Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre

Abstract

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients—The Effect of Disease Duration

“…Significantly elevated I-FABP levels in T1D patients, independent of disease duration, confirm our previous reports on epithelial damage in pediatric T1D and the utility of I-FABP as a serological marker of intestinal barrier dysfunction [ 24 ]. It is noteworthy that those substances whose concentration was not affected by the duration of the disease (IAPP, proIAPP, and I-FABP) are markers described as taking part in the pathomechanism of T1D.…”

“…In a number of studies, selected biologically active substances were indicated as contributing to the etiology (IAPP [ 16 , 31 , 32 , 33 , 34 , 35 , 36 ], proIAPP [ 17 , 18 , 37 ], I-FABP [ 24 ]), course (CST [ 38 , 39 ], ChgA [ 40 , 41 , 42 ]) or the development of various complications (neuropathy—NGF [ 43 , 44 , 45 ], cardiovascular complications—PAF [ 26 , 46 , 47 ], and cardiovascular complications and nephropatia—UMOD [ 28 , 48 , 49 ]). In the current study, we assessed the diagnostic usefulness of these indicators present in T1D patients’ sera and confirmed statistically significant differences between their concentrations in the group of children with T1D and healthy children, but only some of them (NGF, ChgA, CST and PAF) were affected by disease duration.…”

“…Therefore, the aim of our study was to assess concentrations of selected active substances such as proteins, peptides, hormones, and others, the participation of which in the pathogenesis and course of diabetes and its complications is known or postulated, and to correlate concentrations of these indicators to the duration of T1D, as well as to compare these concentrations to those of a healthy population. We analyzed the levels of islet amyloid polypeptide/amylin (IAPP) and its prohormone—proamylin (proIAPP)—substances influencing the mechanisms of carbohydrate metabolism [ 15 , 16 , 17 , 18 ]; chromogranin A (ChA)—a supposed autoantigen in T1D [ 19 , 20 , 21 ]; and the product of its proteolysis catestatin (CST) [ 22 , 23 ], intestinal fatty acid binding protein (I-FABP)—a protein responsible for increased permeability of intestinal epithelial cells, showed to be increased in children with T1D [ 24 ]. We also included in our analysis substances potentially evaluable as indicators of late complications, neurological—nerve growth factor (NGF) [ 25 ], and vascular—platelet-activating factor (PAF) [ 26 , 27 ].…”

Induced acute hyperglycemia modifies the barrier function of the intestinal epithelium by tissue inflammation and tight junction disruption resulting in hydroelectrolytic secretion in an animal model

“…The rapid increase in paracellular permeation is associated with malnutrition and absorptive disorder, which may help to explain the compromised body composition of the MetS-D group. In the clinical setting, increased intestinal permeability is reported in individuals with T1D and metabolic syndrome (28). In these patients, the presence of inflammation and disruption in the intestinal microbiota are indicated as the cause of this damage (29,30).…”

The Role of the Adrenal–Gut–Brain Axis on Comorbid Depressive Disorder Development in Diabetes

“…SCFAs are important to the maintenance of epithelial-intestinal barrier permeability, reducing the translocation of bacteria and their products from the gut to the bloodstream [47]. The reduction in the abundance of SCFA-producing bacteria in the gut microbiota is possibly involved with the breakdown of the intestinal epithelial barrier observed in diabetic patients, attested by the measure of circulating levels of lipopolysaccharide (LPS) and/or intestinal fatty acid binding protein [48,49]. Furthermore, LPS, a component of the cell wall of Gram-negative bacteria and potentially opportunistic pathogenic bacteria found in the gut microbiota of diabetic patients, enhanced intestinal permeability in vitro and in vivo [50,51].…”