrence; Trypsin

A study of 47 patients suffering of chronic pancreatitis indicates that the phase of exacerbation of the disease first showed changes in the parameters of external secretion while the incretory system of the pancreas, apparently, reveals disorders at a later phase. With the purpose of correction of the hormonal homeostasis it is recommended to use microcrystalline cellulose as an addition to the diet.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Combined Modality Therapy; Humans; Middle Aged; Pancreatitis; Trypsin

Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Food; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreatic Polypeptide; Pancreatitis; Somatostatin

Mumps epidemics are followed by sporadic cases of insulin dependent diabetes mellitus (IDDM). We have studied beta-cell function in 11 subjects who had had a mumps infection. They had no clinical pancreatitis but were selected as they had abnormal pancreas iso-amylase values and/or glucosuria during the mumps virus infection. At the follow-up some years later the subjects were healthy. A few HbA1-values were noted in the upper part of the normal range. Total serum insulin values were normal, but the C-peptide values were low at first follow-up 1-3 years after infection in all but two patients. These values increased in 4/7 patients during the follow-up period but were subnormal in five subjects still 3-6 years after the infection. All five patients had HLA-DR 3 and/or 4. In 7 out of 11 patients islet cell surface antibodies could be demonstrated. Our results indicate that subclinical mumps pancreatitis may initiate a reaction towards the beta-cells recognized as subnormal C-peptide levels several years later in certain patients. This might contribute to manifest IDDM many years after infection.

Topics: Acute Disease; Adult; Autoantibodies; C-Peptide; Follow-Up Studies; HLA-DR Antigens; Humans; Insulin; Islets of Langerhans; Male; Mumps; Pancreatitis

The levels of immunoreactive insulin, C-peptide and insulin containing erythrocytes were studied in 26 patients on the 2nd and 12th day of their stay in hospital. A higher level of C-peptides was found in the patients as compared to healthy subjects. The level of immunoreactive insulin of the patients did not differ significantly from that of healthy subjects. The number of insulin containing erythrocytes in the patients was much lower than in healthy subjects. Their number after therapy did not rise considerably. There was no correlation between these indices.

Topics: C-Peptide; Chronic Disease; Erythrocytes; Humans; Insulin; Insulin Antibodies; Middle Aged; Pancreatitis; Recurrence

The aim of the present study was to evaluate insulin secretion by the pancreatic B cell in a group of patients with severe chronic pancreatitis and without overt diabetes. For this purpose we have measured plasma insulin and C-peptide peripheral levels in the fasting state and after a 100-g oral glucose load in 10 patients with severe chronic pancreatitis and fasting normoglycemia, and in 10 sex-, age-, and weight-matched healthy controls. As compared to normal subjects, patients with chronic pancreatitis showed: (1) significantly higher plasma glucose levels after oral glucose load (area under the plasma glucose curve 1708 +/- 142 vs 1208 +/- 47 mmol/liter X 240 min, P less than 0.005); (2) plasma insulin levels significantly higher at fasting (0.11 +/- 0.008 vs 0.08 +/- 0.005 nmol/liter, P less than 0.01) but not after oral glucose administration (area under the plasma insulin curve 79 +/- 12 vs 88 +/- 16 nmol/liter X 240 min); (3) significantly lower plasma C-peptide concentrations both in the fasting state (0.15 +/- 0.01 vs 0.54 +/- 0.05 nmol/liter, P less than 0.001) and after oral glucose load (area under the plasma C-peptide curve 211 +/- 30 vs 325 +/- 37 nmol/liter X 240 min, P less than 0.05). The finding of diminished plasma C-peptide levels suggests that chronic pancreatitis is associated with an impaired B-cell function even in the absence of overt diabetes. The increased or unchanged plasma insulin levels in spite of decreased plasma C-peptide concentrations indicate that in chronic pancreatitis insulin metabolism is reduced, most likely within the liver.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Fasting; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Pancreatitis; Time Factors

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreatitis

Topics: Adult; C-Peptide; Chronic Disease; Fasting; Food; Glucagon; Humans; Insulin; Middle Aged; Pancreas; Pancreatitis; Trypsin

A possible immunogenetic basis for diabetes in chronic pancreatitis was explored by studying 19 patients with both disorders, most of whom required treatment with insulin. In contrast to patients with insulin-dependent (Type 1) diabetes, patients with diabetes and chronic pancreatitis had residual beta cell function but blunted C-peptide responses to intravenous glucagon, absence of circulating islet cell antibodies, and HLA-DR types similar to control subjects and patients with chronic pancreatitis without diabetes. Diabetes complicating chronic pancreatitis is therefore not associated with the biochemical or immunogenetic markers characteristic of Type 1 diabetes.

