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In the majority of patients suffering from chronic pancreatitis an endocrine pancreatic insufficiency is correlated with exocrine dysfunction. The prevalence of impaired or diabetic glucose tolerance is 40-70%, half of these patients suffer from an insulin-dependent diabetes mellitus. In general the probability of endocrine insufficiency progressively increases within the ten years following diagnosis of chronic pancreatitis. Onset and severity of the endocrine dysfunction depend on parenchymal destruction of the pancreas but are also influenced by ongoing alcohol consumption. Pathological findings in the endocrine pancreas are a loss of B-cells with decrease in secretion of insulin but also a loss of B-cell responsiveness to glucose by impaired perisinusoidal diffusion. Disturbances of the enteroinsulinar axis with diminished levels of incretins due to an exocrine insufficiency are also discussed. In addition, an impaired A-cell function may be important, that is characterized by diminished levels of stimulated glucagon. Increased plasma levels of somatostatin were found, the source of which is unknown. The susceptibility to severe hypoglycemia in patients with diabetes mellitus secondary to chronic pancreatitis is higher than in Type I diabetics. This is mainly caused by the impaired glucagon secretion but also influenced by malnutrition and concomitant hepatic dysfunction due to the toxic affect of alcohol. Diagnostic procedures are the measurement of C-peptide-concentrations and profiles of blood glucose after fasting and stimulation with L-arginine or glucose. Especially in the beginning of the endocrine insufficiency the determination of basal levels of blood glucose or C-peptide are not useful. Unless treatment by diet is effective, the therapy of diabetes secondary to chronic pancreatitis should be done by insulin replacement. A certain degree of hyperglycemia may be tolerated due to the risk of hypoglycemia and the persistent alcohol consumption in these patients. Intensified insulin therapy should only be done in selected patients with good compliance. Long-term complications in patients with pancreatogenic diabetes are comparable to diabetes Type I and largely depend on the duration of the diabetes. Life expectancy is reduced, death in these patients is mainly due to persistent alcohol and nicotine abuse (cardiovascular disease, malignant tumors, etc.), in only a minority pancreatitis or diabetes (mainly hypoglycaemia) are relevant risk factors.
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PMID:[Secondary diabetes in chronic pancreatitis]. 1044 9

To investigate the pancreatic exocrine function in noninsulin-dependent diabetes mellitus (type 2 DM), we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 13 healthy control subjects and 22 patients with type 2 DM who had no evidence of pancreatic disease. Samples of pancreatic juices were collected in six fractions for 30 minutes at 5-minute intervals after an intravenous bolus injection of secretin (0.25 CU/kg) and cholecystokinin-8 (CCK) (40 ng/kg). The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose (50%, 40 mL) were measured. The levels of plasma insulin and C-peptide levels in type 2 DM were the same as in healthy controls in the basal state but did not further increase in response to an intravenous glucose. This suggested that patients with type 2 DM had insulin secretion defect rather than insulin deficiency. Pancreatic secretions including volume, bicarbonate, and protein output in response to stimulation with secretin, and CCK were significantly reduced when compared to the healthy controls. We conclude that patients with type 2 DM exhibit impairment of pancreatic exocrine secretion and that this impairment might not be related to insulin deficiency. Therefore, we recommended that careful evaluation for exocrine pancreatic function in type 2 diabetics who have any clinically suspicious symptoms of pancreatic insufficiency.
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PMID:Evaluation of pancreatic exocrine function using pure pancreatic juice in noninsulin-dependent diabetes mellitus. 1091 77

The history of a 45-year-old male type 1 diabetic patient is presented. At the age of 29 years, he was diagnosed to have an autoimmune hepatitis with incipient liver cirrhosis. Five years later, a successful liver/pancreas transplantation was performed. Eighteen months later, however, pancreatic insufficiency occurred due to thrombosis of the pancreatic graft. Besides these conditions, iron deficiency, pernicious anemia, and autoimmune gastritis were also diagnosed. Serum parietal cell antibodies (PCA) and intrinsic factor antibodies (AIF) were positive. At 45, this patient was found to have a gastric carcinoid tumor. The clinical importance of PCA is discussed with regard to chronic atrophic gastritis and pernicious anemia, which both predispose toward gastric carcinoid tumors. Autoimmune type 1 diabetic patients who have a high prevalence of PCA should be screened for gastric autoimmune manifestations and tumors, as the history of this patient illustrates.
J Diabetes Complications
PMID:Autoimmune hepatitis, autoimmune gastritis, and gastric carcinoid in a type 1 diabetic patient: a case report. 1095 74

