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 ϩ and 62 PCA Ϫ , aged 45 Ϯ 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 -PCAϩ patients had higher gastrin (P Ͻ 0.0001) and CgA levels (P ϭ 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P Ͻ 0.0001) and ECL cell hyper/dysplasia (OR ϭ 23, P ϭ 0.005) than PCA Ϫ subjects. ECL cell hyper/dysplasia was present in seven PCA ϩ patients who showed higher CgA levels (P Ͻ 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r ϭ 0.50, P Ͻ 0.0001), PCA titer (r ϭ 0.42, P ϭ 0.001), and 5-HIAA levels (r ϭ 0.38, P ϭ 0.012). Logistic regression identified the CgA level ( ϭ 0.01, P ϭ 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 ϭ 0.59, P Ͻ 0.0001) and gastrin level (r ϭ 0.67, P ϭ 0.02). One PCA ϩ patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor.
CONCLUSIONS -PCAϩ 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.