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Sugar metabolism, GERD and Barrett's esophagus: role of insulin.

27.10.2011 by Reflux Medical

Reflux Medical
Endoscopically normal appearing squamocolumnar junction in the distal esophagus.

Persons with GERD symptoms ± Barrett‘s esophagus have increased insulin and insulin like growth factor-1 levels: evidence for a contribution of the sugar metabolism in GERD and Barrett‘s esophagus (i.e. YOU are what you EAT, healthy or sick).

Association of insulin and insulin-like growth factors with Barrett‘s esophagus.

Greer KB, Thompson CL, Brenner L, et al.

Gut 2011, ahead print.

Insulin, a key regulator of the sugar metabolism, promotes tumor growth via stimulation of the growth factor-1 (IGF-1). In addition insulin down-regulates the IGF-binding proteins (IGFBP-1 and 2) and thus increases the bioavailability of IGF-1. This in turn mediates receptor mediated responses including tumor growth.

Barrett‘s esophagus is columnar lined esophagus with intestinal metaplasia (CLE+IM). Due to gastroesophageal Reflux the normal Squamous epithelium is damaged and replaced by columnar Epithelium containing goblet cells, the histopathological hallmark of Barrett‘s esophagus. Therefore Barrett‘s esophagus is associated with the symptoms of Gastroesophageal reflux disease ( GERD). Via Dysplasia the nondysplastic Barrett‘s esophagus may progress to Esophageal adenocarcinoma (0.5% annual risk).

The present hospital-based-case-control-study compared the levels of serum insulin (after 6-8 hrs. fast), IGF-1 and the IGFBP-1 & 2, and insulin resistance in:
persons with GERD symptoms + Barrett‘s esophagus without Dysplasia,
individuals with GERD symptoms without Barrett‘s esophagus
individuals without GERD symptoms, absence of endoscopic evidence of Barrett‘s esophagus and normal colonoscopy (=screening controls).

The authors defined Barrett‘s as:
endoscopically visible columnar lined esophagus ( CLEV)
with intestinal metaplasia within biopsies obtained from the squamocolumnar junction.

Biopsies were only obtained in persons with endoscopically visible columnar lined esophagus. Upper GI Endoscopy information was not available for all of the screening controls, and was neglected, because it was assumed that the presence of Barrett‘s (= CLEV + intestinal metaplasia) in this group equals almost zero.

Mean serum levels of insulin and IGF-1were comparably increased in persons with GERD symptoms ± Barrett‘s vs. the colonoscopy group (no GERD symptoms, no endoscopcially visible columnar lined esophagus; p<0.05).
Mean serum levels of IGFBP-1 & 2 were significantly increased vs. the other groups.
Persons with Barrett‘s esophagus had an increased insulin resistance, when compared to the screening colonoscopy group (OR 2.23). This difference vanished when Barrett‘s were compared to matched colonoscopy controls.

Increased serum levels of insulin, IGF-1 and decreased levels of the insulin growth factor binding proteins (=i.e. increased bioavailability of IGF-1) may contribute to the formation of Barrett‘s esophagus and indicate, that metabolism is somehow connected to GERD and Barrett‘s esophagus.

iGERD Comment:
Conceptually the study design is touching and fascinating. However the study harbors major drawbacks, which have been missed by the Editors of GUT. Accurately read the data indicate that persons with GERD symptoms and endoscopically visible columnar lined esophagus ( CLEV) ± intestinal metaplasia have increased serum insulin levels, when compared to those without GERD symptoms. The correct interpretation of the data indicates, that insulin might have something to do with the mediation of the GERD symptoms, i.e. that persons with GERD symptoms have increased insulin levels and IGF-1 levels, when compared to those without GERD symptoms. Symptoms are mediated via nerves, this indicates that nerve function is somehow affected in persons with increased serum insulin levels. Remains to be questioned the clinical relevance?
Persons perceiving GERD symptoms seem to have a massive problem with their sugar, glycogen, insulin metabolism, as indicated by their increased insulin resistance. Most probably both GERD and Barrett‘s esophagus (and tumor development) suffer from a stressed sugar metabolism. Therefore those conditions may at least be partially reversed by a diet free of concentrated carbohydrates? Diet against GERD, Barrett‘s esophagus and for cancer prevention. Give it a try and eliminate concentrated sugars out of your diet. See respective informations about nutrition & body balance within .
A other drawback is the fact that the authors assumed that a normal appearing endoscopically visible esophagogastric junction, i.e. absence of endoscopically visible columnar lined esophagus, EXCLUDES Barrett‘s esophagus. Ringhofer et al. (1) have recently demonstrated indifferent frequency of Barrett‘s esophagus in GERD patients with normal and abnormal endoscopic esophagogastric junction (p>0.05).
Finally, the authors assumed the absence of Barrett‘s esophagus in persons without GERD symptoms. We have assessed, that the frequency of Barrett‘s esophagus in those with and without Barrett‘s esophagus is statistically insignificant different (p>0.05; unpublished data). The consequence: we can not exclude that the insulin-study missed a significant number of Barrett‘s within the controls. If this was so, the value of the paper decreases to ZERO. Future investigations should address this issue and prove that we are wrong.

1. Ringhofer et al. Wien Klin Wochenschrift 2008; 120/11-12: 350-59.

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