An effective prevention from T1D is presently unknown. The primary objective of this study is to test whether gluten-free diet (GFD) instituted in children shortly after T1D onset can decelerate the decline in beta cell function as compared to age and gender-matched controls. Our hypothesis is that GFD since diabetes onset will help preserve the beta cell mass and function, which will be observable by a reduction in C-peptide AUC decline in mixed-meal tolerance test relative to the normal diet group. Secondary objectives are: 1) to investigate whether GFD modifies the immune parameters; 2) to assess the differences in fecal microbiome between children on normal diet and children on GFD, 3) to investigate the effect of gut microbiome transfer from children on GFD with the extremes of beta-cell loss to germ-free NOD mice in an attempt to replicate the difference in response to GFD observed in humans. The identification of a nutritional factor in T1D would - upon proper replication in other studies - open avenues towards implementing a simple and well established T1D intervention.

Úsilí o nalezení účinného preventivního nástroje diabetu 1. typu (T1D) dosud selhává. Kazuistická sdělení ukazují, že bezlepková dieta (GFD) může vést ke kompletní remisi diabetu 1. typu v období bezprostředně po jeho manifestaci, účinnost GFD na zmírnění průběhu autoimunitní inzulitídy byla prokázána též na myším modelu. Primárním cílem projektu je prokázat, zda GFD zahájená bezprostředně po manifestaci T1D ovlivní reziduální kapacitu beta buněk v porovnání s kontrolní skupinou. Testovanou hypotézou je možnost prezervace beta buněk (vyjádřená pomocí poklesu AUC C-peptidu při testu smíšenou stravou) zavedením GFD. Sekundárními cíli je posouzení efektu GFD na imunitní systém a na střevní mikrobiom. Vliv specifické kombinace mikrobiálního osídlení střeva bude následně testován na modelu germ-free NOD myší. Průkaz účinnosti GFD na kapacitu reziduálních beta buněk by otevřel nové možnosti prevence T1D.

• MeSH
• beta-buňky MeSH
• bezlepková dieta MeSH
• diabetes mellitus 1. typu dietoterapie   prevence a kontrola   MeSH
• dítě MeSH
• experimentální diabetes mellitus MeSH
• gnotobiologické modely MeSH
• imunita MeSH
• lidé MeSH
• myši inbrední NOD MeSH
• střevní mikroflóra MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• hodnotící studie MeSH

• Konspekt
• Pediatrie
• NLK Obory
• pediatrie
• diabetologie
• nutriční terapie, dietoterapie a výživa
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

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.

• MeSH
• bezlepková dieta MeSH
• C-peptid MeSH
• celiakie * MeSH
• diabetes mellitus 1. typu * farmakoterapie   MeSH
• dítě MeSH
• inzulin MeSH
• kvalita života MeSH
• lidé MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Tolerogenic dendritic cells (tolDCs) are explored as a promising standalone or combination therapy in type 1 diabetes (T1D). The therapeutic application of tolDCs, including in human trials, has been tested also in other autoimmune diseases, however, T1D displays some unique features. In addition, unlike in several disease-induced animal models of autoimmune diseases, the prevalent animal model for T1D, the NOD mouse, develops diabetes spontaneously. This review compares evidence of various tolDCs approaches obtained from animal (mainly NOD) models of T1D with a focus on parameters of this cell-based therapy such as protocols of tolDC preparation, antigen-specific vs. unspecific approaches, doses of tolDCs and/or autoantigens, application schemes, application routes, the migration of tolDCs as well as their preventive, early pre-onset intervention or curative effects. This review also discusses perspectives of tolDC therapy and areas of preclinical research that are in need of better clarification in animal models in a quest for effective and optimal tolDC therapies of T1D in humans.

• MeSH
• dendritické buňky imunologie   transplantace   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední NOD MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

AIMS/HYPOTHESIS: This study aimed to assess the ability of human gut microbiota to delay the onset of type 1 diabetes when transferred into germ-free NOD mice. METHODS: Two children with rapid and three children with slow beta cell function loss (as assessed by C-peptide AUC change in the mixed-meal tolerance tests performed 1 and 12 months after type 1 diabetes onset), participating in an ongoing trial with gluten-free diet, donated faeces, which were transferred into germ-free NOD mice. The mice were subsequently followed for diabetes incidence. RESULTS: The bacterial profiles of bacteriome-humanised mice had significantly (p < 10-5) lower alpha diversity than the donor material, with marked shifts in ratios between the main phyla. Diabetes onset was significantly delayed in all bacteriome-humanised colonies vs germ-free NOD mice, but the pace of beta cell loss was not transferable to the mouse model. CONCLUSIONS/INTERPRETATION: Germ-free NOD mice colonised with human gut microbiome are able to adopt a large proportion of transferred bacterial content, although the ratios of main phyla are reproduced only suboptimally. The recipient mice did not replicate the phenotype of the stool donor in relation to the pace towards type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02867436.

• MeSH
• diabetes mellitus 1. typu mikrobiologie   terapie   MeSH
• feces mikrobiologie   MeSH
• lidé MeSH
• mikrobiota fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední NOD MeSH
• myši MeSH
• progrese nemoci MeSH
• střevní mikroflóra fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH