Aim: To test whether a gluten‐free diet (GFD) is associated with the deceleration of the decline in beta‐cell capacity in non‐coeliac children with recently diagnosed type 1 diabetes. Methods: Forty‐five children (aged 10.2 ± 3.3 years) were recruited into a self‐selected intervention trial: 26 started with a GFD within a median of 38 days postonset, whereas 19 remained on a standard diet. The main outcomes were the decline in C‐peptide area under the curve (AUC) in mixed‐meal tolerance tests (MMTTs) at 6 and 12 months relative to 1 month after diabetes onset and the difference in insulin dose, insulin dose‐adjusted A1c (IDAA1c) and HbA1c assessed every 3 months. The adherence to the GFD was verified by immunoreactive gluten in the stool and by food questionnaires at every visit. Quality of life (QoL) questionnaires were administered to the participants at the end of the intervention at 12 months. The data were analysed as per protocol (in 39 subjects who duly completed the whole follow‐up: 20 in the GFD group, 19 in the control group) by linear and longitudinal regression models adjusted for sex, age and baseline variables. Results: At 12 months, the difference in C‐peptide AUC between subjects in the GFD group and controls was 205 pmol/L (95% CI ‐223 to 633; P = 0.34) in a model adjusted for age, sex and body weight, and for baseline insulin dose, MMTT C‐peptide AUC and HbA1c assessed at 1 month after diagnosis. In a longitudinal analysis of all three time points adjusted for age, sex and body weight, C‐peptide declined more slowly in the GFD group than in controls, with the difference in trends being 409 pmol/L/year ( P = 0.04). The GFD group had a marginally lower insulin dose (by 0.15 U/kg/day; P = 0.07), a lower IDAA1c (by 1.37; P = 0.01) and a lower mean HbA1c (by 0.7% [7.8 mmol/mol]; P = 0.02) than those of the controls at 12 months. There was no appreciable difference between the groups in daily carbohydrate intake ( P = 0.49) or in the QoL reported by the patients ( P = 0.70) and their parents/caregivers ( P = 0.59). Conclusions: A GFD maintained over the first year after type 1 diabetes diagnosis was associated with better HbA1c and a prolonged partial remission period. There was a hint of slower C‐peptide decline but the association was not strong enough to make definite conclusions.

Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten.Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring.Methods. Nonobese diabetic mice were divided into 7 groups to receive combinations of gluten-free and standard diet before, during, or after pregnancy. Diabetes incidence in offspring was followed in each group (n=16–27) for 310 days. Insulitis score and intestinal expression of T-cell transcription factors (RT-QPCR) were evaluated in animals from the different diet groups.Results. If mothers were fed a gluten-free diet only during pregnancy, the development of autoimmune diabetes in offspring was almost completely prevented with an incidence reduction from 62.5% in gluten-consuming mice to 8.3% (p<0.0001) in the gluten-free group. The islets of Langerhans were less infiltrated (p<0.001) and the intestinal expression of RORγt (Th17) (p<0.0001) reduced in mice whose mothers were Gluten-free during pregnancy.Conclusion. A gluten-free diet exclusively during pregnancy efficiently prevents autoimmune diabetes development in offspring and reduces insulitis and intestinal expression of RORγt (Th17).

Tolerogenic DCs (tolDCs) are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D). T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65), that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD)-severe combined immunodeficiency (NOD-SCID) recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein—ovalbumin (OVA). The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II) and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ) did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. application. These data document that mechanisms by which tolDCs operate in vivo require much better understanding for improving efficacy of this promising cell therapy, especially in the presence of an antigen, e.g., GAD65.