Abnormal intestinal permeability to sugars in diabetes mellitus (original) (raw)
Related papers
Digestive and Liver Disease, 2004
Background. Increased intestinal permeability was described in several intestinal auto-immune conditions. There are very few and contradictory reports about type I diabetes mellitus, an auto-immune condition sometimes associated with celiac disease.Aims. To investigate intestinal permeability in type I diabetes mellitus patients with no concomitant celiac disease, with a comparison to ultra-structural aspects of duodenal mucosa.Patients. 46 insulin dependent diabetes mellitus, non-celiac, patients (18 females and 28 males, mean age 15.8±5.3 [S.D.] years) were enrolled. The mean duration of the disease was 5.7 years.Methods. The morphological aspect of the small bowel mucosa, at standard light microscopy and electron transmission microscopy, along with intestinal permeability (by lactulose/mannitol test) were studied. Lactulose and mannitol urinary excretion were determined by means of high performance anion exchange chromatography–pulsed amperometric detection.Results. The lactulose/mannitol ratio was 0.038[0.005−0.176] (median and range) in 46 patients compared to 0.014[0.004−0.027] in 23 controls: insulin dependent diabetes mellitus group values being significantly higher than those of the controls (P<0.0001, Mann–Whitney test). Eight insulin dependent diabetes mellitus patients underwent endoscopy and biopsies were analysed by means of light microscopy and transmission electron microscopy. At the light microscopy level, none of the biopsy samples showed any sign of atrophy nor inflammation, whereas transmission electron microscopy analysis showed remarkable ultra-structural changes in six out of the eight patients. Four parameters were evaluated: height and thickness of microvilli, space between microvilli and thickness of tight junctions.Conclusions. This alteration of intestinal barrier function in non-celiac type I diabetes mellitus, frequently associated with mucosal ultra-structural alterations, could suggest that a loss of intestinal barrier function can be a pathogenetic factor in a subset of insulin dependent diabetes mellitus patients.
Increased intestinal permeability precedes clinical onset of type 1 diabetes
Diabetologia, 2006
Aims/hypothesis Recent observations have shown subclinical intestinal abnormalities in human type 1 diabetes. Whether these are related to the pathogenetic process or secondary to the diabetes remains to be clarified. The aim of this study was to investigate this issue by examining intestinal permeability to sugars in subjects at different stages of type 1 diabetes: preclinical, new-onset and long-term established disease. Methods Eighty-one subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose-mannitol test, consisting of oral administration of the two sugars and measurement of their urinary excretion. Results All groups of subjects with islet autoimmunity showed an increase in intestinal permeability (p ≤ 0.009 vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but a similar permeability to the monosaccharide mannitol (NS vs controls), indicative of an integral surface mucosa; consequently there was an increase in the lactulose:mannitol excretion ratio (p ≤ 0.025 vs controls). Conclusions/interpretation These findings indicate the presence of a subclinical enteropathy associated with type 1 diabetes that is already detectable before clinical onset of the disease, and suggest that the small intestine is an organ participating in the pathogenetic process of type 1 diabetes.
Pattern of small intestinal mucosal changes in patients with type 1 diabetes mellitus
Background: The coexistence of type 1 diabetes mellitus (DM) and Celiac disease (CD) is well recognized with a prevalence of CD in type 1 DM reported to be between 0% and 10.4%. The aim of this study was to find the pattern of small intestinal mucosal changes in patients with type 1 DM. Methods: a cross-sectional study done in Al-Faiha hospital in Basrah , Iraq , on patients with type 1 DM. Duodenoscopy was done , and at least four biopsies were taken from the second part of the duodenum. Results: Four patients had normal biopsy, 16 patients had duodenitis, and 10 patients had Marsh type I. Marsh type IIIA were seen in 4 patients, Marsh IIIB were seen in two patients, and Marsh IIIC in 4 patients. Marsh IIIB and C histology were regarded compatible with CD, so the incidence of CD was 15%. Conclusion: all patients with type 1 DM should be screened for CD.Duodenal biopsy is a relevant tool for screening CD in patients with type I DM.
Gluten challenge in borderline gluten-sensitive enteropathy
The American Journal of Gastroenterology, 2001
In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive.
