Context: Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3-to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients.Synthesis: Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. Conclusion:The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.

The autoimmune attack in type 1 diabetes is not only targeted to β cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA‐IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, β‐cell antibody status (ICA, GADA, IA2A) and HLA‐DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 ± 16 years; duration: 9 ± 8 years) were tested for ICA, PCA, AAA and EmA‐IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase‐65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA‐IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (β = − 1·15, P = 0·002), age (β = 0·02, P = 0·01) and GADA + (β = 1·06, P = 0·02), but not by HLA‐DQ type or IA2A status. Dysthyroidism (P < 0·0001) was more frequent in aTPO + subjects. PCA status was determined by age (β = 0·03, P = 0·002). We also observed an association between PCA + and GADA + (OR = 1·9, P = 0·049), aTPO + (OR = 1·9, P = 0·04) and HLA DQA1*0501‐DQB1*0301 status (OR = 2·4, P = 0·045). Iron deficiency anaemia (OR = 3·0, P = 0·003) and pernicious anaemia (OR = 40, P < 0·0001) were more frequent in PCA + subjects. EmA‐IgA + was linked to HLA DQA1*0501‐DQB1*0201 + (OR = 7·5, P = 0·039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501‐DQB1*0301 and EmA‐IgA + with HLA DQA1*0501‐DQB1*0201.

Demographic and biological data were collected from all Caucasian Type 1 diabetic patients (n = 279) who were recruited at clinical onset by the Belgian Diabetes Registry over 34 months. The male/female ratio was significantly higher for onset between age 20 and 40 years (2.4) than before age 20 years (1.0); no age-or sex-differences were noticed in serum fructosamine concentration. Total and high concentrations of insulin autoantibodies and islet cell antibodies were preferentially associated with the HLA DQA1*0301-DQB1*0302 susceptibility haplotype. The occurrence of both types of antibodies was also correlated, irrespective of haplotype. At onset before age 10 years, the high risk genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 was more prevalent than all other DQA1-DQB1 genotypes taken together, leading to a higher prevalence of the DQA1*0301-DQB1*0302 haplotype in this age group (75%) than in the 10-39 years age group (54%). Under age 10 years, the presence of DQA1*0301-DQB1*0302 was strongly associated with insulin autoantibodies (90%) and islet cell autoantibodies (92% with 85% of high titre), whereas patients without this haplotype were less frequently positive for insulin autoantibodies (31%) or islet cell autoantibodies (38% high titre). In the group with onset at age 10-39 years, the DQA1*0301-DQB1*0302 haplotype presented a lower association with insulin autoantibodies (approximately 40%) and islet cell autoantibodies (50 to 65% high titre), prevalences which no longer differed from those in subjects lacking this haplotype.(ABSTRACT TRUNCATED AT 250 WORDS)

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 Ϯ 12 years; duration: 19 Ϯ 11 years; HbA 1c [A1C]: 7.9 Ϯ 1.1%). Patients were subdivided according to BMI: 168 men and 146 women with BMI Ͻ25 kg/m 2 , and 156 men and 122 women with BMI Ն25 kg/m 2 . Retinopathy was examined by fundoscopy and neuropathy by electromyography.RESULTS -Hypertension (Ͼ130/85 mmHg) was present in 40%, retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had more retinopathy (63 vs. 45%, P Ͻ 0.0001, odds ratio [OR] ϭ 2.1) and neuropathy (49 vs. 38%, P ϭ 0.008, OR ϭ 1.6) than normal-weight patients. Patients with retinopathy were older (45 Ϯ 12 vs. 37 Ϯ 11 years, P Ͻ 0.0001) and had a longer diabetes duration (25 Ϯ 10 vs. 12 Ϯ 8 years, P Ͻ 0.0001), a higher A1C (8.0 Ϯ 1.1 vs. 7.7 Ϯ 1.1%, P ϭ 0.001), and a higher BMI (25.8 Ϯ 4.1 vs. 24.7 Ϯ 4.2 kg/m 2 , P ϭ 0.001) than individuals without retinopathy. The same results are found in neuropathy. Logistic regression analysis showed that diabetes duration (␤ ϭ 0.15, P Ͻ 0.0001), blood pressure (␤ ϭ 0.22, P ϭ 0.0047), and A1C (␤ ϭ 0.24, P ϭ 0.01), but not BMI, lipid levels, sex, or age, were independent risk factors for retinopathy. Likewise, duration (␤ ϭ 0.05, P Ͻ 0.0001), age (␤ ϭ 0.04, P ϭ 0.0001), A1C (␤ ϭ 0.35, P Ͻ 0.0001), and sex (␤ ϭ 0.74, P ϭ 0.0001) but not BMI, lipid levels, or hypertension were independently associated with neuropathy. Men had more neuropathy than women (50 vs. 34%, P Ͻ 0.0001, OR ϭ 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 Ն25 kg/m 2 ) type 1 diabetic subjects. However, logistic regression analysis showed that diabetes duration and A1C remain the main determinants for retinopathy and neuropathy. Diabetes Care 28:1649 -1655, 2005O verweight (BMI Ն25 kg/m 2 ) and obesity (BMI Ն30 kg/m 2 ) are becoming increasingly prevalent in the industrialized world (1), not only in type 2 but also in type 1 diabetic patients (2-4). Besides physical inactivity, intensive insulin therapy to obtain good metabolic control to reduce complications is associated with weight gain (4,5). The relationship between metabolic control and the development of chronic complications (retinopathy, neuropathy, and nephropathy) is a primary concern of clinicians. Factors involved in the development of vascular complications of diabetes include long diabetes duration, poor glycemic control, smoking, hypertension, and dyslipidemia, but the role of body weight/BMI is unclear.Retinopathy may not only be related to glycemic control and diabetes duration but also to blood pressure and BMI for patients with type 2 diabetes, as was sho...