Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes.

Abstract

OBJECTIVE:

Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia.

RESEARCH DESIGN AND METHODS:

Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies.

RESULTS:

PCA(+) patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(-) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor.

CONCLUSIONS:

PCA(+) patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.

• Authors: Christophe E M De Block, Gert Colpin, Kristof Thielemans, Willy Coopmans, Johannes J P M Bogers, Paul A Pelckmans, Eric A E Van Marck, Viviane Van Hoof, Manou Martin, Ivo H De Leeuw, Roger Bouillon, Luc F Van Gaal
• Journal: Diabetes care (Diabetes Care) Vol. 27 Issue 6 Pg. 1387-93 (Jun 2004) ISSN: 0149-5992 [Print] United States
• PMID: 15161793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Biomarkers, Tumor
• Chromogranin A
• Chromogranins
• Hydroxyindoleacetic Acid
• Phosphopyruvate Hydratase

Topics

• Autoantibodies (blood)
• Biomarkers, Tumor (blood)
• Chromogranin A
• Chromogranins (blood)
• Diabetes Mellitus, Type 1 (blood, immunology, pathology)
• Enterochromaffin Cells (pathology, physiology)
• Female
• Helicobacter Infections (complications, epidemiology)
• Helicobacter pylori (isolation & purification)
• Humans
• Hydroxyindoleacetic Acid (blood)
• Hyperplasia
• Male
• Middle Aged
• Neuroendocrine Tumors (blood)
• Phosphopyruvate Hydratase (blood)