ABSTRACT
AIM: Gluten-free diet has shown promising effects in preventing type 1 diabetes (T1D) in animals as well as beneficial effects on the immune system. Gluten-free diet at diabetes onset may alter the natural course and outcome of autoimmune diseases such as T1D. METHODS: In a 12-month study, 15 children newly diagnosed with T1D were instructed to follow a gluten-free diet. Questionnaires were used to evaluate adherence to the gluten-free diet. Partial remission (PR) was defined by insulin dose-adjusted A1c (IDAA1c) ≤9 or stimulated C-peptide (SCP) >300 pmol/L measured 90 min after a liquid mixed meal at the inclusion, six and 12 months after onset. The intervention group was compared with two previous cohorts. Linear mixed models were used to estimate differences between cohorts. RESULTS: After 6 months, more children on a gluten-free diet tended to have SCP values above 300 pmol/L compared to the European cohort (p = 0.08). The adherence to a gluten-free diet decreased during the 12-month study period. After 1 year there was no difference in SCP levels or percentage in remission according to SCP (p > 0.1). Three times as many children were still in PR based on IDAA1c (p < 0.05). Twelve months after onset HbA1c were 21 % lower and IDAA1c >1 unit lower in the cohort on a gluten-free diet compared to the two previous cohorts (p < 0.001). CONCLUSION: Gluten-free diet is feasible in highly motivated families and is associated with a significantly better outcome as assessed by HbA1c and IDAA1c. This finding needs confirmation in a randomized trial including screening for quality of life. (Clinicaltrials.gov number NCT02284815).
ABSTRACT
Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy children. Fifty-six established T1D SNPs and 97 other candidate immunity SNPs were typed in 419 children carrying the T1D high-risk genotype, HLA-DR4-DQ8/DR3-DQ2 genotype, and 373 children without this genotype. Enteroviral RNA was detected using real-time polymerase chain reaction, with primers detecting essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541 (C1QTNF6/SSTR3/RAC2) (enterovirus frequency: CC 7.8%, CT 9.7%, TT 9.4%, RR = 1.13, overall p = 3.6E-02), followed by TLR8 (rs2407992) (p = 3.8E-02), TLR3 (1914926) (p = 4.9E-02), and two other T1D SNPs (IFIH1 rs3747517, p = 4.9E-02 and PTPN22, rs2476601, p = 5.3E-02). However, the quantile-quantile plot of p-values with confidence intervals for all 153 SNPs did not reveal clear evidence for rejection of the complete null hypothesis. Among a number of SNPs in candidate genes, we found no evidence for strong associations with enterovirus presence in stool samples from Norwegian children.
Subject(s)
Enterovirus Infections/genetics , Genetic Predisposition to Disease , Child, Preschool , Enterovirus/isolation & purification , Enterovirus Infections/epidemiology , Feces/virology , Female , Genetic Association Studies , Humans , Infant , Longitudinal Studies , Male , Norway , Polymorphism, Single Nucleotide , RNA, Viral/analysis , RNA, Viral/genetics , Real-Time Polymerase Chain ReactionABSTRACT
Type 1 diabetes is a disease with serious personal and socioeconomic consequences that has attracted the attention of modellers recently. But as models of this disease tend to be complicated, there has been only limited mathematical analysis to date. Here we address this problem by providing a bifurcation analysis of a previously published mathematical model for the early stages of type 1 diabetes in diabetes-prone NOD mice, which is based on the data available in the literature. We also show positivity and the existence of a family of attracting trapping regions in the positive 5D cone, converging towards a smaller trapping region, which is the intersection over the family. All these trapping regions are compact sets, and thus, practical weak persistence is guaranteed. We conclude our analysis by proposing 4 novel treatment strategies: increasing the phagocytic ability of resting macrophages or activated macrophages, increasing the phagocytic ability of resting and activated macrophages simultaneously and lastly, adding additional macrophages to the site of inflammation. The latter seems counter-intuitive at first glance, but nevertheless it appears to be the most promising, as evidenced by recent results.