Abnormality of pancreatic exocrine secretion has been observed in patients with diabetes mellitus. Troglitazone is a novel insulin-sensitizing agent that improves hyperglycemia and hyperinsulinemia in insulin-resistant diabetes mellitus. We investigated the effect of troglitazone on exocrine pancreas in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by intraperitoneal injection of STZ (25 mg/kg), and then 0.2% troglitazone containing rat chow was given for 2 weeks. Control diabetic animals received normal rat chow for 2 weeks. Glucose tolerance tests were performed before and after the administration of troglitazone. Pancreas weight, enzyme, protein, and insulin contents in the pancreas were measured. For the exocrine secretory study, pure pancreatic juice was collected hourly. Plasma glucose concentrations stimulated by the oral administration of 2.5 g/kg glucose in the troglitazone-treated group were significantly lower than those in the control group, but not plasma insulin concentrations. Pancreas weight in diabetic rats was less than that in normal rats. Administration of troglitazone resulted in a significant increase in pancreas weight and amylase and trypsin output. However, protein and insulin contents were not affected by the treatment with troglitazone. Both basal and cholecystokinin (CCK-8; 26 pmol/kg/h) stimulated exocrine secretion in juice volume, amylase, and trypsin output were markedly decreased in diabetic rats, compared with those in normal rats. Impaired basal and CCK-stimulated pancreatic exocrine secretion in diabetic rats recovered to the normal levels when troglitazone was given. In conclusion, troglitazone might be effective to restore exocrine pancreatic insufficiency in STZ-diabetic rats.
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PMID:Effect of troglitazone on exocrine pancreas in rats with streptozotocin-induced diabetes mellitus. 1107 98

We have studied the characteristics of 202 cystic fibrosis adult patients, all with chronic respiratory symptoms, with a median age of 27 yrs (18 to 55 yrs) and a male predominance (56%). At genetic analysis, delta F508 homozygotes were 41%, delta F508 heterozygotes 42% and 17% had no delta F508. The respiratory disease was more severe and complications were more frequent in adults: hemoptysis in 14%, pneumothorax in 15%, lung transplantation in 25 patients. Chronic bronchial colonisation with Pseudomonas aeruginosa, in 76% of patients, contributed to making treatments more severe because of antibiotic i.v. courses and nebulised antibiotics. Respiratory function showed a mean FVC of 62 +/- 22% and a mean FEVI of 48 +/- 94%. External pancreatic insufficiency was found in 83%, diabetes in 14%. Intestinal occlusion syndromes were observed in 11% of patients and hepatic cirrhosis in 8%. In spite of the severity of the respiratory disease, theses patients succeeded in social and occupational insertion; 62% were independent, 18% had children and 77% were working or studying. Analysis of the patients according to age at diagnosis showed that, in 38 patients diagnosed after the age of 18 yrs, the respiratory disease was less severe, pancreatic insufficiency and non-respiratory complications were less frequent (34% had pancreatic insufficiency, 5% had diabetes and none had cirrhosis). This may partly be due to the presence of milder CFTR mutations. In conclusion, cystic fibrosis in adulthood frequently looks like an evolutive form of cystic fibrosis in childhood. Nevertheless, some late diagnosed forms in adults, with better prognosis, have been recently identified.
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PMID:[Characteristics and specificities of cystic fibrosis in adults: evolutive disease of childhood or recently diagnosed disease?]. 1107 85

As their life expectancy has improved, patients with cystic fibrosis have experienced an increasing incidence of diabetes. Diabetes mellitus is characterized by improved and delayed insulin secretion, normal insulin sensitivity, and it is most often accompanied by exocrine pancreatic insufficiency. The development of diabetes mellitus is insidious and symptomless, and the overall cystic fibrosis status deteriorate for years prior to the diagnosis of diabetes. Since insulin therapy seems to revert deterioration for years of clinical status, and since late diabetic complications may develop, diabetes mellitus in cystic fibrosis should be identified by screening with an OGTT from the age of 15 years, and treated with insulin from the time of diagnosis of diabetes.
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PMID:[Diagnosis and treatment of diabetes in adult patients with cystic fibrosis]. 1107 89