Gut, 1993
To study changes in rectal mucosa that might be attributable to the effects of gluten, rectal biopsy specimens from untreated and treated gluten sensitised subjects were analysed morphometrically and by immunohistochemical techniques and were compared with a series of disease control mucosae. Although morphometry showed increased populations of plasma cells, lymphocytes, and mast cells in the mucosae of untreated patients, which were reduced (except for mast cells) by dietary gluten restriction, immunohistochemical techniques were far more sensitive in defining these changes. There were highly significant increases in CD3+ and yb' lymphocytes within both the lamina propria and the epithelium while neutrophils (CD15+ cells) were not at all prominent. Activated (CD25+) lymphocytes expressing interleukin (IL)-2 receptors were increased in lamina propria, usually subjacent to basal lamina, although a few IL-2R+ intraepithelial lymphocytes were found: other IL-2R+ cells were deemed to be macrophages (CD68+). These results clearly indicate that in untreated, gluten sensitised subjects the rectal mucosa shows a lymphoplasmacytoid reaction that is responsive to gluten restriction. The absence of neutrophilia suggests that this lesion is not a conventional inflammatory type proctitis, but rather one presumed to be induced by gluten antigen(s) present in the faecal streamthat is, a cell mediated form of response.
Evaluation of a triple sugar test of colonic permeability in humans
Acta Physiologica Scandinavica, 2004
Conventional dual sugar tests of intestinal permeability assess only the stomach and small intestine. A novel triple sugar method of assessing colonic permeability has recently been described in animals. This utilizes the nonfermented sweetener sucralose, in addition to conventional sugars. It has been postulated that this test enables the simultaneous assessment of smallintestinal and colonic barrier function in humans. The aim of this study was to evaluate the triple sugar test using healthy volunteers and ileostomists. Methods: Twenty-one healthy volunteers and 18 ileostomists underwent the triple sugar test. After an overnight fast, subjects drank a solution containing lactulose (5 g), rhamnose (1 g) and sucralose (5 g). Urine was collected for 0-5 h and 5-19 h. Urinary sugars were quantified using HPLC, and 5 and 24-h excretion calculated. Nineteen control subjects and 16 ileostomists also underwent a 51 Cr-EDTA permeability test. Permeability data were presented as medians (IQR), and differences between groups analysed with Mann-Whitney U-tests. Results: Lactulose excretion and the 5-h lactulose/rhamnose (L/R) ratio were similar in controls and ileostomists [L/R ratio 0.024 (0.022-0.034) vs. 0.025 (0.022-0.035), P ¼ 0.955]. Twenty-four hours excretion of sucralose was significantly higher in control subjects compared with ileostomists [1.41% (1.17-1.68) vs. 0.96% (0.64-1.2), P ¼ 0.003]. The same pattern was seen with 51 Cr-EDTA [2.73% (2.06-3.76) vs. 2.06% (1.55-2.71), P ¼ 0.037] and with lactulose [0.52% (0.42-0.60) vs. 0.25% (0.16-0.35), P ¼ 0.002]. Conclusions: Both sucralose and 51 Cr-EDTA underwent significant colonic absorption. A significant amount of lactulose also appeared to be absorbed in the colon. This unexpected finding requires further study.
The sugar absorption test: clinico-pathophysiological considerations
1995
After studying intestinal permeability in immunologic disorders, we studied intestinal permeability in a nonimmunologic disorder, exocrine pancreatic insufficiency.(chapter 5) In childhood, exocrine pancreatic insufficiency occurs mainly in patients with cystic fibrosis. We measured intestinal permeability in cystic fibrosis- and non cystic fibrosis patients with pancreatic insufficiency and found that intestinal permeability was increased in both groups. In cystic fibrosis patients, we found that intestinal permeability did not change by increasing pancreatic enzymes supplementation y 30-50o/o for 2 weeks, nor by decreasing the osmolarity of the test solution of the SAT by 75o/oW. e conclude that an increased intestinal permeability in cystic fibrosisis probably a consequence of pancreatic insufficienry, and is not related to the dose of pancreatic enzyme supplementation nor the osmolarity of the test solution. The increase is due to an increased permeability for lactulose which mi...
