The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.
The purpose of the study was to investigate bone mineral density (BMD) in children with type 1 diabetes (DM1) and to establish the relationships between BMD, physical activity, glycemic control, and markers of systemic oxidative stress and inflammation. We studied 30 children with DM1, aged 4.7-18.6 years, and 30 healthy subjects, matched by sex, age, and body mass index (BMI). Mean duration of DM1 was 5.4 +/- 3.4 years and mean glycosylated hemoglobin (HbA(1c)) level over 12 months was 9.8 +/- 1.5%. Lumbar and total bone mineral density (BMD, g/cm(2)) were measured by dual-energy X-ray absorptiometry (DXA). We calculated the apparent volumetric lumbar BMD (BMDvol, g/cm(3)) and total mineral content adjusted for age and height (BMCadj), and measured plasma intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein (hs-CRP), and urinary 8-iso-prostaglandin F(2a) (F(2)-IsoPs). Calcium (Ca) intake was assessed by questionnaire and physical activity by questionnaire and accelerometer (ActiGraph, count/h). Total BMCadj and lumbar BMDvol were significantly lower in children with DM1 than in controls (101.8 +/- 7.7 vs. 107 +/- 5.7%, P = 0.005; 0.32 +/- 0.08 vs. 0.36 +/- 0.09 g/cm(3), P = 0.05, respectively). These differences were mostly caused by the differences in boys. Plasma ICAM-1 and hs-CRP levels were significantly higher in the DM1 group compared to the controls. Ca intake and urine F(2)-IsoPs levels were similar between the groups. Diabetic boys were less active than controls (18231 +/- 6613 vs. 24145 +/- 7449 count/h, P = 0.04). In the DM1 group, lumbar BMDvol correlated inversely with urinary F(2)-IsoPs (r = -0.5; P = 0.005) and plasma ICAM-1 levels (r = -0.4; P = 0.02), and also with HbA(1c) levels after adjustment for age (r = -0.45; P < 0.05). Total BMCadj correlated inversely with HbA(1c) levels (r = -0.4; P = 0.02). We conclude that children with DM1, particularly boys, have lower BMD. Poor glycemic control, elevated markers of oxidative stress, and inflammation are associated with lower BMD.
A more pronounced expression of FOXP3 mRNA and also the number of FOXP3(+) cells (with simultaneous expression of CD25 and CD4 markers) were found in the small-bowel biopsy specimens obtained from children with CD, particularly those with coexisting T1D, compared with the FOXP3 expression in normal mucosa.
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