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Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease.

BACKGROUND: Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin-resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance. AIM: To measure body composition, whole body glucose uptake and oxidation in Crohn's disease and ulcerative colitis patients with inactive disease. METHODS: All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn's disease (five males, aged 31.1 +/- 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 +/- 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group. RESULTS: Crohn's disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (micromol/kg/min) was found between groups (respectively 42.5 +/- 6.78 in Crohn's disease, 40.2 +/- 8.00 in ulcerative colitis and 41.4 +/- 10.8 in control subjects). Glucose storage and oxidation did not differ between groups. CONCLUSION: Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat-free mass preservation and low blood and tissue cytokine concentration.

Adolescent↗

Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease.

BACKGROUND: Despite strong evidence implicating immune dysfunction and genetic predisposition in the pathogenesis of the chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis, the importance of the genes of the major histocompatibility complex remains uncertain. We have investigated the contribution of HLA DRB1 and DQB genes by the strategies of non-parametric linkage analysis (affected sibling pair method) as well as association study. The relation between genotype and phenotype was examined in detail. METHODS: For linkage analysis 74 families in whom two or more siblings had inflammatory bowel disease were studied. A total of 83 affected sibling pairs were involved: in 42 pairs both siblings had Crohn's disease; in 29 both had ulcerative colitis; in 12 one sibling had Crohn's disease, the other ulcerative colitis. For the association study there were 175 patients with ulcerative colitis, 173 with Crohn's disease, and 472 controls. Details of sex, age of onset, disease extent, and family history were analysed. 24 patients with ulcerative colitis and 92 with Crohn's disease required surgery for refractory disease. HLA DRB1 and DQB1 gene-typing was performed by polymerase chain reaction with sequence-specific primers. FINDINGS: In ulcerative colitis, the sharing of alleles among affected sibling pairs provided evidence for linkage with DRB1 locus (p = 0.017, chi2 = 5.32). Of 29 affected sibling pairs studied, only one pair shared no DRB1 DQB haplotypes. 15 shared two DRB DQB haplotypes. In contrast, no linkage was noted for Crohn's disease (42 sibling pairs; p = 0.30, chi2 = 0.16) or for inflammatory bowel disease overall (83 sibling pairs, p = 0.16, chi2 = 2.28). In the association study the rare DRB1*103 (8.3% vs 3.2% in controls) and DRB1*12 (8.6% vs 2.1% in controls) alleles were associated with ulcerative colitis (p = 0.0074, chi2 = 7.22, odds ratio OR = 2.9 [95% CI 1.3-6.4] and p = 0.0056, chi2 = 12.63, OR = 4.33 [1.8-11.0] respectively). No association with alleles representing DR2 (p = 0.55, chi2 = 0.34) was noted. No overall association was seen in Crohn's disease. In ulcerative colitis, the frequency of DRB1*0301 DQB*0201 (DR3 DQ2) was reduced in females (9.8% vs 26.3% in controls, p = 0.037, chi2 = 8.39 OR = 0.34 [0.15-0.71]), particularly in those with distal disease (2.3%, p = 0.001 vs controls, chi2 = 11.35, OR = 0.07 [0.00-0.39]). In both males and females, the DR3 DQ2 haplotype was predictive of extensive ulcerative colitis (32.9% vs 10.7% in distal disease, p < 0.01, chi2 = 10.94, OR 4.09 [1.70-10.6]) but not of need for surgery (p = 0.93, chi2 = 0.01). INTERPRETATION: These data provide strong evidence for genetic heterogeneity in inflammatory bowel disease. Genes of the major histocompatibility complex are implicated as important inherited determinants of susceptibility to ulcerative colitis and may also influence the pattern of disease. In Crohn's disease, important susceptibility genes are likely to exist outside the HLA region.

Adult↗

[Imaging diagnosis of inflammatory bowel disease].

The term "chronic inflammatory bowel disease" represents a spectrum of diseases out of which ulcerous colitis and Crohn's disease are the far most common. Large bowel enemas have lost their relevance compared to colonoscopy over the past years and small bowel enteroclysis has also been widely replaced by CT- and especially MR-enteroclysis meanwhile. The diagnostic value of computed tomography and MR-tomography in chronic inflammatory bowel disease is based on the excellent visualization and documentation of extent and severity of bowel wall inflammation, estimation of inflammatory activity of the disease and of detection of potential extraintestinal complications and/or additional diagnoses by these two methods. Nevertheless, conventional radiological techniques as well as sonography may still be valuable under certain conditions. Furthermore, nowadays imaging of chronic inflammatory bowel diseases includes also White Blood Cell scintigraphy as well as Positrone Emission Tomography which provide informations about extent and especially activity of the disease. The presented article provides an overview of the possibilities and limitations of the available imaging modalities in inflammatory bowel diseases and helps the reader to decide under what conditions which one of the available examinations should be regarded as the most appropriate and promising one.

