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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 (β = 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.

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 (β = 1.44; P = 0.04) and hypergastrinemia (β = 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.

OBJECTIVE—A worldwide increase in the incidence of childhood type 1 diabetes has been observed. Because in various countries the majority of new type 1 diabetic patients are diagnosed in adulthood, we investigated whether the rising incidence of this disorder in children reflects a global increase in the incidence of diabetes or a shift toward earlier clinical presentation. RESEARCH DESIGN AND METHODS—The incidence of type 1 diabetes presenting before age 40 years was prospectively measured in the Antwerp district over a 12-year period (1989–2000). The completeness of ascertainment was evaluated by the capture-recapture method. Trends in incidence during the study period were analyzed by Poisson regression. RESULTS—The incidence of type 1 diabetes diagnosed before age 40 years remained constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per year. The incidence was similar in both sexes under age 15 years, but a marked male excess was noted for adult-onset disease, in particular after age 20 years, resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter (P = 0.001). During the 12-year observation period, there was a significant tendency toward increasing incidence under age 15 years at the expense of a decreasing incidence between ages 15 and 40 years (P = 0.025). The annual increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years (P = 0.06). CONCLUSIONS—Our results indicate that in Belgium, the increasing incidence of childhood type 1 diabetes—especially for children under age 5 years—is not attributable to a global increase in disease incidence, but rather to earlier clinical manifestation. The results suggest that an environmental factor may preferentially accelerate the subclinical disease process in young diabetes-prone subjects.

OBJECTIVE—To investigate a possible association of BMI with retinopathy and neuropathy in type 1 diabetes. Retinopathy and neuropathy may not only be related to glycemic control and diabetes duration but also to blood pressure and BMI. RESEARCH DESIGN AND METHODS—A total of 592 type 1 diabetic patients without nephropathy were studied (M/F: 324/268; age: 41 ± 12 years; duration: 19 ± 11 years; HbA1c [A1C]: 7.9 ± 1.1%). Patients were subdivided according to BMI: 168 men and 146 women with BMI RESULTS—Hypertension (>130/85 mmHg) was present in 40%, retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had more retinopathy (63 vs. 45%, P < 0.0001, odds ratio [OR] = 2.1) and neuropathy (49 vs. 38%, P = 0.008, OR = 1.6) than normal-weight patients. Patients with retinopathy were older (45 ± 12 vs. 37 ± 11 years, P < 0.0001) and had a longer diabetes duration (25 ± 10 vs. 12 ± 8 years, P < 0.0001), a higher A1C (8.0 ± 1.1 vs. 7.7 ± 1.1%, P = 0.001), and a higher BMI (25.8 ± 4.1 vs. 24.7 ± 4.2 kg/m2, P = 0.001) than individuals without retinopathy. The same results are found in neuropathy. Logistic regression analysis showed that diabetes duration (β = 0.15, P < 0.0001), blood pressure (β = 0.22, P = 0.0047), and A1C (β = 0.24, P = 0.01), but not BMI, lipid levels, sex, or age, were independent risk factors for retinopathy. Likewise, duration (β = 0.05, P < 0.0001), age (β = 0.04, P = 0.0001), A1C (β = 0.35, P < 0.0001), and sex (β = 0.74, P = 0.0001) but not BMI, lipid levels, or hypertension were independently associated with neuropathy. Men had more neuropathy than women (50 vs. 34%, P < 0.0001, OR = 1.9). Leptin and adiponectin levels did not differ between individuals with or without microvascular complications. CONCLUSIONS—Retinopathy and neuropathy are more prevalent in overweight (BMI ≥25 kg/m2) type 1 diabetic subjects. However, logistic regression analysis showed that diabetes duration and A1C remain the main determinants for retinopathy and neuropathy.

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.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.Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P0.0001). 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.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.

A worldwide increase in the incidence of childhood type 1 diabetes has been observed. Because in various countries the majority of new type 1 diabetic patients are diagnosed in adulthood, we investigated whether the rising incidence of this disorder in children reflects a global increase in the incidence of diabetes or a shift toward earlier clinical presentation.The incidence of type 1 diabetes presenting before age 40 years was prospectively measured in the Antwerp district over a 12-year period (1989-2000). The completeness of ascertainment was evaluated by the capture-recapture method. Trends in incidence during the study period were analyzed by Poisson regression.The incidence of type 1 diabetes diagnosed before age 40 years remained constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per year. The incidence was similar in both sexes under age 15 years, but a marked male excess was noted for adult-onset disease, in particular after age 20 years, resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter (P = 0.001). During the 12-year observation period, there was a significant tendency toward increasing incidence under age 15 years at the expense of a decreasing incidence between ages 15 and 40 years (P = 0.025). The annual increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years (P = 0.06).Our results indicate that in Belgium, the increasing incidence of childhood type 1 diabetes-especially for children under age 5 years-is not attributable to a global increase in disease incidence, but rather to earlier clinical manifestation. The results suggest that an environmental factor may preferentially accelerate the subclinical disease process in young diabetes-prone subjects.

OBJECTIVE—Delayed gastric emptying and/or gastrointestinal symptoms occur in 30–50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15–20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA1c, thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology. RESEARCH DESIGN AND METHODS—Gastric emptying of solids and liquids (measured by 13C-octanoic acid and 13C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 ± 15 years; mean HbA1c 7.8 ± 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed. RESULTS—Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA1c level (β = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA1c, autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = −0.79, P = 0.001). CONCLUSIONS—We found that ∼50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.