OBJECTIVE: Approximately 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients. RESEARCH DESIGN AND METHODS: Gastric biopsies from 88 consecutively recruited type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 +/- 13 years) were evaluated using the updated Sydney system. Immunostaining was done for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence, H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath test, and histology. Pentagastrin tests were performed in 42 subjects. RESULTS: Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P < 0.0001). PCA positivity (beta = 1.44; P = 0.04) and hypergastrinemia (beta = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015), pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P = 0.0002) were more frequent in AG+ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG+ patients, including 1 with linitis plastica. CONCLUSIONS: PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.