No abstract

This is the first study showing that AGEs are associated with human rupture-prone plaques. Furthermore, this study suggests a cascade linking inflammation, reduced GLO-1, methylglyoxal- and AGE-accumulation, and subsequent apoptosis. Thereby, AGEs may act as mediators of the progression of stable to rupture-prone plaques, opening a window towards novel treatments and biomarkers to treat cardiovascular diseases.

ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.

Summary Background Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. Aims To assess intestinal permeability at different sites of the GI tract in different subtypes of well‐characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. Methods IBS patients and HC underwent a multi‐sugar test to assess site‐specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0–5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0–24 h and 5–24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Results Ninety‐one IBS patients, i.e. 37% IBS‐D, 23% IBS‐C, 33% IBS‐M and 7% IBS‐U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS‐C and IBS‐D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS‐D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0–24 and 5–24 h sucralose/erythritol ratio between groups. Conclusions Small intestinal permeability is increased in patients with IBS‐D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS.

We found no independent adverse associations of plasma AGEs with CVD in individuals with normal glucose metabolism, impaired glucose metabolism, and T2DM.