Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

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

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.

Choroidal Thickness and Ganglion Cell Complex in Pubescent Children with Type 1 Diabetes without Diabetic Retinopathy Analyzed by Spectral Domain Optical Coherence Tomography.

AIM: To assess the retinal and choroidal thickness and ganglion cell complex (GCC) in pubescent children with type 1 diabetes (T1D) without diabetic retinopathy (DR), using spectral domain optical coherence tomography (SD-OCT). MATERIALS AND METHOD: Sixty-four right eyes of 64 subjects with T1D and 45 right eyes of 45 age-matched healthy volunteers (control group) were enrolled in this study. The mean age of the subjects and controls was 15.3 (±SD = 2.2) and 14.6 (±SD = 1.5), respectively. SD-OCT was performed using RTVue XR Avanti. Ganglion cell complex (GCC), GCC focal loss volume (FLV), GCC global loss volume (GLV), choroidal thickness (CT), foveal (FT) and parafoveal thickness (PFT), and foveal (FV) and parafoveal volume (PFV) data were analyzed. RESULTS: There was no significant difference between subjects and controls in the CT in the fovea and nasal, temporal, superior, and inferior quadrants of the macula. There were no significant correlations between CT, duration of diabetes, and HbA1C level (p = 0.272 and p = 0.197, resp.). GCC thickness did not differ significantly between the groups (p = 0.448), but there was a significant difference in FLV (p = 0.037). Significant differences between the groups were found in the PFT and PFV (p = 0.004 and p = 0.005, resp.). There was a significant negative correlation between PFT, PFV, and HbA1C level (p = 0.002 and p = 0.001, resp.). CONCLUSIONS: Choroidal thickness remains unchanged in children with T1D. Increased GCC FLV might suggest an early alteration in neuroretinal tissue. Parafoveal retinal thickness is decreased in pubescent T1D children and correlates with HbA1C level. OCT can be considered a part of noninvasive screening in children with T1D and a tool for early detection of retinal and choroidal abnormalities. Further OCT follow-up is needed to determine whether any of the discussed OCT measurements are predictive of future DR severity.

Optical coherence tomography angiography vessel density in children with type 1 diabetes.

PURPOSE: To assess the optical coherence tomography angiography (OCTA) retinal vessel density and foveal avascular zone (FAZ) in children with type 1 diabetes (T1D) and compare potential pathologic early changes in this population to healthy age-matched controls. METHODS: This study included 130 pubescent children: 94 with T1D (188 eyes) and 36 of their age-matched control group (60 eyes). OCTA was performed using AngioVue (Avanti, Optivue). FAZ area (mm2) in superficial plexus, whole superficial capillary vessel density (wsVD), fovea superficial vessel density (fsVD), parafovea superficial vessel density (psVD), whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea deep vessel density (pdVD), foveal thickness (FT) (µm) and parafoveal thickness (PFT) (µm) were taken into analysis. Among the studied patients with T1D there were assessed codependences regarding the investigated foveal and parafoveal parameters and selected potential predictors, i.e. patient's age (years), diabetes duration time (years), age of onset of the disease (years), mean level of glycated hemoglobin (HbA1C) (%), and concentration of serum creatinine (mg/dL). RESULTS: None of the abovementioned OCT and OCTA parameters was statistically significantly different between the groups. The patient's age statistically significantly did not influent any of the OCT and OCTA parameters. Yet an elevated level of HbA1C tended to reduce the parafovea superficial vessel density (p = 0.039), and parafoveal thickness (p = 0.003) and an increased serum creatinine level correlated with the decreased whole deep vessel density (p < 0.001). The parafovea deep vessel density in the diabetic patients decreased when the serum creatinine level (p = 0.008), age of onset of the disease (p = 0.028), and diabetes duration time (p = 0.014) rose. CONCLUSIONS: Vessel density, both in superficial and deep plexuses, and FAZ area are normal in pubescent children with T1D comparing to healthy subjects. An elevated level of HbA1C correlated with reduced psVD and PFT. Longitudinal observation of these young patients is needed to determine if any of these OCTA measurements are predictive of future DR severity.