Increased insulin resistance and beta cell activity in patients with Crohn's disease.

BACKGROUND: Pancreatitis and exocrine pancreatitic insufficiency have been described as extraintestinal manifestations of inflammatory bowel disease. In this study, we investigated whether the endocrine pancreatic function is also disturbed in patients with inflammatory bowel disease. METHODS: Seventeen patients with Crohn's disease and 13 healthy volunteers participated in the study. We analyzed the plasma insulin response in a 75-g oral glucose tolerance test. Glucose and insulin levels were determined at time 0 (fasting levels) and 30, 60, 90, 120, 180, 240, and 300 min after glucose uptake. Insulin resistance and beta cell function (BCF) were analyzed by calculating respective indices. RESULTS: Fasting and oral glucose-tolerance test glucose levels appeared to be similar in patients with Crohn's disease and in the controls. Impaired fasting glucose, impaired glucose tolerance, and/or overt diabetes mellitus were not observed in the volunteers. Insulin as well as the index for BCF were significantly increased in patients with Crohn's disease. In addition, insulin resistance was shown to be significantly elevated in Crohn's disease. CONCLUSIONS: Patients with Crohn's disease reveal an increased insulin secretion caused by an enhanced BCF, which may be induced by an up-regulated enteropancreatic axis. This hypersecretion may override the insulin resistance given by the chronic inflammatory state.

Risk factors for mortality in severe upper gastrointestinal bleeding.

BACKGROUND AND AIMS: Factors related to mortality after upper gastrointestinal (GI) bleeding may differ in importance in high- and low-risk populations. This retrospective study was undertaken to define risk factors of mortality in patients needing endoscopy for upper gastrointestinal bleeding at a tertiary care centre. PATIENTS/METHODS: Three hundred and sixty-two patients with upper gastrointestinal bleeding were identified from endoscopy charts. Patients' characteristics, bleeding parameters, clinical presentation, pre-existing medication and laboratory data were retrieved from hospital charts and patients who survived and those who died in hospital were compared. RESULTS/FINDINGS: The mean Rockall score was 6.6+/-1.3 with 92.5% of patients belonging to a Rockall high-risk group. In hospital, mortality was 26.5%, with 6.4% of patients dying as a direct consequence of bleeding. Variceal bleeding was associated with a high risk of recurrent bleeding and death. Renal disease, liver disease, coagulopathy and immunosuppression were more frequently found in non-survivors than in survivors. Accordingly, serological tests of renal or liver function and coagulation were more disturbed in non-survivors. On average, heart rate was higher, and blood pressure and haemoglobin levels lower in non-survivors. Heparin, glucocorticoids, and anti-ulcer drugs were more frequently used in patients dying in hospital. By logistic regression analysis, in-patient status at the time of bleeding, renal disease and coagulopathy, as well as glucocorticoid use, were risk factors for hospital mortality. INTERPRETATION/CONCLUSION: In tertiary care, a high mortality rate is observed in upper GI bleeding. Teams involved in treating such patients should be aware of the setting in which treatment is performed and its related risk factors.

Comparison of inpatient and outpatient upper gastrointestinal haemorrhage.

BACKGROUND AND AIMS: Inpatients developing upper gastrointestinal (GI) haemorrhage are at increased risk of death. This study was performed to elucidate differences in inpatients and outpatients. PATIENTS/METHODS: Three hundred and sixty-two patients who needed esophagogastroduodenoscopy for upper GI bleeding were identified from endoscopy charts. Patients' characteristics, bleeding parameters, clinical presentation, pre-existing medication, and laboratory data were compared between patients who were admitted because of upper GI bleeding and patients who developed bleeding while in hospital for other reasons. RESULTS/FINDINGS: Hospital mortality was 39.0% in inpatients vs. 11.1% in outpatients (p<0.01). Death due to bleeding was observed in 9.5% of inpatients vs. 2.5% of outpatients (p<0.01). Whereas peptic ulcer was the most common source of bleeding in both, variceal bleeding was the most common cause of death because of haemorrhage in both. Recurrent bleeding was associated with mortality in outpatients (p<0.001), but not in inpatients (p=0.11). Rates of bleeding recurrence and need for surgery was similar in both groups. Inpatients suffered more often from renal disease, pulmonary disease, diabetes mellitus, coagulopathy, or immunosuppression, and were treated more frequently with acetylsalicylic acid, glucocorticoids and heparin. The frequency of pre-existing disease was higher in inpatients. INTERPRETATION/CONCLUSION: Higher mortality after GI bleeding in inpatients than in outpatients is due to a generally higher prevalence of co-morbidity rather than a single or a few risk factors.

Gallbladder motility in healthy volunteers: effects of age, gender, body mass index, and hair color.

