Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine insufficiency. (1/19)

OBJECTIVE: To examine the feasibility and significance of 13C-Hiolein breath test in evaluating chronic pancreatitis-related exocrine insufficiency and efficacy of enzyme treatment. METHODS: The 13C-Hiolein breath test was used in 8 healthy volunteers (group 1), 8 chronic pancreatitis (CP) patients without steatorrhea (group 2), and 8 CP patients with steatorrhea (group 3). To evaluate the function of pancreatic exocrine, 13CO2 was determined following 13C-Hiolein diet. The 13C-Hiolein test was repeated in group 3 after enzyme supplement therapy. RESULTS: Administration of 13C-Hiolein diet resulted in significantly higher cumulative percent dose of 13C recovery per 6 h (cPDR/6 h) and maximal PDR (PDR(peak)) in the healthy controls (group 1) than the CP patients with steatorrhea (group 3) (11.22%+/-1.22% and 6.11%+/-0.59% vs 2.87%+/-0.73% and 1.53%+/-0.36%, respectively, both P<0.01). In the CP patients with steatorrhea (group 3), a repeated test after enzyme supplementation therapy showed a significant elevation of both cPDR/6 h and PDR(peak) (9.03%+/-0.84% and 2.33%+/-0.47%, both P<0.01 compared with those before enzyme treatment), but cPDR/6 h remained significantly lower than that in the healthy volunteers (group 1, P<0.05). Both cPDR and PDR(peak) in the CP patients without steatorrhea (group 2) were similar to those in the healthy controls (group 1, both P>0.05). CONCLUSION: The results of 13C-Hiolein breath test well reflect fat metabolism status in CP patients, and the test can be used to monitor the efficacy of pancreatic enzymes therapy.  (+info)

Metformin in the treatment of patients with non-alcoholic steatohepatitis. (2/19)

BACKGROUND: Increased insulin resistance is the major pathogenic mechanism in the development of non-alcoholic steatohepatitis. AIM: To investigate the therapeutic effect of metformin, a well-known insulin-sensitizing agent, in the treatment of non-alcoholic steatohepatitis. METHODS: Thirty-six patients with non-alcoholic steatohepatitis were randomized into two groups. The first group was given lipid and calorie-restricted dietary treatment alone, and the second group was given metformin 850 mg b.d. plus dietary treatment, for 6 months. The changes in biochemical, sonographic and histological parameters were compared. RESULTS: The mean serum alanine/aspartate aminotransferase, insulin and C-peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin. The mean changes in these parameters in the metformin group were significantly greater than those in the group given dietary treatment alone. Although more patients in the metformin group showed improvement in the necro-inflammatory activity, compared with the group given dietary treatment alone, no significant differences in necro-inflammatory activity or fibrosis were seen between the groups. CONCLUSION: The data suggest that improvement of the insulin sensitivity with metformin may improve the liver disease in patients with non-alcoholic steatohepatitis.  (+info)

Faecal elastase-I: helpful in analysing steatorrhoea? (3/19)

BACKGROUND: The faecal elastase-1 test (FE-1) is considered easy to perform and sensitive to detect severe and moderate exocrine pancreatic insufficiency. However, little information is available on the specificity of this test in the analysis of steatorrhoea. Our aim was to evaluate the clinical value of FE-1 in the analysis of patients sent in for faecal fat determination. METHODS: Stool samples were collected over 24 hours in 40 healthy controls and 119 patients: 58 patients with chronic pancreatitis and 61 nonpancreatic disease patients with chronic diarrhoea. Faecal fat excretion was determined and FE-1 was measured using a commercially available ELISA kit, which employs two monoclonal antibodies to bind to two distinct epitopes of human pancreatic elastase-1. RESULTS: Faecal elastase-1 test shows good reproducibility. The test lacks sensitivity in detecting exocrine pancreatic insufficiency and chronic pancreatitis (68 and 59%, respectively). However, it is specific with respect to differentiating pancreatic from nonpancreatic causes in patients with steatorrhoea. CONCLUSION: FE-1 lacks sensitivity to detect chronic pancreatitis. It can serve as a simple, noninvasive method to determine the aetiology of steatorrhoea.  (+info)