Colitis, Ulcerative↗

Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors.

Adolescent↗

Anti-neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in Chinese.

Inflammatory bowel diseases are uncommon in the Chinese, but the incidence is rising. Their differentiation from infective colitis is often not clear-cut and diagnosing inflammatory bowel diseases can be difficult in Asia. We have studied Chinese patients with ulcerative colitis (N = 19) and Crohn's disease (N = 12) for anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA). Patients with enteric fever (N = 29) and irritable bowel syndrome (N = 24) were recruited as controls. Seventy-three percent of ulcerative colitis patients exhibited either p-ANCA (31%) or c-ANCA (42%) by IIF. Twenty-five percent of Crohn's disease patients were found to be p-ANCA positive. However, these ANCA were nonreactive to anti-alpha granule, antiproteinase 3, antimyeloperoxidase, or antilactoferrin. All positive patients had extensive colitis. Sera collected from patients suffering from enteric fever and irritable bowel syndrome were negative for ANCA by IIF and ELISA. We concluded that the detection of ANCA is helpful in diagnosing inflammatory bowel diseases. Further attempts to characterize these autoantibodies are needed.

Adult↗

Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease.

BACKGROUND: Intestinal and peripheral blood mononuclear cell interleukin 6 (IL-6) production in inflammatory bowel disease might present an increased quantity of IL-6 into the systemic circulation. The aim of the present study was to examine the relationship of circulatory IL-6 to the clinical and laboratory expression of inflammatory bowel disease in children. METHODS: Sera were obtained from 26 children with ulcerative colitis, 49 with Crohn's disease, and 29 control patients. Serum functional IL-6 was measured by a bioassay and antigenic IL-6 by enzyme linked immunosorbent assay. RESULTS: Functional and antigenic serum IL-6 levels were higher in Crohn's disease than in ulcerative colitis or controls (P < 0.0001) and higher in ulcerative colitis than controls (P < 0.04). In Crohn's disease affecting the colon, functional and antigenic serum IL-6 levels were greater than in disease limited to the small bowel (P < 0.002). Increasing disease severity was reflected by increasing antigenic but not functional IL-6 levels in both Crohn's disease (P < 0.001) and ulcerative colitis (P < 0.02). Serum antigenic IL-6 levels were related to acute phase reactants in both diseases (P < 0.001) whereas functional levels were not. CONCLUSIONS: Our results underscore the importance of using both functional and antigenic methodologies in examining the relationship of circulating cytokines to the clinical manifestations of inflammatory bowel disease.

Acute-Phase Proteins↗

Resting and total energy expenditure in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease often present with weight loss. Among possible causes, an elevated energy expenditure has frequently been suggested but is the least documented. In this study resting metabolic rate (RMR) and total daily energy expenditure (TDEE) were measured in 15 outpatients with inflammatory bowel diseases and in eight healthy control subjects. Measured RMR as a percentage of that predicted from fat-free mass was not significantly different for control subjects (102 +/- 9.8%, mean +/- SD) and patients (100 +/- 13.3%). TDEE, expressed as a multiple of RMR, was 1.70 +/- 0.31 for control subjects and 1.78 +/- 0.24 for patients. When patients were subgrouped as greater than or equal to 90% or less than 90% desirable body weight, a mean increase over RMR predicted from fat-free mass was seen in the underweight patients (106 +/- 9.3%) but not in normal-weight patients (99.0 +/- 15.6%). Mean TDEE/RMR values for the patient subgroups were 1.70 +/- 0.30 and 1.88 +/- 0.08, respectively. We conclude that stable outpatients with inflammatory bowel disease have only a minimal increase in energy needs.

Adult↗

Hepatobiliary disease in inflammatory bowel disease.