BACKGROUND/AIMS: Ultrasonographic determination of gallbladder motility is sparsely performed in clinical practice as the examination is considered to be time consuming and there is uncertainty about a number of parameters possibly influencing the results. The aims of this study were a) to establish normal values for a simple ultrasonographic test and b) to evaluate the influence of different parameters on gallbladder motility. METHODOLOGY: In 62 systematically age- and sex-matched healthy volunteers, ultrasonographic measurements of gallbladder volume (ellipsoid method, planimetry and sum-of-cylinders method) were performed fasting and 5, 10, 20, 30, 40, 50, 60, 70 and up to 75 min after stimulation with a standardized high-caloric liquid meal. RESULTS: Using the ellipsoid method, gallbladder fasting volume (V0) reached a mean value (+/- SD) of 24.6 +/- 10.0 mL with an ejection fraction of 65.9 +/- 19.1%. Age, gender and hair color did not influence parameters of gallbladder contraction. Body mass index showed a weak correlation with V0 but not with ejection fraction. There was a highly significant correlation between the ellipsoid method and longitudinal planimetry and the sum-of-cylinders method, respectively. CONCLUSIONS: Ultrasonographic measurement of gallbladder motility in healthy volunteers shows a very wide scattering of normal values. In the interpretation of gallbladder emptying, age, gender and body mass index do not have to be considered. Determination of gallbladder motility may be performed by a rather simple approach with oral stimulation and ellipsoid method or longitudinal planimetry as easily applicable ultrasonographic measurements.

Prior bowel resections, perianal disease, and a high initial Crohn's disease activity index are associated with corticosteroid resistance in active Crohn's disease.

OBJECTIVES: Some patients with Crohn's disease (CD) do not respond to corticosteroid therapy. Furthermore, corticosteroids frequently cause side effects. Thus, predictive parameters for treatment refractoriness would be helpful for treatment decisions. METHODS: A total of 300 patients with active CD (i.e., with a Crohn's Disease Activity Index [CDAI] >200) entered the study. Treatment started with 60-100 mg/day prednisolone equivalent, which was then tapered to 10-15 mg/day within 6 wk and maintained at that dose for another 4 wk. After 10 wk of treatment, response to steroids was defined by a CDAI <150, steroid resistance by a CDAI always > or =150 and steroid dependency by a relapse after dose reduction. Of 239 eligible patients, 196 were responders, 26 were steroid resistant, and 17 were steroid dependent. RESULTS: Prior bowel resections, a high initial CDAI, and perianal disease were associated with steroid resistance. Of the steroid resistant patients 53.9% were bowel-resected compared to 20.4% of the responders (relative risk = 3.63; 95% CI = 1.79-7.36). Perianal disease was observed in 42.3% of steroid resistant patients versus 21.9% of responders (relative risk = 2.28; 95% CI = 1.12-4.66) and initial CDAI was 347+/-91 in resistant patients versus 301+/-81 in responders (p < 0.05). Parameters for steroid dependent patients were not significantly different from those of responders. CONCLUSIONS: In this study (thus far the largest study for the evaluation of predictive factors for treatment refractoriness to corticosteroids in CD), only prior bowel resection, perianal disease, and a high initial CDAI were found to be predictive of resistance to steroid treatment.

Screening for osteoporosis in patients with inflammatory bowel disease by using urinary N-telopeptides.

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of osteoporosis. DESIGN AND METHODS: We carried out a prospective study of bone mineral density and biochemical markers of bone metabolism like osteocalcin and urinary N-telopeptides in 72 patients with inflammatory bowel disease and evaluated if one of these markers detects osteoporosis. In addition, bone mineral density and N-telopeptides were analysed retrospectively in a second series of 93 patients with inflammatory bowel disease in order to assess predictive values found in the first patient group in an independent sample. RESULTS: Multiple linear regression showed that N-telopeptides (P < 0.0001) and total white blood cell count (P = 0.006) correlated negatively with the bone mineral density of the lumbar spine and only N-telopeptides (P = 0.005) correlated negatively with the bone mineral density of the femoral neck. Using receiver operator characteristic curves N-telopeptide concentrations of > 40 (30) nmol N-telopeptides/mmol creatinine were chosen as best cut-off values to exclude osteoporosis at the lumbar spine (femoral neck). Using these cut-off values a negative predictive value of 100% (100%) and a positive predictive value of 37.5% (27.9%) were found in the first group, and a negative predictive value of 95.2% (96%) and a positive predictive value of 15.6% (23.3%) in the second, independent group of patients. CONCLUSION: Our data suggest that N-telopeptide levels could be used as a tool for the screening of osteoporosis and for selecting those inflammatory bowel disease patients where bone mineral density measurement is indicated.