Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunization against extracellular neurotoxic proteins has shown promise in the treatment of several neurodegenerative disorders. We sought to determine whether immunization against mutant huntingtin, the intracellular protein that causes Huntington's disease (HD), could slow disease progression in the HD mouse model HDR6/2. DNA vaccination was used to present the mutant intracellular antigen to the immune system in a physiological context. Assay of a peripheral biomarker, pancreatic insufficiency, was used as an initial test of efficacy. DNA vaccination with a 5' fragment of the HD cDNA prevented development of the HDR6/2 diabetic phenotype. Insulin staining demonstrated that HDR6/2 diabetes may be caused by a severe pancreatic insulin deficiency. Immunoresponsive HDR6/2 mice showed increased insulin staining more closely resembling wild-type levels. These observations suggest that DNA vaccination against toxic intracellular proteins may be therapeutic.
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PMID:DNA vaccination against mutant huntingtin ameliorates the HDR6/2 diabetic phenotype. 1271 97

Chronic pancreatitis is a common cause of exocrine pancreatic insufficiency (EPI) in humans and cats but is rarely recognised in dogs in which pancreatic acinar atrophy (PAA) is reportedly more common. This paper describes four dogs which developed EPI secondary to pancreatitis. Two of the dogs also had diabetes mellitus which developed before EPI. One diabetic dog had concurrent hyperadrenocorticism and was euthanased five months after presentation; the other diabetic dog died 48 months after diagnosis. The remaining dogs were alive 78 and 57 months after diagnosis. The number of affected dogs was comparable to the number of cases of presumed PAA seen over the same time period in the same institution. Chronic pancreatitis may be a more common cause of EPI in dogs than previously assumed and may be under-recognised because of difficulties in diagnosis. The relative importance of chronic pancreatitis as a cause of canine diabetes mellitus remains to be ascertained.
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PMID:Exocrine pancreatic insufficiency as an end stage of pancreatitis in four dogs. 1286 28

Minor degrees of pancreatic insufficiency may go unrecognized. There is a paucity of symptoms and physical findings in mild and moderate degrees of insufficiency and in such circumstances laboratory methods are necessary to determine the presence of insufficiency. The clinical picture when insufficiency is well established may be characterized by loss in weight; vague indigestion; voluminous, light-colored, glistening stools in which fat globulets may be seen; changes in the concentration of pancreatic enzymes in the blood indicative of lowered pancreatic function; diminished amounts of pancreatic enzymes in the duodenal juice, and the related poor digestion of fat and protein in the food. Lowered tolerance of carbohydrate, as found in diabetes mellitus, may or may not be present. The location and character of the disease in the pancreas causing the insufficiency may or may not be apparent.
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PMID:The clinical picture of pancreatic insufficiency. 1298 51

Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19-9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19-9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19-9 levels, but normal levels do not exclude cystic fibrosis.
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PMID:Serum CA 19-9 levels as a diagnostic marker in cystic fibrosis patients with borderline sweat tests. 1459 87

This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg(-1), I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks later, animals were either anaesthetised (1 g kg(-1) urethane; IP) for the measurement of pancreatic juice flow or humanely killed and the pancreas isolated for the measurements of cytosolic Ca2+ and Mg2+ levels. Non-fasting blood glucose levels in control and diabetic rats were 92.40 +/- 2.42 mg dl(-1) (n = 44) and >500 mg dl(-1) (n = 27), respectively. Resting (basal) pancreatic juice flow in control and diabetic anaesthetised rats was 0.56 +/- 0.05 ul min(-1) (n = 10) and 1.28 +/- 0.16 ul min(-1) (n = 8). CCK-8 infusion resulted in a significant (p < 0.05) increase in pancreatic juice flow in control animals compared to a much larger increase in diabetic rats. In contrast, CCK-8 evoked significant (p < 0.05) increases in protein output and amylase secretion in control rats compared to much reduced responses in diabetic animals. Basal [Ca2+]i in control and diabetic fura-2-loaded acinar cells was 109.40 +/- 15.41 nM (n = 15) and 130.62 +/- 17.66 nM (n = 8), respectively. CCK-8 (10(-8)M) induced a peak response of 436.55 +/- 36.54 nM (n = 15) and 409.31 +/- 34.64 nM (n = 8) in control and diabetic cells, respectively. Basal [Mg2+]i in control and diabetic magfura-2-loaded acinar cells was 0.96 +/- 0.06 nM (n = 18) and 0.86 +/- 0.04 nM (n = 10). In the presence of CCK-8 (10(-8)) [Mg2+]i in control and diabetic cells was 0.80 +/- 0.05 nM (n = 18) and 0.60 +/- 0.02 nM (n = 10), respectively. The results indicate that diabetes-induced pancreatic insufficiency may be associated with derangements in cellular Ca2+ and Mg2+ homeostasis.
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PMID:Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced diabetes mellitus in rat: effect of cholecystokinin-octapeptide. 1536 89

