Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC) in patients with diabetes mellitus

<p>Abstract</p> <p>Objective</p> <p>Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus.</p> <p>Methods</p> <p>The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation.</p> <p>Results</p> <p>FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%).</p> <p>Conclusions</p> <p>Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.</p

Higher mortality of patients on haemodialysis with pancreatic diabetes compared to type 2-diabetes

In rare cases (1-8%) diabetic patients with end-stage renal disease (ESRD) suffer from diabetic nephropathy (dNP) due to pancreatic diabetes mellitus (PDM). Aim of this study was to investigate differences in the outcome of patients with PDM and those with type 2 diabetes

Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study

The measurement of faecal tumour M2 pyruvate kinase (tumour M2 PK) has been proposed as a novel approach for early detection of colorectal cancer (CRC). However, as regards the potential of the test to detect precursors to CRC, an issue that is highly relevant to estimate its use in reducing CRC incidence and mortality, the available evidence is scant and controversial. The aim of our study was to determine the performance characteristics of the tumour M2 PK test with respect to colorectal adenomas in the target population of screening. Among 1082 participants of screening colonoscopy in Germany, of whom 30% had any adenoma and 10% had an advanced adenoma, the median (interquartile range) tumour M2 PK level in the whole study population was 1.3 U ml−1 (0.3–3.3). At a cutoff value of 4 U ml−1, sensitivity was 22 and 23% for detection of advanced and other adenomas, respectively, whereas specificity was 82%. The area under the receiver-operating characteristics curve (95% confidence interval) was 0.54 (0.51–0.58) and 0.56 (0.52–0.59) for advanced and other adenomas, respectively. In conclusion, the tumour M2 PK test has only very limited potential to distinguish between people bearing precursors to CRC and people with no finding at colonoscopy

Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin

Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times. Cancer cell metabolism, characterized by enhanced glucose uptake, production of lactate and anabolism is considered an ideal target for therapeutic interventions. Expression of PKM2 switches metabolism in favor of cancer cells, therefore, the present study was designed to investigate the hitherto unknown effect of resveratrol, a phytoalexin, on PKM2 expression and resultant implications on cancer metabolism. We observed that resveratrol down-regulated PKM2 expression by inhibiting mTOR signaling and suppressed cancer metabolism, adjudged by decreased glucose uptake, lactate production (aerobic glycolysis) and reduced anabolism (macromolecule synthesis) in various cancer cell lines. A contingent decrease in intracellular levels of ribose-5-phosphate (R5P), a critical intermediate of pentose phosphate pathway, accounted for a reduced anabolism. Consequently, the state of suppressed cancer metabolism resulted in decreased cellular proliferation. Interestingly, shRNA-mediated silencing of PKM2 inhibited glucose uptake and lactate production, providing evidence for the critical role of PKM2 and its mediation in the observed effects of resveratrol on cancer metabolism. Further, an over-expression of PKM2 abolished the observed effects of resveratrol, signifying the role of PKM2 downregulation as a critical function of resveratrol. The study reports a novel PKM2-mediated effect of resveratrol on cancer metabolism and provides a new dimension to its therapeutic potential

Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

Background - Structural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus. Methods - A total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years) were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31); 70-79 years old (n = 38) and over 80 years old (n = 37). 53 young subjects (20-28 years old) were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1. Results - Fecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P < 0.001) and were significantly lower among subjects over 70 years old compared to controls (controls vs. 70-79 years old and controls vs. over 80 years old, both P < 0.001). Among the over 60 years old subjects, the fecal elastase-1 concentrations were below the cut off level of 200 μg/g in 23 of 106 (21.7%) individuals [mean 112 (86-138) μg/g] indicating pancreatic exocrine insufficiency. Of those, 9 subjects had fecal elastase-1 level below 100 μg/g as a marker of severe pancreatic insufficiency. Conclusion - In our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.peerReviewe

Tumour M2-PK as a stool marker for colorectal cancer: comparative analysis in a large sample of unselected older adults vs colorectal cancer patients

Stool testing based on tumour-derived markers might offer a promising approach for non-invasive colorectal cancer (CRC) screening. The aim of this study was to estimate the potential of a new test for faecal tumour M2-PK to discriminate patients with CRC from a large sample of unselected older adults. Faecal tumour M2-PK concentrations were determined in 65 CRC patients and in a population-based sample of 917 older adults (median age: 65 and 62 years, respectively). Sensitivity and specificity of the test were calculated at different cutoff values, and receiver-operating characteristic curves (ROC) were constructed to visualise the discriminatory power of the test. The median (interquartile range) faecal tumour M2-PK concentration was 8.6 U ml−1 (2.8–18.0) among CRC patients and <2 U ml−1 (<2–3.2; P<0.0001) in the population sample. At a cutoff value of 4 U ml−1, sensitivity (95% confidence interval) was 85% (65–96%) for colon cancer and 56% (41–74%) for rectum cancer. Specificity (95% confidence interval) was estimated to be 79% (76–81%). Given the comparatively high sensitivity of the tumour M2-PK stool test (especially for colon cancer) and its simple analysis, the potential use of the test for early detection of CRC merits further investigation. Possibilities to enhance specificity of the test should be explored

Gallstones, cholecystectomy, and the risk for developing pancreatic cancer

We examined the relation between gallstones, cholecystectomy, and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 104 856 women and 48 928 men without cancer at baseline, we documented 349 cases of pancreatic cancer during up to 16 years of follow-up. Participants were classified according to a history of gallstones or cholecystectomy. The age-adjusted relative risk of pancreatic cancer following cholecystectomy or diagnosis of gallstones was 1.31 (95% CI, 0.93–1.83). However, adjustment for other pancreatic cancer risk factors attenuated the association (RR=1.11, 95% CI, 0.78–1.56); this risk did not increase with increasing time following cholecystectomy or gallstones. Gallstones or cholecystectomy do not appear to be significant risk factors for pancreatic cancer

A Functional Proteomic Method for Biomarker Discovery

The sequencing of the human genome holds out the hope for personalized medicine, but it is clear that analysis of DNA or RNA content alone is not sufficient to understand most disease processes. Proteomic strategies that allow unbiased identification of proteins and their post-transcriptional and -translation modifications are an essential complement to genomic strategies. However, the enormity of the proteome and limitations in proteomic methods make it difficult to determine the targets that are particularly relevant to human disease. Methods are therefore needed that allow rational identification of targets based on function and relevance to disease. Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest, such as tumors. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. Here we report an easy, robust and generally applicable approach in which phage particles bearing cell- or tissue-specific peptides serve directly as the affinity probes for their molecular targets. For proof of principle, the method successfully identified molecular binding partners, three of them novel, for 15 peptides specific for pancreatic cancer