Genetic Association Study of IL2RA, IFIH1, and CTLA-4 Polymorphisms With Autoimmune Thyroid Diseases and Type 1 Diabetes.

Autoimmune thyroid diseases (AITDs) which include Graves' disease (GD) and Hashimoto's thyroiditis (HT) as well as type 1 diabetes (T1D) are common autoimmune disorders in children. Many genes are involved in the modulation of the immune system and their polymorphisms might predispose to autoimmune diseases development. According to the literature genes encoding IL2RA (alpha subunit of Interleukin 2 receptor), IFIH1 (Interferon induced with helicase C domain 1) and CTLA-4 (cytotoxic T cell antigen 4) might be associated with autoimmune diseases pathogenesis. The aim of the study was to assess the association of chosen single nucleotide polymorphisms (SNPs) of IL2RA, IFIH1, and CTLA-4 genes in the group of Polish children with AITDs and in children with T1D. We analyzed single nucleotide polymorphisms (SNPs) in the IL2RA region (rs7093069), IFIH1 region (rs1990760) and CTLA-4 region (rs231775) in group of Polish children and adolescents with type 1 diabetes (n = 194) and autoimmune thyroid diseases (GD n = 170, HT n = 81) and healthy age and sex matched controls for comparison (n = 110). There were significant differences observed between T1D patients and control group in alleles of IL2RA (rs7093069 T > C) and CTLA-4 (rs231775 G > A). In addition, the study revealed T/T genotype at the IL2RA locus (rs7093069) and G/G genotype at the CTLA-4 locus (rs231775) to be statistically significant more frequent in children with T1D. Moreover, genotypes C/T and T/T at the IFIH1 locus (rs1990760) were significantly more frequent in patients with T1D than in controls. We observed no significant differences between AITD patients and a control group in analyzed SNPs. In conclusion, we detected that each allele T of rs7093069 SNP at the IL2RA locus and G allele of rs231775 SNP at the CTLA-4 locus as well as C/T and T/T genotypes of rs1990760 SNP at the IFIH1 locus are predisposing in terms of T1D development. Thereby, we confirmed that IL2RA, IFIH1, and CTLA-4 gene locus have a role in T1D susceptibility. The analysis of selected SNPs revealed no association with AITDs in a group of Polish children and adolescents.

Increasing Co-occurrence of Additional Autoimmune Disorders at Diabetes Type 1 Onset Among Children and Adolescents Diagnosed in Years 2010-2018-Single-Center Study.

Objectives: The prevalence of type 1 diabetes mellitus (T1D) in children is growing, but its relation to other autoimmune disorders that coexist since the onset of diabetes is not recognized. The objective of this study was to assess the incidence of T1D and the prevalence of autoimmune illnesses additionally coexisting since the diabetes mellitus onset in children during a period of 9 years' observation. Methods: In this retrospective study, the incidence rate (IR) of the T1D was calculated as the total number of all cases that were newly diagnosed per 100,000 population people between 0 and 18 years of age. The selected age groups (0-4, 5-9, 10-14, and 15-18 years) were examined, respectively. The studied group included 493 children (264 [53.55%] boys) between 0 and 18 years old newly diagnosed with T1D in one of the Polish centers in the years 2010-2018. Other autoimmune illnesses diagnoses were obtained from medical records taken from the first hospital treatment, when T1D was recognized. Results: The annual standardized IR of T1D increased from 19.2/100,000 in year 2010 to 31.7/100,000 in 2018 (1.7-fold over 9 years' observation), with an increase in the incidence rate ratio (IRR) by 4% per year. The highest growth in IR was recorded in 5- to 9-year-olds (from 19.61 in 2010 to 43.45 in 2018). In 61 (12.4%) of the studied group, at least one additional autoimmune disease was diagnosed. The prevalence doubled from 10.4% in the year 2010 to 20.8% in the year 2018. Autoimmune thyroid illnesses were found in 37 children (7.5%); their incidence increased from 6.3% to almost 2-fold, 12.5%, in 2018. In 26 children (5.3%), celiac disease was recognized; the prevalence increased from 4.2 to 9.8% in the study period. The prevalence of additional autoimmune thyroid disease was higher in glutamic acid decarboxylase-positive antibodies (χ2 = 3.4, p = 0.04) patients, the oldest age group (15-18 years) (χ2 =7.1, p = 0.06), and in girls (χ2 =7.1, p = 0.007). Conclusions:The standardized IR of T1D in children increased 1.7-fold over the 9-year observation period, and IRR increased 4% per year. Additional autoimmunity represents a significant comorbidity in patients with new-onset T1D. The number of children diagnosed with additional autoimmune diseases that accompany T1D is rapidly growing in all age groups throughout recent years.

Five-year observation of the relationship between body mass index and glycated hemoglobin in children with Type 1 diabetes mellitus.

BACKGROUND: Poor metabolic control is a well-recognized risk factor for cardiovascular disease. However, the relationship between such factor as body weight and metabolic control in children with diabetes mellitus type 1 (DM1) is unclear. The aim of this study was to examine the relationships between body weight, age, metabolic control, sex, and form of insulin therapy in children with DM1. METHODS: This was a retrospective study of children with DM1 treated at one diabetes center for a minimum of 5 years since diagnosis. RESULTS: Median body mass index standard deviation score (BMI-SDS) increased annually (p = .0042) on average 0.08 ± 0.27 per year throughout the observation. As well HbA1c and daily dose insulin increased annually (p < .0001; p < .0001, respectively) on average by 0.43 ± 0.79 and by 0.13 ± 0.17 per year. Percentage of good metabolic control - HbA1c cut-off of 6.5% - gradually worsened in all patients over the 5 years, with a higher percentage of girls experiencing poor metabolic control (84.48% of girls vs. 77.87% of boys; p = .01895). No correlation between BMI-SDS and metabolic control (HbA1c) was found (R = 0.09, p = .60). CONCLUSIONS: Body weight appears to be more affected by non-diabetic factors (e.g. irregular eating and sedentary lifestyle) than by the clinical course of diabetes. Metabolic control and body weight must be maintained in all children with DM1 (males and females) to reduce their future risk of cardiovascular disease.