TYPE 1 DIABETES MELLITUS AS AN EXTRA INTESTINAL MANIFESTATION OF CELIAC DISEASE: THE IMPORTANCE OF SCREENING AND EARLY TREATMENT (Atena Editora), 2023
Introduction: Celiac disease (CD) is an autoimmune disease that has a specific serological and histological profile that occurs after gluten ingestion by genetically predisposed patients. The disease has a wide spectrum of symptoms and multifactorial causes. In addition, the disease is characterized by being difficult to diagnose, in part due to the wide range of clinical manifestations that can misdirect and prevent diagnosis. Type 1 Diabetes Mellitus (DM1) is a chronic autoimmune disease that leads to complete or partial destruction of pancreatic beta cells, thus resulting in a progressive inability to produce insulin. DM1 causes several lesions in different organs, due to micro and macrovascular alterations, which generate dysfunctions and insufficiencies in the body. It is known that there is an intimate relationship between these two pathologies, the prevalence of CD among patients with DM1 has been estimated at approximately 4.0%. This association between the two pathologies occurs due to the presence of the human histocompatibility antigen (HLA) DQ, encoded by the DQ2 and DQ8 genes on chromosome 6, which suggests a genetic cause for the simultaneous occurrence of the two diseases, since such genes are shared by DM1, CD and other autoimmune diseases. Goal: To carry out an integrative literature review to seek to understand the relationship between celiac disease and type 1 diabetes, as well as the pathophysiology and immunopathogenesis involved in the association between these two pathologies. Method: PubMed, SciELO, and LILACS databases were methodically searched from 2000 to 2021 to identify all studies that evaluated the relationship between celiac disease and type 1 diabetes. Results: According to the studies analyzed, celiac disease was associated with a statistically significant increase in the risk of subsequent type 1 diabetes before age 20. In addition, prevalence of biopsy-confirmed celiac disease was also found in about 6% of the population with T1DM. In this study, the prevalence was lower in adults with type 1 diabetes (2.7%) and in mixed populations with children and adults with type 1 diabetes (4.7%) than in children (6.2%) with type 1 diabetes. 1. The correlation between the prevalence of patients with Type I Diabetes Mellitus and Celiac Disease is notorious, and CD often manifests itself asymptomatically, which may worsen the clinical picture regarding DM1. Diagnosis and adequate treatment of CD are essential for the reduction of possible complications and risks resulting from diabetes to be possible, promoting an improvement in the quality of life of patients with both comorbidities. Celiac Disease may be responsible for accelerating the worsening of Type I Diabetes Mellitus, with the onset of chronic complications of DM1 prematurely. An example of a complication is Diabetic Nephropathy (DN), which appears earlier in patients with CD at the same time, since the role of the disease in the development of chronic hyperglycemia is suspected, which, in addition to culminating in a thickening of the glomerular basement membranes, in the kidneys, also has other repercussions in different body systems, as in the case of Diabetic Nephropathy. In addition, the state of hyperglycemia generated in the body is a triggering factor for Peripheral Neuropathy, a condition characterized by a change in the conduction of nerve impulses, due to the excessive entry of glucose into the cells of the neuronal and endothelial tissues. The association between both diseases is also responsible for causing a greater cardiovascular risk for the patient, since it was identified that individuals with both diseases have lower levels of HDL-cholesterol, associated with possible more severe conditions of atherosclerosis, in due to a greater thickening of the intima-media layer . Conclusion: In many cases, celiac disease symptoms go undiagnosed, as most individuals assume they are just symptoms of diabetes. Therefore, for a better control of type 1 diabetes mellitus to be carried out, it is imperative that the underlying cause of any symptom experienced by the patient be discovered. People who have DM1 and CD concomitantly have difficult diabetes control. The complexity of treating T1DM in patients with celiac disease is due to the fact that gluten in food causes inflammation in the intestine, which changes the way food is absorbed. This causes blood sugar fluctuations to be carried out more frequently and also with greater intensity. Thus, for individuals who have both autoimmune diseases, it is critical that a strict diet be followed to reduce the risk of diabetes and untreated celiac disease.
Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat
Diabetologia, 2005
Aims/hypothesis: A deranged mucosal immune response and dietary factors may play an important role in the pathogenesis of type 1 diabetes. The aims of our work were to look for the presence of small intestinal enteropathy in non-obese diabetic (NOD) mice in relation to the presence of wheat proteins in the diet, and to assess their role in the risk of developing diabetes. Methods: Female NOD mice were fed a standard or gluten-free diet or a gluten-free diet with the addition of wheat proteins (MGFD). Small intestine architecture, intraepithelial CD3 + infiltration, epithelial expression of H2-IA, mRNA for IFN-gamma and IL-4 were assessed. Results: NOD mice fed a standard diet showed reduced villous height, increased intraepithelial infiltration by CD3 + cells and enhanced expression of H2-IA and IFN-gamma mRNA when compared with mice on the gluten-free diet. The cumulative diabetes incidence at 43 weeks of age was 65% in the latter and 97% in the former (p<0.01). Mice on MGFD also showed increased epithelial infiltration and a higher incidence of diabetes. Conclusions/ interpretation: Mice fed a wheat-containing diet showed a higher incidence of diabetes, signs of small intestinal enteropathy and higher mucosal levels of proinflammatory cytokines.