Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients

Dig Liver Dis. 2004 Jan;36(1):35-45. doi: 10.1016/j.dld.2003.09.016.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Endoscopy, Gastrointestinal
  • Female
  • Gastrointestinal Agents / metabolism
  • Humans
  • Intestinal Absorption / physiology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure*
  • Lactulose / metabolism
  • Male
  • Permeability


  • Gastrointestinal Agents
  • Lactulose