Phenotypic and genetic characterization of patients with features of "nonclassic" forms of cystic fibrosis. (4/19)

OBJECTIVE: To determine which features of incomplete or "nonclassic" forms of cystic fibrosis (CF) are associated with deleterious CF transmembrane conductance regulator gene ( CFTR ) mutations, and to explore other etiologies for features not associated with deleterious CFTR mutations. STUDY DESIGN: Clinical features were compared between 57 patients with deleterious mutations in each CFTR and 63 with no deleterious mutations. The Shwachman Bodian Diamond syndrome gene ( SBDS ) was sequenced to search for mutations in patients with no deleterious CFTR mutations and steatorrhea to determine if any had unrecognized Shwachman-Diamond syndrome (SDS). RESULTS: The presence of a common CF-causing mutation, absence of the vas deferens, and Pseudomona aeruginosa in the sputum correlated with the presence of two deleterious CFTR mutations, whereas sweat chloride concentration, diagnostic criteria for CF, and steatorrhea did not. However, sweat chloride concentration correlated with CFTR mutation status in patients infected with P aeruginosa. One patient had disease-causing mutations in each SBDS . CONCLUSIONS: Presence of a common CF-causing mutation, absence of the vas deferens and/or P aeruginosa infection in a patient with features of nonclassic CF are predictive of deleterious mutations in each CFTR , whereas steatorrhea in the same context is likely to have etiologies other than CF transmembrane conductance regulator (CFTR) dysfunction.  (+info)

Does the pancreas really produce much more lipase than required for fat digestion? (5/19)

Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4) in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion. This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.  (+info)

Unresponsive or non-compliant steatorrhea in cystic fibrosis? (6/19)

In 105 pancreatic insufficient CF patients (steatorrhea and low fecal elastase-1 concentrations), the effectiveness of pancreatic enzyme therapy (PET) has been assessed (fecal fat losses and coefficient of fat reabsorption). Eight unresponsive subjects were checked for PET compliance with fecal chymotrypsin assay. Three patients were documented to be non-compliant. Unresponsive patients should undergo evaluation for PET compliance.  (+info)

Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. (7/19)

We aimed to investigate how assimilation of nutrients affects the postprandial responses of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and to evaluate the effect of pancreatic enzyme substitution (PES) on insulin secretion in patients with chronic pancreatitis (CP) and pancreatic exocrine insufficiency (PEI). Eight male patients with CP and PEI were studied. Blood was sampled frequently on two separate days after ingestion of a liquid meal with and without PES, respectively. Eight healthy male subjects served as a control group. beta-Cell responsiveness was estimated as changes in insulin secretion rates in response to changes in postprandial plasma glucose (PG). There was no difference in the PG incremental area under curve (AUC) for patients with and without PES [406 +/- 100 vs. 425 +/- 80 mM.4 h (mean +/- SE), P = 0.8]. The response of total GLP-1 was higher after PES (AUC: 7.8 +/- 1.2 vs. 5.3 +/- 0.6 nM.4 h, P = 0.01), as was the response of total GIP (AUC: 32.7 +/- 7.5 vs. 21.1 +/- 8.3 nM.4 h, P = 0.01). Concurrently, both plasma insulin, plasma C-peptide, and total insulin secretion increased after PES (AUC: 17.7 +/- 4.2 vs. 13.6 +/- 2.9 nM.4 h, P = 0.02; 237 +/- 31.4 vs. 200 +/- 27.4 nM.4 h, P = 0.005; and 595 +/- 82 vs. 497 +/- 80 pmol.kg(-1).4 h, P = 0.01, respectively). beta-Cell responsiveness to glucose was not significantly different on the two study days for patients with CP. These results suggest that the secretion of GLP-1 and GIP is under influence of the digestion and absorption of nutrients in the small intestine and that PES increases insulin secretion.  (+info)

Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse. (8/19)

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-(14)C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.  (+info)