Many hepatobiliary diseases are seen in IBD. PSC is the most common, occurring in 7.5% of patients with UC. The cause of PSC is not well understood, but PSC seems to be associated with genetic susceptibility, sharing some immunologic abnormalities with UC. A characteristic cholangiogram in a patient with abnormal liver function tests usually establishes the diagnosis. Liver biopsy is not essential but can help make the diagnosis of small duct PSC in patients with a normal cholangiogram. There are no medications that treat PSC effectively. Endoscopic dilation of dominant strictures reduces the frequency of cholangitis and may improve survival. OLT remains the only proven treatment of advanced PSC. Cholangiocarcinoma is a feared complication of PSC that is difficult to diagnose. Cholelithiasis, PBC, portal vein thrombosis, and hepatic abscess are hepatobiliary disorders that occur less frequently in IBD patients.

Biliary Tract Diseases↗

Large airway disease associated with inflammatory bowel disease.

Lung disease is a rare complication of inflammatory bowel disease (IBD). Herein is a series of seven IBD patients who developed new, persistent and unexplained symptoms of respiratory disease, particularly chronic productive cough. Using a CT scan of the chest, a diagnosis of bronchiectasis was made in five patients, while the diagnosis of chronic bronchitis was made in two patients. Factors, other than IBD, that could account for pulmonary disease in these patients were absent. Several important clinical patterns for IBD-associated large airway disease were uncovered and are reviewed in light of earlier case reports in the medical literature. A discussion regarding the possible pathogenesis of IBD-associated airway disease follows.

Adult↗

Surgery for inflammatory bowel disease in Singapore.

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.

Adult↗

Inflammatory bowel disease in children.

Inflammatory bowel disease in children and adults remains the most challenging problem in gastroenterology. There is an increasing body of immunologic and genetic evidence to suggest that Crohn's disease and ulcerative colitis are different diseases, but that once inflammation begins, many common secondary pathways of inflammation are initiated. The major recent conceptual advance is the observation that mice in whom different immunoregulatory pathways are disrupted develop an inflammatory bowel disease. In the case of interleukin-2 knockout mice, the lesion restricted to the colon, is virtually identical to ulcerative colitis in humans, and is initiated by the normal bacterial flora. Yet these mice possess anticolon antibodies, long-considered to be of pathologic significance in ulcerative colitis. These animal models will allow detailed longitudinal studies to be done, and less reliance will need to be placed on cross-sectional studies of chronically inflamed gut from patients.

Age Factors↗

Fecal lysozyme in assessment of disease activity in inflammatory bowel disease.

This study was undertaken to determine whether measurement of fecal lysozyme is helpful in determining disease activity in inflammatory bowel disease. In 112 patients with Crohn's disease, 46 patients with ulcerative colitis, and 40 controls, fecal lysozyme concentration was measured. Results were correlated with CDAI and AI in Crohn's disease and with Truelove and Witts' grading in ulcerative colitis. Fecal lysozyme concentration (mean +/- SEM) was significantly (P < 0.001) higher in Crohn's disease (75 +/- 14 microg/g) and ulcerative colitis (238 +/- 33 microg/g) than in controls (6 +/- 1 microg/g). There was only a weak correlation between fecal lysozyme concentration and CDAI (r = 0.32; P = 0.001) and AI (r = 0.38; P < 0.0005) in patients with Crohn's disease and with Truelove and Witts' grading (r = 0.47; P = 0.001) in ulcerative colitis. When CDAI > or = 150 or AI > or = 100 were used as the standard for active disease, fecal lysozyme concentration was elevated in 78% of patients with active colonic Crohn's disease. In ulcerative colitis fecal lysozyme concentration was increased in active disease (95% in grade II and 94% in grade III) as compared 33% in grade I. Measurement of fecal lysozyme is of little help in diagnosing and determining disease activity of inflammatory bowel disease as whole, but it may be of help for diagnosis and assessment of activity of colonic IBD.

Adult↗

Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease.

The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.

Chromosomes, Human, Pair 1↗

Inflammatory bowel disease and the eye.

Inflammatory bowel disease includes Crohn's disease and ulcerative colitis, and is characterized by chronic inflammation of the intestines. The advances in understanding of the inflammatory process have resulted in improved treatment of inflammatory bowel disease. The systemic complications of inflammatory bowel disease involve many organs, eyes included. The ophthalmic complications are usually of inflammatory origin. Some of these complications, like scleritis, may reflect overall disease activity. Treatment of intestinal inflammation-either medical or surgical-usually helps resolution of ophthalmic complications. This review describes recent developments in the diagnosis and management of the inflammatory bowel disease and its ophthalmic complications.

Colitis, Ulcerative↗