Topics: Adult; Aged; Autoantibodies; Blood Glucose; C-Peptide; Chronic Disease; Cytoplasm; Diabetes Mellitus, Type 1; Female; HLA-DR Antigens; Humans; Islets of Langerhans; Male; Middle Aged; Pancreatitis

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

Radioimmunoassay was employed to study blood content of insulin, C-peptide and glucagon in 78 patients with chronic pancreatitis. It was revealed that during exacerbation, there was an increase in the content of insulin and glucagon and, to a lesser degree, in that of C-peptide. During remissions, part of the patients showed insular deficiency which increased with disease standing. When pancreatitis lasted from 1 to 5 years or from 5 to 10 years, diabetes mellitus was recorded in 9.4% of the patients and in 16% of the patients, respectively.

Topics: C-Peptide; Chronic Disease; Glucagon; Humans; Insulin Antibodies; Pancreatic Hormones; Pancreatitis; Radioimmunoassay; Recurrence

In 11 persons with normal pancreas function and 21 patients with chronic pancreatitis serum levels of insulin and C-peptide were measured under basal conditions and after maximal stimulation with glucose-tolbutamide-glucagon. Patients with the highest excretory deficiency in the secretin-pancreozymin test had the most marked impairment in endocrine function. In patients with manifest diabetes the exocrine capacity was reduced to an average of 10% of normal. The endocrine parameters correlated linearly with the exocrine ones, most markedly C-peptide reserve with pancreatic enzyme secretion.

Topics: Adult; C-Peptide; Chronic Disease; Chymotrypsin; Diabetes Mellitus; Female; Humans; Insulin; Male; Pancreas; Pancreatitis; Trypsin

The degree of correlation between exocrine pancreatic function and endocrine secretory capacity was examined in 13 chronic pancreatitis patients with secondary diabetes mellitus, 8 chronic pancreatitis patients without diabetes, and 11 healthy subjects. The two parameters were studied under maximal stimulation (volume-corrected secretin-pancreozym test and glucose-tolbutamide-glucagon provocation, respectively). A close, linear correlation was found between all endocrine variables and pancreatic acinar function (e.g. rs = 0.77 for chymotrypsin output and C-peptide release; p less than 0.0001). The correlation was less strong with pancreatic bicarbonate output (e.g. rs = 0.49 for C-peptide release; p less than 0.05). In our patients, secondary overt diabetes occurred in chronic pancreatitis when protease outputs were, on an average, reduced to about 10% of the mean maximal protease output of normal subjects.

Topics: Adult; C-Peptide; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatic Function Tests; Pancreatic Hormones; Pancreatitis

Endocrine function of the pancreas was examined in patients with chronic pancreatitis of different etiology. Radioimmunoassay was applied to measure blood immunoreactive insulin, C-peptide and glucagon as characteristics of the hormonal activity of the pancreas. Pancreatic function was revealed to be disordered. The degree of the disorders correlated with the disease gravity and duration as well as with its progress (exacerbation or remission). As compared with patients presenting with cholepancreatitis, more remarkable alterations, which were particularly well observable during making the glucose tolerance test, were found in patients with chronic pancreatitis of alcoholic etiology.

Topics: Alcoholism; Blood Glucose; C-Peptide; Chronic Disease; Fatty Liver; Female; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis; Proinsulin

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

Carbohydrate and lipid metabolism were studied in 10 patients who had undergone total pancreatectomy. The results were compared with Type I diabetic patients and normal subjects, all of whom were matched for age, sex and weight. At the same level of glycemic control, the daily need for insulin was significantly lower in the patients with pancreatogenic diabetes than in those with Type I diabetes. Concentrations of serum total VLDL and HDL triglyceride were higher in the pancreatectomized patients than in the diabetic or normal controls, whereas concentrations of serum total and LDL cholesterol were significantly lower. The composition of the VLDL, LDL and HDL particles was abnormal in the totally pancreatectomized patients as all three lipoprotein fractions were enriched in triglyceride. HDL2 cholesterol was similar in the totally pancreatectomized patients to that in the other two groups but HDL3 cholesterol was lower. Postheparin plasma lipoprotein lipase and hepatic lipase activities were normal. It is concluded that in totally pancreatectomized patients the changes in the lipoprotein profile on reflect more the action of various confounding factors, i.e. malabsorption, continuance of alcohol abuse and dietary changes than the impact of the diabetes itself.