A 33 year old female was admitted to the hospital to study aedema and bocio, A nephrotic syndrome was diagnosed and the renal biopsy demonstrated membranous glomerulonephritis, stage II. She was also diagnosed of Hashimoto's autoinmmune thyroiditis: TSH (41.5 uUl/ml), T4 (0.07 ng/dl), antithyroglobuline (1/2560) and antimicrosome (1/6400). Four year latter she was diagnosed of autoinmmune pancreatitis, without evidence of diabetes mellitus or exocrine pancreatic insufficiency. Eight years latter she was diagnosed of primary autoimmune suprarrenal insufficiency: basal cortisol: 2.7 mcg/dl, post ACTH estimulated cortisol: 5.6 mcg/dl, antinuclear antibody (1/160) and antiparietal (1/320). We present a pluriglandular autoimmune syndrome with membranous glomerulonephritis, thyroiditis, pancreatitis and suprarrenal insufficiency. To the best of our knowledge this complex syndrome has not been previously described.
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PMID:[Membranous nephropathy associated to autoimmune thyroiditis, chronic pancreatitis and suprarrenal insufficiency]. 1545

Although the median survival for patients with cystic fibrosis (CF) is 32.9 years, a small group of patients live much longer. We analyzed the genotype and phenotype of CF patients 40 years and older seen between 1992 and 2004 at the National Jewish Medical and Research Center (n = 55). These patients were divided into two groups according to age at diagnosis: an early diagnosis (ED) group, median age at diagnosis 2.0 years (range 0.1-15 years, n = 28), and a late diagnosis (LD) group, median age of diagnosis 48.8 years (range 24-72.8 years, n = 27). Consistent with the hypothesis that the CFTR genotype affects the age at diagnosis, CFTR DeltaF508 homozygous individuals were more common in the ED group. Although patients in the ED group were predominantly male, the majority of LD patients were female. Patients with CF diagnosed late had a significantly lower prevalence of pancreatic insufficiency and CF-related diabetes, and better lung function. Fewer patients in the LD groups were infected with Pseudomonas aeruginosa, whereas a greater percentage had cultures positive for nontuberculous mycobacteria. This is the largest cohort of older patients with CF described to date, and our findings indicate that patients diagnosed as adults differ distinctly from survivors of long-term CF diagnosed as children.
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PMID:Late diagnosis defines a unique population of long-term survivors of cystic fibrosis. 1559 74

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.
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PMID:Follow-up of exocrine pancreatic function in type-1 diabetes mellitus. 1611 44

While selected pancreatic diseases may be best treated by total pancreatectomy (TP), the anticipated sequelae of pancreatic insufficiency make TP an undesirable alternative. Our aim was to determine if patients undergoing TP have a worse quality of life (QoL) than age- and gender-matched controls and poor long-term glycemic control. Ninety-nine patients undergoing TP from 1985 through 2002 were identified. The 34 survivors with no recurrent malignancy were surveyed with the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC PAN 26), and our institutional questionnaire. Operative morbidity and mortality were 32% and 5%, respectively. Three late postoperative deaths (3%) were attributed to hypoglycemia. Of the 34 surviving patients, 27 (79%) agreed to participate at a mean of 7.5 years postoperatively. Seven patients had required 12 hospitalizations for poor glycemic control. Per the SF-36, two domains (role physical and general health) were decreased compared with an age- and gender-matched national population (P < .05). The ADD QoL demonstrated an overall decrease in QoL related specifically to the diabetes mellitus (P < .01), but comparison with insulin-dependent diabetics from other causes showed no significant difference in QoL. The EORTC PAN 26 instrument also showed measurable effects on QoL. Total pancreatectomy can be performed safely. QoL after TP is decreased compared with age- and gender-matched controls but not with diabetes from other causes; however, the changes are not overwhelming. TP should remain a viable option but in selected patients.
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PMID:Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up? 1626 76

Cystic fibrosis is an autosomal recessive disorder affecting about 1/3500 case in France. The disease, that affects all epithelia, is responsible for pulmonary tract infections but also pancreas, gut, liver and genital tract abnormalities. It is linked to CFTR gene mutations, inducing unusually high increase of sodium chloride in sweat, used to track down the illness. deltaF508 CFTR mutation, encountered in 70% of cases, is nearly always associated to pancreatic insufficiency with early-onset lung attack. Around 10% of cystic fibrosis cases, whatever the age, are complicated with partially insulinopenic diabetes, favored by pancreatic fibrosis, while one third of patients shows glucose intolerance. After 20 years old, one third of patients suffers from diabetes and one half after 30 years. Diabetes diagnosis is difficult, and requires the fulfillment of oral glucose tolerance test (OGTT). One glycemia greater or equal to 2 g/l, two hours after a 75 g glucose load, established diabetes diagnosis. Indeed, fasting blood glucose and glycated hemoglobin appear as poor diagnosis markers. Despite histological arguments in favor of the mainly mechanical islet disturbances, an increased prevalence of anti-islets auto-antibodies and an increased frequency of HLA DR3/DR4 have been reported in cystic fibrosis population with glucose tolerance troubles. Also, glucose metabolism is influenced by specific factors linked to cystic fibrosis (infection, malnutrition, steroids...). In reason of the silent phase of diabetes, systematic tracking down of diabetes with a yearly OGTT is recommended, all the more so that hyperglycemia appears as a worsening factor of cystic fibrosis. The efficacy of oral anti-diabetic drugs has not been evaluated on large studies. By contrast, some studies argue for insulin therapy as soon as diabetes appears, insulin improving respiratory and nutritional prognosis. In conclusion, the aim of treatment of cystic fibrosis is to prevent the lung function decline by controlling inflammation and infection, to implement endo- and exo-crine pancreas insufficiency, and to improve nutritional status.
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PMID:[Cystic fibrosis diabetes in adult]. 1639 85


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