Mo1167 Hypercoagulability and Autoimmune Risk Assessment is Important in Diabetic Gastroparesis

Abstract

Introduction: There are reports of close contacts between nerve varicosities, smooth muscle cells, interstitial cells of Cajal (ICC) and fibroblast-like cells (PDGFR-α+ cells) in the gastrointestinal tract. Experimental studies of diabetes in animals suggest that the disease process can affect enteric nerves, extrinsic nerves, ICC and smooth muscle. By contrast, human data are sparse and generally inadequate for the validation of data obtained from experimental models. The aim of this study was to investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus (DM). Methods: Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. To investigate the pathological changes of stomach, H&E stain, Masson Trichrome stain and immunohistochemical examination were done on the sections. Antibodies against protein gene product (PGP) 9.5, neuronal NO synthase (nNOS), vasoactive intestinal peptide (VIP), neurokinin 1, c-Kit, and PDGFR-α were used. Immunofluorescent stain and evaluation with confocal microscopy were also done. Results: Tissues were collected from 26 controls, 21 short duration DM patients and 14 long duration DM patients (39 males/22 females, mean age 61.2 ± 9.6 y). In clinical characteristics, there were no significant differences of age and proportions of gender and upper gastrointestinal symptoms between DM group and control group. Mean BMI in the DM group was higher than that in the control group (p<0.05). The proportions of moderate to severe intercellular fibrosis in muscle layer were significantly higher in DM group than these in control group (p<0.01). On immunohistochemical staining, c-Kit and PDGFR-α positive immunoreactivity were significantly decreased in DM group compared with control group (p<0.05). There were no statistically significant differences in the PGP 9.5, nNOS, VIP and neurokinin 1 expression between DM group and control group. On immunofluorescent staining and confocal microscopic examinations, network of ICC and fibroblast-like cells in the muscle layer were greatly decreased in the DM group compared with control group. Conclusions: Our study suggests that on full-thickness gastric specimens, increased intercellular fibrosis and loss of ICC and fibroblast-like cells are found in the smooth muscle of patients with DM. These cellular abnormalities likely reduce the functional capacity of the gastrointestinal motor apparatus and may contribute to changes of gastrointestinal motility in patients with DM.