Topics: Adult; Blood Glucose; C-Peptide; Carbohydrates; Chronic Disease; Diabetes Mellitus, Type 1; Heparin; Humans; Lipids; Lipoprotein Lipase; Lipoproteins; Liver; Middle Aged; Pancreatectomy; Pancreatitis

Plasma concentrations of pancreatic glucagon, C-peptide, and pancreatic polypeptide were measured during arginine stimulation in 16 patients with chronic pancreatitis, in eight subjects with idiopathic diabetes mellitus, and in seven healthy controls. The hormone responses were compared with exocrine pancreatic function as assessed using the urinary excretion rate of p-aminobenzoic acid after oral ingestion of n-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). The increase in pancreatic glucagon levels during arginine stimulation was significantly reduced in patients with chronic pancreatitis compared to healthy controls, most markedly in those with secondary diabetes. In contrast, the glucagon response was unimpaired in patients with idiopathic diabetes. The arginine-induced increase in plasma glucagon and C-peptide concentrations correlated significantly with urinary PABA excretion in chronic pancreatitis (P less than 0.001, P less than 0.01, respectively). The responses of plasma C-peptide and pancreatic polypeptide separated pancreatitic and idiopathic diabetes less well. Thus, the glucagon response to arginine distinguished secondary diabetes due to chronic pancreatitis and idiopathic diabetes mellitus. The correlation between urinary PABA excretion and glucagon levels suggests that in chronic pancreatitis there is a parallel impairment of exocrine and endocrine function.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Arginine; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; para-Aminobenzoates

Optimum multimodality examination of the pancreas includes sonographic, radioimmunological, scintigraphic and angiographic studies. Sonography is a method of choice to study anatomotopographic features of the pancreas. The radioimmunoassay is intended both for the mass screening of patients with hepatogastro-duodenal diseases and for the differential diagnosis of chronic pancreatitis by the nature and type of disease. The use of pancreatoscintigraphy should be restricted in view of considerable exposure of patients. Angiography and angioscanning should be performed strictly according to indications with suspicion for a pancreatic tumor.

Topics: Antigens, Neoplasm; C-Peptide; Chronic Disease; Diagnosis, Differential; Humans; Insulin; Pancreas; Pancreatic Diseases; Pancreatic Function Tests; Pancreatic Neoplasms; Pancreatitis; Radiography; Radioimmunoassay; Radionuclide Imaging; Trypsin; Ultrasonography

In order to investigate whether a relationship exists between in vivo insulin secretion and islet mass, 8 patients suffering from severe chronic relapsing pancreatitis were studied before and after pancreatectomy by glucose-glucagon-test (per os 1.75 g glucose; i.v. glucagon 0.01 mg/kg b.w.) and by intravenous glucose-tolerance-test (iGTT) (i.v. glucose 0.33 g/kg b.w.). Postoperative in vitro assessments of pancreatic insulin and alpha-amylase content were performed, and morphometric studies were carried out. Patients were characterized by reduced c-peptide secretion when compared with healthy subjects. The c-peptide response to the glucose-glucagon-test correlated well with the morphometrically estimated exocrine and islet tissue mass (P less than 0.05) and with the content of insulin and amylase in the tissue. The findings suggest that in subjects suffering from severe chronic relapsing pancreatitis the maximal insulin response might represent a parameter for the patient's islet mass.

Topics: Adult; Blood Glucose; C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatitis

The effect of mild hypercalcaemia on the growth hormone (GH), C-peptide and glucose responses to arginine infusion in patients with insulin-dependent idiopathic diabetes mellitus (ID) was compared with that observed in patients whose diabetes was secondary to idiopathic haemochromatosis (IH) and chronic pancreatitis (CP). The summated GH responses to arginine infusion alone were similar in all three groups. Mild hypercalcaemia significantly diminished the GH response to arginine in patients with secondary diabetes, but not in those with ID. As the blood glucose and C-peptide responses were similar in the presence of a normal or raised serum calcium, the differences in GH response could not be ascribed to changes in blood glucose levels or to alterations in endogenous insulin release. For reasons as yet unknown, hypercalcaemia appears to have more of a stabilizing effect on the pituitary somatotrophic granules of those with secondary diabetes than in those with ID.

Topics: Adult; Arginine; C-Peptide; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Female; Growth Hormone; Hemochromatosis; Humans; Hypercalcemia; Male; Middle Aged; Pancreatitis

Endoscopic retrograde pancreatography (ERP) was performed in 48 patients who had been hospitalized for pancreatitis. The findings were related to results of oral glucose tolerance tests. Patients with gross changes at ERP tended to have latent or manifest diabetes. In patients with latent or manifest diabetes, the increase in C-peptide after oral glucose was lower than in healthy subjects, while insulin sensitivity, estimated with euglycemic insulin clamp technique, was within the same range as in healthy subjects. It is concluded that gross changes of the pancreatic ducts after pancreatitis are often accompanied by widespread tissue damage leading to deficient B-cell function and decreased glucose tolerance.

