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Background and Aims: The effect of estrogens is mediated by activation of estrogen receptors (ERs), which are expressed in many tissues. Because ER-α gene polymorphisms may exert different effects in childhood, in the present study we analyzed associations between the IVS1 -397T>C polymorphism and indicators of inflammatory response as well as late complications in boys with type 1 diabetes mellitus (DM1)., Methods and Results: We examined 108 young boys with DM1 and 64 healthy age-matched control individuals. ER-α genotyping, as well as the CRP and IL-6 serum level and blood pressure, was analyzed. In our study boys with CC genotype had lower blood pressure and IL-6 and CRP serum levels. Similar results were obtained for DM1 boys with microvascular complications - the blood pressure and serum level of IL-6, but not CRP, were still lower in the CC patients., Conclusions: Our findings suggest that the presence of -397T allele may indicate macro- and microvascular complications in DM1 boys, before the occurrence of first clinical symptoms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The study aimed to investigate the influence of estrogen receptor α (ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes., Methods: 152 young regularly menstruating girls with diagnosed type 1 diabetes and 84 young, healthy menstruating girls were recruited. ER-α genotyping was carried out by PCR. Serum concentrations of 17β-estradiol, as well as IL-6, TNF-α, VEGF, and IL-10, were measured. CD4(+)Foxp3(+) TH17 cells were isolated and analyzed by flow cytometry., Results: Type 1 diabetic girls carrying TT genotype were characterized by the lowest serum estradiol level and IL-10 and highest IL-6, TNF-α, and VEGF. The association between the level of certain cytokine and the genetic variant of estrogen receptor α polymorphism was analyzed. Frequencies of CD4(+)Foxp3(+) TH17 cells were also enhanced in TT bearing girls with type 1 diabetes and correlated with the level of analyzed cytokines. In addition, the correlation between serum estradiol level and cytokine concentrations was observed., Conclusions: We propose that TT variant of estrogen receptor α polymorphism may be associated with enhanced inflammatory response, which in turn may lead to acceleration of diabetic retino- and nephropathy in girls with type 1 diabetes. This finding may help the physicians to predict the onset and progression of diabetic microvascular complications.

Background/Objective: Recent studies suggest that uric acid (UA) is a mediator of diabetic nephropathy. We hypothesized that serum UA would associate with the prevalence of diabetic nephropathy in youth with type 1 diabetes (T1D), and that this relationship would differ by sex. Methods: We examined 120 young boys and the same number of girls with T1D. C‐reactive protein (CRP), interleukin‐6 (IL‐6), interleukin‐10 (IL‐10), tumor necrosis factor α (TNF‐α), UA, cystatin C serum concentrations, albumin excretion rate and blood pressure were also analyzed. Results: T1D boys had higher serum UA and creatinine concentration, as well as albumin excretion rate and estimated glomerular filtration rate than T1D girls. Moreover, newly diagnosed nephropathy was more common in male subjects in comparison to female patients. Only in T1D boys serum UA was positively correlated with concentrations of subclinical inflammatory markers (CRP, IL‐6, TNF‐α), the indicators of renal function (albumin excretion rate, serum cystatin C level), blood pressure and negatively correlated with anti‐inflammatory IL‐10. In addition, only in T1D girls serum UA concentration was negatively correlated with hemoglobin A1c. Conclusions: Serum UA is associated with nephropathy prevalence, albeit only in boys with T1D and may be an important risk factor for predicting diabetes‐related cardiorenal complications in these patients. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to assess the relationship between the CCR5-Δ32 polymorphism and the risk of diabetic retinopathy (DR) in patients with DM1. Methods We examined 420 patients and 350 healthy controls. The analysis concerned CCR5-Δ32 polymorphism as well as levels of serum inflammatory markers (CRP, TNF-α), adhesion molecules (VCAM, ICAM-1, ICAM-3) and CCR5 ligand (MCP-1). Results We found a negative association between DM1 and Δ32 allele. Moreover, the frequency of Δ32 allele was higher in a group with DR in comparison to control subjects without this complication. We also found that Δ32 carriers had the highest levels of: HbA1c, inflammatory markers, adhesion molecules and CCR5 ligand. Conclusions The findings of our studies suggest that the CCR5-Δ32 polymorphism is associated with DM1 such that the Δ32 allele protects against the development of DM1 and increases the risk of DR in patients who have already developed the disease. [ABSTRACT FROM AUTHOR]