We report on a 33-year-old patient from Sri Lanka who had been suffering from recurrent episodes of abdominal cramps since he was ten years old. He additionally suffered from postprandial flatulence and an increased frequency of bowel movements. By the age of 24, his condition had worsened with polyuria and polydipsia and he was diagnosed with type II diabetes mellitus. Recently, the patient's compliance deteriorated steadily and his diabetes mellitus was uncontrolled. His flatulence continued and he had six to seven bowel movements daily. He presented to us with renewed bouts of severe stomach cramps, similar to the painful episodes that the patient experienced in his youth. After exclusion of other etiologies and judging by the clinical picture, the patient's origin and the sonographically and radiologically verified pancreatic calcification, we rendered the diagnosis of a tropic calcifying pancreatitis with secondary diabetes mellitus. According to the literature, malignant neoplasia may develop on the basis of this disease. However, we were able to rule out a carcinoma as the cause of the current pain episodes in this patient based on clinical findings and course. We attributed the stomach cramps to compression of the common bile duct by the fibrotic head of pancreas. Pain and cholestasis regressed, thus obviating the need for surgical intervention (pancreaticojejunostomy). On therapy with enzyme substitution and insulin, the patient's exo- and endocrine pancreatic insufficiency was asymptomatic.
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PMID:[Chronic abdominal pain in a young diabetic patient]. 1111 10

Abnormal glucose tolerance and diabetes mellitus are a common complication of cystic fibrosis (CF). Cystic fibrosis related diabetes (CFRD) is due to decreased insulin secretion, secondary to pancreatic insufficiency. Patients with CFRD have increased morbidity and mortality and are subject to the same microvascular complications as patients with other types of diabetes. Prompt diagnosis and aggressive management of CFRD is important.A consensus conference on CFRD was held in Madrid in May 2000to define the current standards for the diagnosis and management of this disease in Spain.
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PMID:[Consensus on the diagnosis and management of changes in carbohydrate metabolism in cystic fibrosis]. 1114 56

SUMMARY. By August 1997, 11,749 patients with cystic fibrosis had been enrolled in the European Epidemiologic Registry of Cystic Fibrosis (ERCF). Genotype analysis had been performed on 8,963 (76%) of these patients, and the majority had one or two identifiable mutations. Patients with known mutations were classified according to the type of mutation (Classes I-V), and were grouped according to the class of mutation on both chromosomes. This resulted in six subgroups, including all patients homozygous for Class I (I/I, n = 72), for Class II (II/II, n = 5,020), and for Class III mutations, (III/III, n = 23). Since there were only 23 patients homozygous for Class III mutations, a fourth group was made up of patients who were compound heterozygous for a Class II and III mutation (II/III, n = 265). There were only five patients homozygous for Class IV mutations, and consequently a fifth group was made up of all patients carrying at least one Class IV mutation, regardless of the nature of the mutation on the other chromosome (IV/any, n = 187). None were homozygous for Class V mutations; consequently, a sixth group consisted of patients carrying at least one Class V mutation (V/any, n = 22). Mean age was highest in groups III/III, IV/any, and V/any (15.6, 16, and 17 years, respectively) as opposed to 12.4 years in group II/II and 13.4 in group II/III, but both group III/III and V/any were small, and the confidence interval of the mean was large. The percentage of patients receiving pancreatic enzymes was lower in groups IV/any and V/any than in any of the other groups, i.e., approximately 50% of patients 18 years or older in both groups as opposed to between 90-100% of all other patients regardless of age. The prevalence of diabetes mellitus increased with age from 2.6% in patients < 18 years to 22.1% in patients 18 years or older in the large group II/II, but was only 1.5% in patients 18 years or older in group IV/any. Disregarding the small group III/III, abnormally elevated liver enzymes and/or bilirubin (1.5 x upper normal limit) was much less frequent in group IV/any than in any of the other groups, both overall and in patients aged 18 years or more. The course of lung disease appeared to be less dependent on genotype than pancreatic function, with only minor differences between groups; however, the mean values of both FVC % and FEV(1) % were slightly higher in group IV/any than all other groups in both younger and older patients. The same was found for the prevalence of some major clinical signs of severe lung disease, such as clubbing, hyperinflation, and crepitations. Overall mean weight expressed as an age percentile was markedly higher in group IV/any than in any other group, which may be related to the finding of a much lower prevalence of chronic P. aeruginosa infection in patients 18 years or older belonging to group IV/any (and V/any) than in any other group. In conclusion, the presence of a class IV mutation appears to offer some degree of protection against pancreatic insufficiency, diabetes mellitus, and liver disease. We confirmed that lung disease follows a milder clinical course in patients with a class IV mutation and that the presence of a class IV mutation (and possibly class V) is associated with a delay in the onset of P. aeruginosa infection.
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PMID:European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations. 1118 Jun 68

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 patients with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenetic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.
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PMID:Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus. 1127 9


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