Topics: Adult; Aged; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

Insular apparatus function in primary chronic and reactive pancreatitis associated with hepatobiliary pathology was studied in 178 patients by radioimmunoassay. The authors showed typical changes of insulin and C-peptide concentration in the presence of an i.v. glucose tolerance test that make it possible to differentiate in combination with the trypsin concentration in the serum primary and reactive pancreatitis as well as exacerbation and remission stages of the disease.

Topics: C-Peptide; Chronic Disease; Glucose Tolerance Test; Humans; Insulin; Pancreas; Pancreatic Function Tests; Pancreatitis; Radioimmunoassay; Trypsin

In five totally pancreatectomized human subjects the secretion of gut-derived glucagons was stimulated by ingestion of a meal rich in fat and carbohydrates. Glucagon-like immunoreactivity in plasma, measured with an antiserum against the 6-15 sequence, increased fivefold in response to the meal. Glucagon like immunoreactivity measured with a antiserum against the C-terminal sequence was initially normal (12-13 pmol/l), increased slightly (to 20 pmol/l), and then decreased (to approximately 6 pmol/l). The chromatographic profile of glucagon-like immunoreactivity in plasma at maximum stimulation was studied after concentration by affinity chromatography. Both assay systems identified two peaks (at Kd-values of 0.30 and 0.60-0.65, and 0.30 and 0.70, respectively). The position at Kd 0.70 corresponds to that of glucagon 1-29. The same components may be identified in plasma from normal subjects. It is concluded that the human intestine is capable of generating all of the molecular forms of glucagon which normally are present in plasma.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Dietary Carbohydrates; Dietary Fats; Glucagon; Humans; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis

Plasma immunoreactive glucagon, C-peptide and substrates (glucose, lactate, and alanine) were measured in 21 pancreatectomized patients and 28 patients with chronic calcifying pancreatitis during arginine infusion. Results were compared with those obtained in control and in insulin-dependent diabetic subjects, and in pancreatectomized subjects receiving a combined infusion of glucagon and arginine or somatostatin and arginine. Plasma immunoreactive glucagon in the pancreatectomized patients was 230 +/- 26 pg/ml (control subjects 100 +/- 13 pg/ml, p less than 0.001), but was unchanged following arginine or somatostatin. Following ethanol extraction of plasma it became undetectable. Similar results were obtained in patients with chronic pancreatitis. In contrast to the insulin-dependent diabetic subjects, no changes in blood glucose, lactate, and alanine concentrations were found during arginine infusion in the pancreatectomized or pancreatitis patients. Addition of glucagon restored the metabolic response to arginine in the pancreatectomized patients. Our results confirm previous smaller studies that in pancreatectomized patients, A cell function is absent or insignificant.

Topics: Adult; Arginine; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Pancreatectomy; Pancreatic Function Tests; Pancreatitis; Somatostatin

Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The Cc-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88, p less than 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72, p less than 0.001), amylase (r = 0.64, p less than 0.05) and to amylase output (r = 0.64, p less than 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.

Topics: Adult; Aged; Amylases; Bicarbonates; C-Peptide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Humans; Islets of Langerhans; Lipase; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Pancreatitis

Topics: Abdomen, Acute; Acute Disease; Adult; Aged; C-Peptide; Female; Glucagon; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Pancreatitis; Peptides

Topics: Biliary Tract Diseases; C-Peptide; Chronic Disease; Diagnosis, Differential; Humans; Pancreatitis; Peptides; Radionuclide Imaging; Trypsin

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatitis; Transplantation, Autologous; Transplantation, Homologous

Pancreatic-type glucagon (PTG) has been found in the plasma of totally pancreatectomized human beings. Arginine infusion, however, caused no increase in PTG. Pancreas-resected patients had a normal response of PTG to arginine and a subnormal increase in C peptide. Gut glucagon-like immunoreactants (gut GLI) were increased in resected patients and further increased in totally pancreatectomized patients. Gut GLI showed no change during arginine stimulation.

Topics: Adult; Aged; Arginine; C-Peptide; Chronic Disease; Female; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatitis; Peptides; Radioimmunoassay

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

Topics: Adult; Aged; C-Peptide; Chronic Disease; Female; Humans; Male; Middle Aged; Pancreatitis; Peptides

A 36-year-old man suffering from chronic pancreatitis involving the whole organ had total duodenopancreatectomy. The Langerhans' islets were isolated from the extirpated organ and transplanted into the liver via portal artery. Insulin substitution could be lowered from 50 I.U. to 12 I.U. by the 5th post operative day. Repeatedly, raised insulin levels could be verified in response to high blood sugar loads. C-peptide and glucagon were also found. 7 months after transplantation the islets still seem to be functioning.

Topics: Adult; C-Peptide; Chronic Disease; Duodenum; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatitis; Transplantation, Autologous

Topics: C-Peptide; Chronic Disease; Humans; Insulin; Liver Diseases; Pancreatitis; Peptides; Radioimmunoassay