Celiac disease associated antibodies in persons with latent autoimmune diabetes of adult and type 2 diabetes.

BACKGROUND: Celiac Disease (CD) is present in 1-16.4% of patients with type 1 diabetes mellitus. The most important serological markers of CD are anti-endomysial (EMA), anti-tissue transglutaminase (tTGA) and antigliadin antibodies (AGA). AIM/HYPOTHESIS: The objective of this work is to determine the frequency of tTGA and/or AGA in latent autoimmune diabetes of adult (LADA) and subjects with type 2 diabetes (T2DM), as well as to evaluate their relation with several clinical and biochemical characteristics. SUBJECTS AND METHODS: Forty three subjects with LADA and 99 with T2DM were studied. The presence of AGA, tTGA was determined in the sera of these patients. The variables: sex, age, duration of diabetes, treatment, body mass index (BMI) and fasting blood glucose concentration were also recorded. RESULTS: No differences were found in the frequency of celiac disease associated antibodies between LADA and T2DM subjects. The presence of celiac disease related antibodies was more frequent in patients with a normal or low BMI. CONCLUSIONS: Celiac disease does not seem to be related with pancreatic autoimmunity in type 2 diabetes. Celiac disease causes a decrease of body mass index in type 2 diabetes while pancreatic islet autoimmunity in this entity masks this effect.

Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16.

AIMS/HYPOTHESIS: To determine whether the emergent infection by echovirus 16 that occurred in Cuba during the year 2000 was related to the presence of Type 1 diabetes associated autoantibodies. METHODS: The presence of ICA, IAA, GADA, IA2 antibodies and neutralizing antibodies (NtAb) to echovirus 16 were determined in sera from 38 infected children and adolescents and 80 control subjects, matched in sex, age, local residence and time of sample collection. RESULTS: The occurrence of a large-scale echovirus 16 epidemic was associated with the appearance of humoral autoimmune markers of Type 1 diabetes, especially for ICA, IAA and GADA. In the convalescent stage, ICA, IAA and GADA seroconversion was shown in 92.1%, 44.7% and 28.9% of echovirus 16 infected subjects. None of the 80 uninfected subjects had ICA or IAA, while one was GADA positive. ICA, IAA and GADA frequency was higher in the convalescent than in the acute stage (p<0.0005). A strong positive correlation was found between the NtAb to echovirus 16 and ICA titres in both acute and convalescent stage (r=0.91; p<0.0001, r=0.55; p=0.0003 respectively). CONCLUSION/INTERPRETATION: This work provides evidence of an association between echovirus 16 infection and the presence of Type 1 diabetes related antibodies (ICA, IAA and GADA). Our data show that the echovirus 16 infection might be capable of inducing a process of autoimmune beta-cell damage and support the hypothesis that enterovirus infections are important risk factors for the development of Type 1 diabetes.

Echovirus 4 and type 1 diabetes mellitus.

AIMS/HYPOTHESIS: To determine the association between exposure to enteroviruses and Type 1 diabetes. METHODS: We measured neutralizing antibodies to the following enteroviruses: Coxsackievirus CA9, CB1, CB2, CB3, CB4, CB5, CB6, and Echovirus E4, E6, E9, E11 in the sera of (1) Type 1 diabetic patients at diagnosis (n = 33), (2) healthy offspring of parents with Type 1 diabetes without islet cell antibodies (ICA) (n = 43) and (3) normal controls (n = 57). All subjects were less than 20 years old. We performed the neutralization test determining the cytopathogenic effect on Vero cells. HLA DR serotyping was also performed in Group 2. RESULTS: Type 1 diabetic patients showed a higher frequency (21.2%, p < 0.01) of neutralizing antibodies to E4 in relation to controls (1.8%), although there were no differences comparing with offspring of Type 1 diabetic patients (20.9%). Healthy offspring carrying Type 1 diabetes HLA DR susceptibility genes were also exposed to E4 (15.0%). High frequencies of neutralizing antibodies to most enteroviruses were found in the control group. CONCLUSION: This study shows the association between Type 1 diabetes and the presence of neutralizing antibodies to Echovirus 4, suggesting the possible participation of this virus as an environmental trigger of this autoimmune disease. Interestingly, our population displays high frequencies of exposure to enterovirus (including CB4) although the incidence for Type 1 diabetes is low (2.9 per 100,000 inhabitants).

Glycolipids as the major autoantigens of cytoplasmatic islet cell antibodies.

It has been recently suggested that pancreatic glycolipidic extracts and acidic glycolipid fractions are able to block the binding of ICA to frozen sections of human pancreas. We study the prevalence of blocking effect by the upper-phase from human pancreatic glycolipid extracts (PGE) in thirty-eight sera ICA positive from seventeen IDDM patients and twenty-one first relatives of type 1 diabetics. Total inhibition was found in 82% and 76% insulin dependent diabetes mellitus patients and first relatives of type 1 diabetics respectively. Partial and no inhibition of ICA+ sera was seen in 6%, 12% of type 1 diabetics and 19%, 5% of the first degree relatives of type 1 diabetics respectively. Our study suggests that there is heterogeneity of cytoplasmatic islet cell antibodies and that glycolipids are the major autoantigen of ICA.